One Heart Magazine_HRS Scientific Sessions Supplement

ONE HEART MAGAZINE HRS Scientific Sessions Supplement • May 7-10, 2014

PROOF

THE FIRST ROUND WAS TOUGH ENOUGH.

I’D RATHER NOT GO A SECOND ROUND.

PROOF Proven market experience Effient is included in the Guidelines for UA/NSTEMI and STEMI patients undergoing PCI

1

2013 ACCF*/AHA† STEMI Guideline2,3 2012 ACCF/AHA Guideline Update for UA/NSTEMI4,5 2011 ACCF/AHA/SCAI‡ Guideline for PCI6,7

For more information, call your Effient representative or visit EffientHCP.com today.

2

ONE HEART MAGAZINE

HRS SCIENTIFIC SESSIONS SUPPLEMENT 2014

www.HeartbeatSavesLives.org

Effient® (prasugrel) is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: [1] patients with unstable angina (UA) or non–STelevation myocardial infarction (NSTEMI); [2] patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. The loading dose (LD) of Effient is 60 mg and the maintenance dose (MD) is 10 mg once daily. Effient is available in 5-mg and 10-mg tablets.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS Effient is contraindicated in patients with active pathological bleeding, such as from a peptic ulcer or intracranial hemorrhage (ICH), or a history of transient ischemic attack (TIA) or stroke, and in patients with hypersensitivity to prasugrel or any component of the product

WARNING: BLEEDING RISK Effient® (prasugrel) can cause significant, sometimes fatal, bleeding.

Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke.

In patients ≥75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction [MI]) where its effect appears to be greater and its use may be considered.

Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery.

Additional risk factors for bleeding include: body weight <60 kg propensity to bleed concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs]) Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient.

If possible, manage bleeding without discontinuing Effient.

Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events.

WARNINGS AND PRECAUTIONS Patients who experience a stroke or TIA while on Effient generally should have therapy discontinued. Effient should also be discontinued for active bleeding and elective surgery Premature discontinuation of Effient increases risk of stent thrombosis, MI, and death Thrombotic thrombocytopenic purpura (TTP), a rare but serious condition that can be fatal, has been reported with Effient, sometimes after a brief exposure (<2 weeks), and requires urgent treatment, including plasmapheresis Hypersensitivity, including angioedema, has been reported in patients receiving Effient, including patients with a history of hypersensitivity reaction to other thienopyridines

PROOF ADVERSE REACTIONS

Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction

Please see Brief Summary of Prescribing Information, including Boxed Warning regarding bleeding risk, on subsequent pages. *American College of Cardiology Foundation. †American Heart Association. ‡Society for Cardiovascular Angiography and Interventions.

References: 1. Data on file: #EFF20130124a: DSI/Lilly. 2. O’Gara PT, Kushner FG, Ascheim DD, et al. Circulation. 2013;127:e362-e425. 3. O’Gara PT, Kushner FG, Ascheim DD, et al. J Am Coll Cardiol. 2013;61:e78-e140. 4. Jneid H, Anderson JL, Wright RS, et al. Circulation. 2012;126:875-910. 5. Jneid H, Anderson JL, Wright RS, et al.

J Am Coll Cardiol. 2012;60:653-689. 6. Levine GN, Bates ER, Blankenship JC, et al. Circulation. 2011;124:e574-e651. 7. Levine GN, Bates ER, Blankenship JC, et al. J Am Coll Cardiol. 2011;58:e44-e122.

Effient and the Effient logo are registered trademarks of Eli Lilly and Company.

Copyright © 2013 Daiichi Sankyo, Inc. and Lilly USA, LLC. All Rights Reserved.

PG84132. PGHCPISI03Oct2011. Printed in USA. May 2013.

®

www.HeartbeatSavesLives.org

HRS SCIENTIFIC SESSIONS SUPPLEMENT 2014

ONE HEART MAGAZINE

3

BRIEF SUMMARY: Please see Full Prescribing Information for additional information about Effient.

WARNING: BLEEDING RISK Effient can cause significant, sometimes fatal, bleeding [see Warnings and Precautions (5.1 and 5.2) and Adverse Reactions (6.1)].

Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke [see Contraindications (4.1 and 4.2)].

In patients ≥75 years of age, Effient is generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in highrisk situations (patients with diabetes or a history of prior MI) where its effect appears to be greater and its use may be considered [see Use in Specific Populations (8.5)].

Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery.

Additional risk factors for bleeding include: • body weight <60 kg • propensity to bleed • concomitant use of medications that increase the risk of bleeding (e.g., warfarin, heparin, fibrinolytic therapy, chronic use of non-steroidal anti-inflammatory drugs [NSAIDs]) Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of Effient.

If possible, manage bleeding without discontinuing Effient.

Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events [see Warnings and Precautions (5.3)].

patients with a history of TIA or ischemic stroke (>3 months prior to enrollment) had a higher rate of stroke on Effient (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage [ICH]) than on clopidogrel (1.2%; all thrombotic). In patients without such a history, the incidence of stroke was 0.9% (0.2% ICH) and 1.0% (0.3% ICH) with Effient and clopidogrel, respectively. Patients with a history of ischemic stroke within 3 months of screening and patients with a history of hemorrhagic stroke at any time were excluded from TRITONTIMI 38. Patients who experience a stroke or TIA while on Effient generally should have therapy discontinued [see Adverse Reactions (6.1) and Clinical Studies (14)].

4.3 Hypersensitivity: Effient is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS 5.1 General Risk of Bleeding: Thienopyridines, including Effient, increase the risk of bleeding. With the dosing regimens used in TRITONTIMI 38, TIMI (Thrombolysis in Myocardial Infarction) Major (clinically overt bleeding associated with a fall in hemoglobin ≥5 g/dL, or intracranial hemorrhage) and TIMI Minor (overt bleeding associated with a fall in hemoglobin of ≥3 g/dL but <5 g/dL) bleeding events were more common on Effient than on clopidogrel [see Adverse Reactions (6.1)].

The bleeding risk is highest initially, as shown in Figure 1 (events through 450 days; inset shows events through 7 days).

Figure 1: Non-CABG-Related TIMI Major or Minor Bleeding Events.

Non-CABG-Related TIMI Major or Minor Bleeding Events (%)

Effient® (prasugrel) tablets Brief Summary of Prescribing Information

Effient

5 4

Clopidogrel 3

3 2

2

patients) in the Effient group, compared with 5.0% (3 of 60 patients) in the clopidogrel group. For patients who received their last dose of thienopyridine within 4 to 7 days prior to CABG, the frequencies decreased to 11.3% (9 of 80 patients) in the prasugrel group and 3.4% (3 of 89 patients) in the clopidogrel group.

Do not start Effient in patients likely to undergo urgent CABG. CABGrelated bleeding may be treated with transfusion of blood products, including packed red blood cells and platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective.

5.3 Discontinuation of Effient: Discontinue thienopyridines, including Effient, for active bleeding, elective surgery, stroke, or TIA. The optimal duration of thienopyridine therapy is unknown. In patients who are managed with PCI and stent placement, premature discontinuation of any antiplatelet medication, including thienopyridines, conveys an increased risk of stent thrombosis, myocardial infarction, and death.

Patients who require premature discontinuation of a thienopyridine will be at increased risk for cardiac events. Lapses in therapy should be avoided, and if thienopyridines must be temporarily discontinued because of an adverse event(s), they should be restarted as soon as possible [see Contraindications (4.1 and 4.2) and Warnings and Precautions (5.1)].

5.4 Thrombotic Thrombocytopenic Purpura: Thrombotic thrombocytopenic purpura (TTP) has been reported with the use of Effient. TTP can occur after a brief exposure (< 2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment, including plasmapheresis (plasma exchange). TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragment red blood cells] seen on peripheral smear), neurological findings, renal dysfunction, and fever [see Adverse Reactions (6.2)].

5.5 Hypersensitivity Including Angioedema: Hypersensitivity including angioedema has been reported in patients receiving Effient, including patients with a history of hypersensitivity reaction to other thienopyridines [see Contraindications (4.3), Adverse Reactions (6.2)].

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience: The following serious adverse reactions are also discussed elsewhere in the labeling: • Bleeding [see Boxed Warning and Warnings and Precautions (5.1, 5.2)] • Thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.4)] Safety in patients with ACS undergoing PCI was evaluated in a clopidogrel-controlled study, TRITON-TIMI 38, in which 6741 patients were treated with Effient (60-mg loading dose and 10 mg once daily) for a median of 14.5 months (5802 patients were treated for over 6 months; 4136 patients were treated for more than 1 year). The population treated with Effient was 27 to 96 years of age, 25% female, and 92% Caucasian. All patients in the TRITON-TIMI 38 study were to receive aspirin. The dose of clopidogrel in this study was a 300-mg loading dose and 75 mg once daily.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials cannot be directly compared with the rates observed in other clinical trials of another drug and may not reflect the rates observed in practice.

Drug Discontinuation: The rate of study drug discontinuation because of adverse reactions was 7.2% for Effient and 6.3% for clopidogrel. Bleeding was the most common adverse reaction leading to study drug discontinuation for both drugs (2.5% for Effient and 1.4% for clopidogrel).

Bleeding: Bleeding Unrelated to CABG Surgery - In TRITON-TIMI 38, overall rates of TIMI Major or Minor bleeding adverse reactions unrelated to coronary artery bypass graft surgery (CABG) were significantly higher on Effient than on clopidogrel, as shown in Table 1.

Table 1: Non-CABG-Related Bleedinga (TRITON-TIMI 38)

PROOF

1 INDICATIONS AND USAGE 1.1 Acute Coronary Syndrome: Effient® is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: • Patients with unstable angina (UA) or non–ST-elevation myocardial infarction (NSTEMI).

• Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. Effient has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel. The difference between treatments was driven predominantly by MI, with no difference on strokes and little difference on CV death [see Clinical Studies (14)].

It is generally recommended that antiplatelet therapy be administered promptly in the management of ACS because many cardiovascular events occur within hours of initial presentation. In the clinical trial that established the efficacy of Effient, Effient and the control drug were not administered to UA/NSTEMI patients until coronary anatomy was established. For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial [see Warnings and Precautions (5.2)]. Because the large majority of patients are managed without CABG, however, treatment can be considered before determining coronary anatomy if need for CABG is considered unlikely. The advantages of earlier treatment with Effient must then be balanced against the increased rate of bleeding in patients who do need to undergo urgent CABG. 2 DOSAGE AND ADMINISTRATION Initiate Effient treatment as a single 60-mg oral loading dose and then continue at 10 mg orally once daily. Patients taking Effient should also take aspirin (75 mg to 325 mg) daily [see Drug Interactions (7) and Clinical Pharmacology (12.3)]. Effient may be administered with or without food [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

Dosing in Low Weight Patients: Compared to patients weighing ≥60 kg, patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients <60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied.

4 CONTRAINDICATIONS 4.1 Active Bleeding: Effient is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

4.2 Prior Transient Ischemic Attack or Stroke: Effient is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel),

1

1

0

0

0

Number at risk: Effient 6741 Clopidogrel 6716

90

6042 6023

0

1

2

3

4

5

6

7

180

270

360

450

5707 5764

4813 4883

4078 4138

2747 2792

Days from Randomization

Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures even if the patient does not have overt signs of bleeding.

Do not use Effient in patients with active bleeding, prior TIA or stroke [see Contraindications (4.1 and 4.2)].

Other risk factors for bleeding are: • Age ≥75 years. Because of the risk of bleeding (including fatal bleeding) and uncertain effectiveness in patients ≥75 years of age, use of Effient is generally not recommended in these patients, except in high-risk situations (patients with diabetes or history of myocardial infarction) where its effect appears to be greater and its use may be considered [see Adverse Reactions (6.1), Use in Specific Populations (8.5), Clinical Pharmacology (12.3), and Clinical Trials (14)].

• CABG or other surgical procedure [see Warnings and Precautions (5.2)].

• Body weight <60 kg. Consider a lower (5 mg) maintenance dose [see Dosage and Administration (2), Adverse Reactions (6.1), Use in Specific Populations (8.6)].

• Propensity to bleed (e.g., recent trauma, recent surgery, recent or recurrent gastrointestinal (GI) bleeding, active peptic ulcer disease, severe hepatic impairment, or moderate to severe renal impairment) [see Adverse Reactions (6.1) and Use in Specific Populations (8.7 and 8.8)].

• Medications that increase the risk of bleeding (e.g., oral anticoagulants, chronic use of non-steroidal anti-inflammatory drugs [NSAIDs], and fibrinolytic agents). Aspirin and heparin were commonly used in TRITON-TIMI 38 [see Drug Interactions (7), Clinical Studies (14)].

Thienopyridines inhibit platelet aggregation for the lifetime of the platelet (7-10 days), so withholding a dose will not be useful in managing a bleeding event or the risk of bleeding associated with an invasive procedure. Because the half-life of prasugrel’s active metabolite is short relative to the lifetime of the platelet, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective.

5.2 Coronary Artery Bypass Graft Surgery-Related Bleeding: The risk of bleeding is increased in patients receiving Effient who undergo CABG. If possible, Effient should be discontinued at least 7 days prior to CABG. Of the 437 patients who underwent CABG during TRITON-TIMI 38, the rates of CABG-related TIMI Major or Minor bleeding were 14.1% in the Effient group and 4.5% in the clopidogrel group [see Adverse Reactions (6.1)]. The higher risk for bleeding events in patients treated with Effient persisted up to 7 days from the most recent dose of study drug. For patients receiving a thienopyridine within 3 days prior to CABG, the frequencies of TIMI Major or Minor bleeding were 26.7% (12 of 45

Effient (%) Clopidogrel (%) (N=6741) (N=6716) TIMI Major or Minor bleeding 4.5 3.4 2.2 1.7 TIMI Major bleedingb Life-threatening 1.3 0.8 Fatal 0.3 0.1 Symptomatic intracranial 0.3 0.3 hemorrhage (ICH) Requiring inotropes 0.3 0.1 Requiring surgical 0.3 0.3 intervention Requiring transfusion 0.7 0.5 (≥4 units) 2.4 1.9 TIMI Minor bleedingb

p-value p=0.002 p=0.029 p=0.015

p=0.022

Patients may be counted in more than one row. b See 5.1 for definition.

Figure 1 demonstrates non-CABG related TIMI Major or Minor bleeding. a

The bleeding rate is highest initially, as shown in Figure 1 (inset: Days 0 to 7) [see Warnings and Precautions (5.1)].

Bleeding rates in patients with the risk factors of age ≥75 years and weight <60 kg are shown in Table 2.

Table 2: Bleeding Rates for Non-CABG-Related Bleeding by Weight and Age (TRITON-TIMI 38) Major/Minor Fatal Effient Clopidogrel Effient Clopidogrel (%) (%) (%) (%) Weight <60 kg (N=308 Effient, N=356 clopidogrel) Weight ≥60 kg (N=6373 Effient, N=6299 clopidogrel) Age <75 years (N=5850 Effient, N=5822 clopidogrel) Age ≥75 years (N=891 Effient, N=894 clopidogrel)

10.1

6.5

0.0

0.3

4.2

3.3

0.3

0.1

3.8

2.9

0.2

0.1

9.0

6.9

1.0

0.1

Bleeding Related to CABG - In TRITON-TIMI 38, 437 patients who received a thienopyridine underwent CABG during the course of the study. The rate of CABG-related TIMI Major or Minor bleeding was 14.1% for the Effient group and 4.5% in the clopidogrel group (Table 3). The higher risk for bleeding adverse reactions in patients treated with Effient persisted up to 7 days from the most recent dose of study drug.

Table 3: CABG-Related Bleedinga (TRITON-TIMI 38) TIMI Major or Minor bleeding TIMI Major bleeding Fatal Reoperation Transfusion of ≥5 units Intracranial hemorrhage TIMI Minor bleeding

Effient (%) Clopidogrel (%) (N=213) (N=224) 14.1 4.5 11.3 3.6 0.9 0 3.8 0.5 6.6 2.2 0 0 2.8 0.9

6.2 Postmarketing Experience: The following adverse reactions have been identified during post approval use of Effient. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders — Thrombocytopenia, Thrombotic thrombocytopenic purpura (TTP) [see Warnings and Precautions (5.4) and Patient Counseling Information (17.3)] Immune system disorders — Hypersensitivity reactions including anaphylaxis [see Contraindications (4.3)] 7 DRUG INTERACTIONS 7.1 Warfarin: Coadministration of Effient and warfarin increases the risk of bleeding [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

7.2 Non-Steroidal Anti-Inflammatory Drugs: Coadministration of Effient and NSAIDs (used chronically) may increase the risk of bleeding [see Warnings and Precautions (5.1)].

7.3 Other Concomitant Medications: Effient can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes [see Clinical Pharmacology (12.3)].

Effient can be administered with aspirin (75 mg to 325 mg per day), heparin, GPIIb/IIIa inhibitors, statins, digoxin, and drugs that elevate gastric pH, including proton pump inhibitors and H2 blockers [see Clinical Pharmacology (12.3)].

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy: Pregnancy Category B - There are no adequate and well-controlled studies of Effient use in pregnant women. Reproductive and developmental toxicology studies in rats and rabbits at doses of up to 30 times the recommended therapeutic exposures in humans (based on plasma exposures to the major circulating human metabolite) revealed no evidence of fetal harm; however, animal studies are not always predictive of a human response. Effient should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

In embryo fetal developmental toxicology studies, pregnant rats and rabbits received prasugrel at maternally toxic oral doses equivalent to more than 40 times the human exposure. A slight decrease in pup body weight was observed; but, there were no structural malformations in either species. In prenatal and postnatal rat studies, maternal treatment with prasugrel had no effect on the behavioral or reproductive development of the offspring at doses greater than 150 times the human exposure [see Nonclinical Toxicology (13.1)].

8.3 Nursing Mothers: It is not known whether Effient is excreted in human milk; however, metabolites of Effient were found in rat milk.

Because many drugs are excreted in human milk, prasugrel should be used during nursing only if the potential benefit to the mother justifies the potential risk to the nursing infant.

8.4 Pediatric Use: Safety and effectiveness in pediatric patients have not been established [see Clinical Pharmacology (12.3)].

8.5 Geriatric Use: In TRITON-TIMI 38, 38.5% of patients were ≥65 years of age and 13.2% were ≥75 years of age. The risk of bleeding increased with advancing age in both treatment groups, although the relative risk of bleeding (Effient compared with clopidogrel) was similar across age groups.

Patients ≥75 years of age who received Effient had an increased risk of fatal bleeding events (1.0%) compared to patients who received clopidogrel (0.1%). In patients ≥75 years of age, symptomatic intracranial hemorrhage occurred in 7 patients (0.8%) who received Effient and in 3 patients (0.3%) who received clopidogrel. Because of the risk of bleeding, and because effectiveness is uncertain in patients ≥75 years of age [see Clinical Studies (14)], use of Effient is generally not recommended in these patients, except in high-risk situations (diabetes and past history of myocardial infarction) where its effect appears to be greater and its use may be considered [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

8.6 Low Body Weight: In TRITON-TIMI 38, 4.6% of patients treated with Effient had body weight <60 kg. Individuals with body weight <60 kg had an increased risk of bleeding and an increased exposure to the active metabolite of prasugrel [see Dosage and Administration (2), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].

Consider lowering the maintenance dose to 5 mg in patients <60 kg.

The effectiveness and safety of the 5 mg dose have not been prospectively studied.

8.7 Renal Impairment: No dosage adjustment is necessary for patients with renal impairment. There is limited experience in patients with end-stage renal disease, but such patients are generally at higher risk of bleeding [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

8.8 Hepatic Impairment: No dosage adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B). The pharmacokinetics and pharmacodynamics of prasugrel in

patients with severe hepatic disease have not been studied, but such patients are generally at higher risk of bleeding [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

8.9 Metabolic Status: In healthy subjects, patients with stable atherosclerosis, and patients with ACS receiving prasugrel, there was no relevant effect of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel’s active metabolite or its inhibition of platelet aggregation.

10 OVERDOSAGE 10.1 Signs and Symptoms: Platelet inhibition by prasugrel is rapid and irreversible, lasting for the life of the platelet, and is unlikely to be increased in the event of an overdose. In rats, lethality was observed after administration of 2000 mg/kg. Symptoms of acute toxicity in dogs included emesis, increased serum alkaline phosphatase, and hepatocellular atrophy. Symptoms of acute toxicity in rats included mydriasis, irregular respiration, decreased locomotor activity, ptosis, staggering gait, and lacrimation.

10.2 Recommendations about Specific Treatment: Platelet transfusion may restore clotting ability. The prasugrel active metabolite is not likely to be removed by dialysis.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis - No compound-related tumors were observed in a 2-year rat study with prasugrel at oral doses up to 100 mg/kg/day (>100 times the recommended therapeutic exposures in humans (based on plasma exposures to the major circulating human metabolite). There was an increased incidence of tumors (hepatocellular adenomas) in mice exposed for 2 years to high doses (>250 times the human metabolite exposure).

Mutagenesis - Prasugrel was not genotoxic in two in vitro tests (Ames bacterial gene mutation test, clastogenicity assay in Chinese hamster fibroblasts) and in one in vivo test (micronucleus test by intraperitoneal route in mice).

Impairment of Fertility - Prasugrel had no effect on fertility of male and female rats at oral doses up to 300 mg/kg/day (80 times the human major metabolite exposure at daily dose of 10 mg prasugrel).

17 PATIENT COUNSELING INFORMATION See Medication Guide 17.1 Benefits and Risks • Summarize the effectiveness features and potential side effects of Effient.

• Tell patients to take Effient exactly as prescribed.

• Remind patients not to discontinue Effient without first discussing it with the physician who prescribed Effient.

• Recommend that patients read the Medication Guide.

17.2 Bleeding: Inform patients that they: • will bruise and bleed more easily.

• will take longer than usual to stop bleeding.

• should report any unanticipated, prolonged, or excessive bleeding, or blood in their stool or urine.

17.3 Other Signs and Symptoms Requiring Medical Attention • Inform patients that TTP is a rare but serious condition that has been reported with Effient.

• Instruct patients to get prompt medical attention if they experience any of the following symptoms that cannot otherwise be explained: fever, weakness, extreme skin paleness, purple skin patches, yellowing of the skin or eyes, or neurological changes.

• Inform patients that they may have hypersensitivity reactions including rash, angioedema, anaphylaxis, or other manifestations.

Patients who have had hypersensitivity reactions to other thienopyridines may have hypersensitivity reactions to Effient.

17.4 Invasive Procedures: Instruct patients to: • inform physicians and dentists that they are taking Effient before any invasive procedure is scheduled.

• tell the doctor performing the invasive procedure to talk to the prescribing health care professional before stopping Effient.

17.5 Concomitant Medications: Ask patients to list all prescription medications, over-the-counter medications, or dietary supplements they are taking or plan to take so the physician knows about other treatments that may affect bleeding risk (e.g., warfarin and NSAIDs).

Literature Revised: December 21, 2012 Effient® is a registered trademark of Eli Lilly and Company.

Manufactured by Eli Lilly and Company, Indianapolis, IN 46285 Marketed by Daiichi Sankyo, Inc. and Lilly USA, LLC Copyright © 2009, 2011, 2012 Daiichi Sankyo, Inc. and Eli Lilly and Company. All rights reserved.

PG82128. PGHCPBS03Dec2012.

PV 7802 AMP PRINTED IN USA

PROOF a Patients may be counted in more than one row.

Bleeding Reported as Adverse Reactions - Hemorrhagic events reported as adverse reactions in TRITON-TIMI 38 were, for Effient and clopidogrel, respectively: epistaxis (6.2%, 3.3%), gastrointestinal hemorrhage (1.5%, 1.0%), hemoptysis (0.6%, 0.5%), subcutaneous hematoma (0.5%, 0.2%), post-procedural hemorrhage (0.5%, 0.2%), retroperitoneal hemorrhage (0.3%, 0.2%), pericardial effusion/hemorrhage/tamponade (0.3%, 0.2%), and retinal hemorrhage (0.0%, 0.1%).

Malignancies: During TRITON-TIMI 38, newly diagnosed malignancies were reported in 1.6% and 1.2% of patients treated with prasugrel and clopidogrel, respectively. The sites contributing to the differences were primarily colon and lung. It is unclear if these observations are causallyrelated or are random occurrences.

Other Adverse Events: In TRITON-TIMI 38, common and other important non-hemorrhagic adverse events were, for Effient and clopidogrel, respectively: severe thrombocytopenia (0.06%, 0.04%), anemia (2.2%, 2.0%), abnormal hepatic function (0.22%, 0.27%), allergic reactions (0.36%, 0.36%), and angioedema (0.06%, 0.04%). Table 4 summarizes the adverse events reported by at least 2.5% of patients.

Table 4: Non-Hemorrhagic Treatment Emergent Adverse Events Reported by at Least 2.5% of Patients in Either Group

Effient (%) Clopidogrel (%) (N=6741) (N=6716) Hypertension 7.5 7.1 Hypercholesterolemia/Hyperlipidemia 7.0 7.4 Headache 5.5 5.3 Back pain 5.0 4.5 Dyspnea 4.9 4.5 Nausea 4.6 4.3 Dizziness 4.1 4.6 Cough 3.9 4.1 Hypotension 3.9 3.8 Fatigue 3.7 4.8 Non-cardiac chest pain 3.1 3.5 Atrial fibrillation 2.9 3.1 Bradycardia 2.9 2.4 9 2.8 3.5 Leukopenia (<4 x 10 WBC/L) Rash 2.8 2.4 Pyrexia 2.7 2.2 Peripheral edema 2.7 3.0 Pain in extremity 2.6 2.6 Diarrhea 2.3 2.6

[

]

I WEAR IT BECAUSE...

PROOF

my grandson just taught me how to be a kid again.

Prescribe it to protect him from sudden cardiac arrest.

He will wear it for so many other reasons.

LifeVest median daily use is 94% or 22.6 hours per day

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800.543.3267 | www.zoll.com ©2012 ZOLL Medical Corporation. All rights reserved. ZOLL and LifeVest are trademarks and/or registered trademarks of ZOLL Medical Corporation in the United States and/or other countries.

ZOLL. Patient Use, Indications, and Coverage. February 2012. Available at http://www.lifevest.zoll.com/medical-professionals/patientuse.asp, Accessed February 28, 2012.

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Whiting J, Simon M. Health and Lifestyle Benefits Resulting from Wearable Cardioverter Defibrillator Use. The Journal of Innovations in Cardiac Rhythm Management, March 2012: 1-2.

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Saving Hearts in Need, One Pacemaker at a Time.

ving Quality of Life Patient

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The Physician and artbeat International Foundation Philanthropy

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By Dr. Benedict S. Maniscalco countries.

Old, young, and everyone in

including 1,000 pacemake 2,000 pacemaker and ICD

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Martina, happy and healthy after her implant procedure

waiting for weeks, perhaps months, for help that might have never come, Martina was quickly fitted with a pacemaker donated by Berlin-based cardiac device manufacturer BIOTRONIK, and now has many years of life ahead of her.

One to three million people in the world die every year because they cannot Newafford CCIa pacemaker or an implantable cardiovertor defibrillator (ICD). In Trinidad Practitioner Exam and Tobago alone, as many as 150 people at a time havewww.HeartbeatSavesLives.org been on the waiting list for a cardiac device,SESSIONS SUPPLEMENT 2014 HRS SCIENTIFIC underscoring just how great a need exists in this small

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BIOTRONIK is now enterin worldwide leader in develo Even as early as 1963, wh Schaldach and Otto Frank pacemaker, its objective w Jeremiah’s Hope technologies to sa Benefitsmedical Cambodia of life. At its core, this mis “excellence for life” should egalitarian as possible. But one thing to innovate new in expert medical care, bu that that care actually gets need it most.

To that end, BIOTRONIK s HBI in 2010. The choice w foundation also has a sim Saving Lives mission at its core: to insu in Indiaworld would die due to his to afford a lifesaving cardi ONE HEART MAGAZINE 7 implant centers and work as far-flung as India, Pakis

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One Heart.

One World.

ONE HEART MAGAZINE HRS Scientific Sessions Supplement • May 7-10, 2014

ONE HEART MAGAZINE HRS Scientific Sessions Supplement • May 7-10, 2014

Corporate Headquarters 4302 Henderson Blvd., Ste 102 Tampa, Florida 33629, USA Tel. (813) 259-1213

Publisher Adam Longaker The Custom Publishing Company

PROOF Chairman Heartbeat International Foundation Dr. Benedict S. Maniscalco

Executive Vice President Heartbeat International Foundation Laura Maniscalco DeLise Vice President of Business Development Johnathan Hartmand Accounting Leanne Ragano Charles Stevens Advertising Associates Jason Easton Penn Mills Gage Pierce

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Creative Director Bryan Clapper Editorial Director Kevin Anderson Sales Support Staff Michelle Santiago Alfredo Escandion Contributing Writers Dr. Paul Levine Dr. Benedict Maniscalco Dr. Harry Mond Dr. Federico Alfaro

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Heartbeat International Support Staff Georgina Cronin Christine Conley Michael Maniscalco Production Associate Michael Johns Legal Counsel Albert Salem, Esquire Special Thanks Heart Rhythm Society St. Jude Biotronik Heartbeat International Foundation American College of Cardiology

©Copyright 2014 Heartbeat International Foundation. All rights reserved. Reproduction of editorial content in whole or in part without written permission is prohibited.

Heartbeat International Foundation does not assume responsibility for the advertisements, nor any representation made therein, nor the quality or deliverability of the products themselves.

Reproduction of articles and photographs, in whole or in part, contained herein is prohibited without expressed written consent of the publisher, with the exception of reprinting for news media use. Printed in the United States of America.

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THEIR LEGACIES I LIVE ON Welcome to the Heart Rhythm Society 2014!

ntro letter

The field of electro

Sincerely,

Benedict S. Maniscalco, M.D. Chairman, C.E.O. Heartbeat International Foundation, Inc.

ABOUT DR. BENEDICT S. MANISCALCO Dr. Benedict S. Maniscalco, chairman and CEO of Heartbeat International, has been a private practitioner specializing in cardiovascular diseases since 1976.

In addition to his work in preventive and consultative cardiology, he serves as medical advisor to multiple companies involved in medically related business. Well regarded as an innovator and educator in cardiovascular medicine, Dr. Maniscalco has been engaged with the American College of Cardiology at the local, state, and national levels, serving in leadership roles that have directly influenced healthcare practices and policy.

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After graduating from the Duke University School of Medicine, Dr. Maniscalco interned at Grady Memorial Hospital in Atlanta and did his junior and senior residencies at Emory University and its affiliated hospitals, and followed that with a fellowship in cardiovascular diseases from 1973â&#x20AC;&#x201C;1975.

He served on the faculty at the University of South Florida School of Medicine before leaving to found the St. Josephâ&#x20AC;&#x2122;s Heart Institution in Tampa, Florida. He is a member of the American Medical Association, American Heart Association and a Fellow of the American Heart Association, the American College of Cardiology, the American College of Physicians, the American College of Chest Physicians, and the Society for Cardiac Angioplasty.

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The

PHYSICIAN andPHILANTHROPY A LIFE OF SERVICE

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Presented by Benedict S. Maiscalco, M.D. F.A.C.C. Chairman & CEO – Heartbeat International Foundation, Inc.

A

s children, adults often asked us what we want to be when we grow up.

Almost invariably, any child who said they want to be a doctor would explain their reason in these simple terms: “To help people, of course!” This urge to uplift humankind is a universal experience; it is universally repeated in every culture around this globe. I’ve had the great privilege of visiting many of the operating units of Heartbeat International, a charitable organization headquartered in Tampa, Florida, and this commonality has been validated to me time and time again during my travels.

The profession of physician is a noble one, and through my work with Heartbeat International, I have come to understand that the hallmarks of this profession truly are service and philanthropy. This may seem surprising, since most people consider philanthropists to be very wealthy people who give large sums of money from their great wealth. The word philanthropist itself invokes names like Bill and Melinda Gates, Warren Buffet, the Ford Foundation, or the Rockefeller Foundation. While these individuals and foundations represent certain aspects of philanthropy, I think of philanthropists more broadly, and my views have been shaped by my experiences www.HeartbeatSavesLives.org

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with Heartbeat International. I will define my terms in such a way as to illustrate how each physician is, in fact, a philanthropist.

To make my case, I emphasize four words that represent roles that all doctors play: student, teacher, professional, and lastly, but perhaps most vitally, philanthropist. Each of these roles is crucially important, and all doctors must balance them with the other hats that they wear: spouse, parent, colleague. Whatever other roles a doctor assumes, these four in particular— student, teacher, professional, and philanthropist— follow them every day of their life in the practice of medicine.

Doctors all inherently begin as students, entering medical school as learners formally enrolled in an institution. This depicts a rather narrow view of a student, however; in fact, a student is much more.

The word “student” is derived from the Latin studere, meaning, “one who directs one’s zeal at.” Zeal does not just indicate an interest in a topic; it implies great enthusiasm, passion, and joy in pursuing something.

I think of a student as one who directs their passion towards a subject, or simply, as one who is learning.

Every human being is learning every single day, in one capacity or another, but medical students learn a particular area, and it is my sincere hope that each and every medical student has the joy, zeal, and passion for that learning—since they will continue to be a student the rest of their life as a doctor.

The word “doctor” comes from the Greek docere, and it means, “to teach.” A doctor, therefore, is a teacher.

To be a worthy teacher, one must be an excellent observer and an excellent communicator. A doctor, and therefore teacher, must give of themselves to their students—students who are of many different varieties, including patients, medical students, colleagues, and family members.

In order to be a successful teacher and doctor, one must not only be an excellent communicator; above all, a doctor must be an advocate for their patients, for if they ever give up advocating for their patients, they will have struck the death knell for the practice of medicine.

The sacred relationship between patient and doctor is what makes medicine such a noble profession.

Doctors are not only students and teachers, they are also members of a profession that requires constant learning. I have developed a simple method for learning that I recommend to all members of the medical profession. I think of it as my “Four A’s”: acquire, attach, apply, and accumulate. The first “A” refers to acquiring facts and data, and learning to classify and reclassify that data. The second “A” refers to attaching the acquired data to other facts or sets of facts and data, which results in information. The third “A” occurs when one applies that information and creates knowledge, which is particular and singular to each individual doctor based on the

information they’ve acquired and synthesized. The fourth and final “A” takes place when one continues to accumulate knowledge, and that accumulated knowledge eventually represents some portion of wisdom. In the life of a physician, the practice of these “Four A’s”—acquire, attach, apply, and accumulate—is constant and occurs every single day; it is the very heart of medicine.

Describing professionals of any field, Judge Albert Tuttle said the following meaningful words: “The professional man [or woman] is, in essence, one who provides service. Do not try to set a price on yourselves, but do not be a miser, hoarding your talents and your abilities and your knowledge, either amongst yourselves or in your dealings with your clients, patients, or flock. Rather, be reckless and spendthrift, pouring out your talent to all to whom it can be of service. Throw it away, waste it; and in the spending, it can be of great service. Like love, talent is useful only in its expenditure, and it is never exhausted. Certain it is that man must eat, so set what price you must on your service. But never confuse the performance, which is great, with the compensation—be it money, power, or fame—which is trivial.”

True professionals—doctors included—provide services, instruction, education, and the sharing of knowledge without regard for compensation. It is done out of compassion, which leads me to the word “philanthropy,” derived from the Greek word “to love.”

In my estimation, a key attribute of all philanthropists is that they treasure the voluntary promotion of the welfare of humankind. Philanthropists give their time, talent, or treasury to a socially worthy cause without expectation of personal, financial, or material reward. Philanthropists practice beneficence—the generous support of the poor.

Members of the medical profession must have within themselves the spirit of philanthropy and enter into the profession for the right reason: service. When the profession is practiced with service as the guiding principle, the rewards are, in fact, enormous and come from unexpected sources. Philanthropy and the voluntary promotion of human wellbeing is a reward, in and of itself.

From my own life, there is one particular story that consummately demonstrates the application of these principles. It is the story of a student and a professor—Dr. Federico Alfaro and Dr. Henry McIntosh—and it began with a simple event that changed a bit of the world.

Federico Alfaro was a trainee in cardiology at Baylor University under Dr. McIntosh. One day, as they were making rounds, Dr. McIntosh was presented with a patient that needed a pacemaker. Dr. McIntosh explained that the patient would have one by that afternoon.

The young Federico was visibly shaken, and so Dr. McIntosh asked how he had offended him. Federico replied that in Guatemala, before he came to Baylor University, he had watched a young 17-year-old boy die

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because they could not give him the pacemaker he so desperately needed; there was no money for it and no agency to provide it. Federico shared that in light of the ease with which Dr. McIntosh’s patient would receive a pacemaker within a day, he could not help but remember that this would not be possible in Guatemala.

Several years later, in 1983, Dr. Alfaro was in Guatemala City. He had become a member of the Rotary Club, and Dr. McIntosh came to visit his former student.

Dr. McIntosh learned of Dr. Alfaro’s initiative to provide pacemakers to needy patients. Dr. Alfaro had become a man of service in the Rotary Club, and he was exhibiting philanthropy and beneficence through his concern for humankind. This was a sterling example of a student teaching his professor about a potential mechanism to administer assistance to those in need.

When Dr. McIntosh learned about Dr. Alfaro’s initiative, he resolved to immediately address the problem upon his return to the United States. Dr. McIntosh obtained 400 pacemakers and acquired leads from contacts and collaborators from Rotary International. All within a year, with Dr. Alfaro leading the charge, they brought together doctors from Central America, Mexico, and South America to form Heartbeat International.

By 1986, Heartbeat International was in 18 countries.

The organization received a presidential citation by President Ronald Regan as an exemplary model of private-public activities for the welfare of man, and it was sponsored at two different times by the Watson Clinic in Lakeland and by St. Joseph’s Hospital in Tampa, Florida. This extraordinary global charitable organization came into existence all because of a project in Guatemala initiated by one man in order to address a concern for the wellbeing of humankind.

I had the great privilege to study under Dr. McIntosh at Duke University. When he was retiring from the Watson Clinic, he expressed to me that he was not concerned about his retirement; he was concerned only for Heartbeat International. Having never heard of it before, I asked him, “What is Heartbeat International?” When he told me about the organization and all it had achieved, I marveled at the fact that my former professor—a man who brilliantly instructed me in clinical medicine and cardiology—was now a world-class philanthropist, as well.

In 1994, we brought Heartbeat International to St. Joseph’s Hospital in Tampa, where I was the head of the Heart Institute, and in 2002 I accepted Dr. McIntosh’s challenge to lead Heartbeat International into the future. That year, in 2002, Heartbeat International was in 22 countries. Today, we’re in Central America, South America, Africa, Europe, Asia, the Caribbean, and the Pacific—and the future is unlimited. Through an idea born in Guatemala City thirty years ago, we have now facilitated countless individuals to render philanthropic efforts on behalf of humankind in numerous cities

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and countries around the world. The professionals at Heartbeat International are shining examples of doctors who are performing their role to the fullest—as students, teachers, professionals, and philanthropists.

Although Dr. Henry McIntosh died in 2008, he remains, to those of us who knew him, a guiding beacon of light in the world of medicine and humanity. He is a paragon of genuine concern for humankind. He and Dr. Alfaro continue to be an inspiration to all of us at Heartbeat International. Based on their stirring example, the guiding philosophy of Heartbeat International has always been, “We give pacemakers as peacemakers, and the service that we give to our fellow man is the rent we pay to live on this earth.”

And so, for any member of the medical profession, new or experienced, and especially for anyone considering the path of medicine, I encourage you to value and enact

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PROOF these four rolesâ&#x20AC;&#x201D;student, teacher, professional, and philanthropist. Wear each of these hats with pride, and wear them every day, ever cognizant that you deal with a unique and singular product: human life and the welfare of humankind.

Above all, to achieve authentic success in the medical profession, remember to embody the principles of the philanthropist. This means that if you want to be the best, become compassionate, caring, and concerned. Be humble, kind, and generous of spirit. Donâ&#x20AC;&#x2122;t be afraid to give of yourself to your patients so they know you are human, just as they are. Treat each of your patients like a member of your family, and you will enjoy the incredible thrill of receiving their love, affection, and respect for you in return. Have personal knowledge of your patients, because you cannot treat a patient effectively if you only treat the disease. You must know your patients, and www.HeartbeatSavesLives.org

individualize your application of knowledge in a personal and humane manner. Let your treatment be more than a transaction; let it be a service to each and every patient.

The essence of service is the essence of medicine, and it is most clearly manifested through the doctor-patient relationship.

I believe physicians are the greatest philanthropists on Earth, for they give of themselves every day, all for the love of performing service to humankind. They continually learn and teach while sharing their joys, talent, and knowledge. In my years in the field of medicine, I have experienced the gratification of giving and I have received back far more than I ever gave. The life of medicine is the life of service, and the best doctors are, in truth, the very best philanthropists.

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Martina Riddess, first wrote to HBI with a plea to help her mother. Martina was already suffering from heart disease and knew she couldn’t afford a pacemaker. In Nadine’s heartfelt and moving letter to the Heartbeat International Foundation (HBI), she detailed a life of struggle after the sudden death of her father in 2003: “My mother has no type of pension, but a senior’s benefit that is only enough for day-to-day spending.

I had to become the breadwinner of the family, and sometimes, we stillbetween live only paycheck to paycheck.”

Partnership BIOTRONIK and

Saving Lives and Improving Quality of Life Can Start with Just One Patient

Heartbeat International Foundation As Martina any medical she bringsdid aidnottohave many of the insurance, world’s poorest countries. was entirely dependent on her daughter. Nadine, as much as she wished to, knew that she could not afford a pacemaker and Joy medical carethe for adult her mother, noof When Nadine Villaroel, daughter matter how long and hard she worked.

When Martina Martina Riddess, first wrote to HBI with a plea to help ended in theMartina emergency at suffering the Mount Hope her up mother. was room already from heart Hospital, Nadine knewshe shecouldn’t need toafford createa some hope In disease and knew pacemaker. of her own. After fourand days, duringletter which Nadine’s heartfelt moving to her the mother Heartbeat wasInternational on a temporary pacemaker but in desperate need Foundation (HBI), she detailed a life of of astruggle permanent one, Nadine gathered up her courage after the sudden death of her father in 2003: and“My wrote, “I amhas requesting fullpension, assistance HBI. mother no type of butfrom a senior’s Please accept letterenough as it isfor myday-to-day truthful plea for benefi t thatthis is only spending. urgent help.”

I had to become the breadwinner of the family, and sometimes, still live only paycheck to paycheck.”

Luckily, HBI hadwe already established a national heart

Martina, happy and healthy after her implant procedure

waiting for weeks, perhaps months, for help that might have never come, Martina was quickly fitted with a pacemaker donated by Berlin-based cardiac device manufacturer BIOTRONIK, and now has many years of life ahead of her.

One to three million people in the world die every year because they cannot afford a pacemaker or an implantable cardiovertor defibrillator (ICD). In Trinidad and Tobago alone, as many as 150 people at a time have been on the waiting list for a cardiac device, underscoring just how great a need exists in this small center at Mountdid Hope St. any Augustine, Trinidad and she island nation. While the government healthcare system As Martina not in have medical insurance, there pays for many medical it does not Tobago, and Nadine’s urgentoncall help reached Martina, happy and healthy expenses, after her implant procedure was entirely dependent herfordaughter.

Nadine, as cover the cost of these cardiac devices.

The cost of the the much volunteer doctors at the center in time.

Instead of as she wished to, knew that she could not afford pacemaker itself as well as the months, costs of implantation can waiting for weeks, perhaps for help that might a pacemaker and medical care for her mother, no US$3,000 to $8,000, while implanting have never come, Martina wassuccesfully quickly fitted with a matter how long and hard she worked. When Martina reach can even cost as by much as US$20,000 – adevice great pacemaker donated Berlin-based cardiac ended up in the emergency room at the Mount Hope an ICD deal more than the per capita income of Trinidad manufacturer BIOTRONIK, and now has manyand years Hospital, Nadine knew she need to create some hope 1 percent of the population lives below Tobago of life, where ahead 17 of her. of her own. After four days, during which her mother 2 was on a temporary pacemaker but in desperate need the poverty line . The situation is dire, and without One to three million people in the world die every of a permanent one, Nadine gathered up her courage outside help from charities such as HBI, many people year because they cannot afford a pacemaker or an and wrote, “I am requesting full assistance from HBI. who need a pacemaker or ICD may live a seriously implantable cardiovertor defibrillator (ICD). In Trinidad compromised life or even die.

Please accept this letter as it is my truthful plea for and Tobago alone, as many as 150 people at a time urgent help.”

But have Martina and patients are given a been onother the waiting listlike forher a cardiac device, chance atjust life how with great devices that may small, underscoring a need existsseem in this small Luckily, HBI had already established a national heart second but actually have a much bigger impact than many island nation. While the government healthcare system center at Mount Hope in St. Augustine, Trinidad and canthere imagine. the nearly four years since BIOTRONIK paysInfor many medical expenses, it does not Tobago, and Nadine’s urgent call for help reached HBI have begun their partnership, BIOTRONIK the cost of these cardiac devices.

The costhas of the the volunteer doctors at the center in time. Instead of andcover A BIOTRONIK-donated pacemaker saved Martina’s life donated roughly 1,000 life-saving year, pacemaker itself as well as the devices costs ofper implantation can reach US$3,000 to $8,000, while succesfully implanting an ICD can even cost as much as US$20,000 – a great deal more than the per capita income of Trinidad and Tobago 1, where 17 percent of the population lives below the poverty line 2. The situation is dire, and without outside help from charities such as HBI, many people who need a pacemaker or ICD may live a seriously compromised life or even die.

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A BIOTRONIK-donated pacemaker saved Martina’s life

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But Martina and other patients like her are given a second chance at life with devices that may seem small, but actually have a much bigger impact than many can imagine. In the nearly four years since BIOTRONIK and HBI have begun their partnership, BIOTRONIK has donated roughly 1,000 life-saving devices per year,

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including 1,000 pacemakers, nearly 500 ICDs and over 2,000 pacemaker and ICD leads.

everyone in between. HBI sponsors the opening of heart centers in these developing countries, which then recruit such people to form a base of volunteers who will always be there when the need arises.

BIOTRONIK is now entering its sixth decade as a worldwide leader in developing life-saving devices.

HBI’s Pacemaker Program has only two requirements: Even as early as 1963, when its two founders Max medical need and economic need. All potential patients Schaldach and Otto Franke invented the first German must be assessed in their home country by an HBI pacemaker, its objective was already clear: innovating certified volunteer doctor and must meet the indigent medical technologies to save lives and increase quality status outlined by local social workers. Once the patient of life. At its core, this mission, defined by the motto is deemed eligible, a BIOTRONIK-donated device is “excellence for life” should be as undiscerning and egalitarian as possible. But therein lies the problem: it’s implanted and the heart center provides life-long follow-up care. This guarantees that some of the world’s one thing to innovate new solutions to aid physicians in expert medical care, but it is quite another to ensure Old, young, and everyone in between: HBI helps heart patients ofpoorest all agespatients will receive the treatment they need that that care actually gets to patients like Martina who to go back to living their lives and, very often, return to waiting families. need it most. everyone in between. HBI sponsors the opening of including 1,000 pacemakers, nearly 500 ICDs and over heart centers in these developing countries, which then 2,000 pacemaker and ICD leads.

At its core, it is a miracle that heart conditions such as To that end, BIOTRONIK signed a partnership with recruit such people to form a base of volunteers who the one Martina suffered from can be cured by medical HBI in 2010.isThe choice wasits clear, the non-profi BIOTRONIK now entering sixthasdecade as a t will always be there when the need arises. technology; that humanity has come far enough to foundation leader also has similarly excellent worldwide in adeveloping life-savinglife-saving devices. connect the physical with the to keep the mission at its as core: to insure no founders patient inMax the HBI’s Pacemaker Program hasmechanical only two requirements: Even as early 1963, when that its two heart beating on end.

For All Nadine, writing that world would dieOtto dueFranke to his or her notthe being medical need for andyears economic need. potential patients Schaldach and invented firstable German letter wasassessed an act ofingreat an acknowledgment to afford a lifesaving cardiac implant.clear: Establishing must be theircourage: home country by an HBI pacemaker, its objective was already innovating that her mother Martina’s lifemeet would implant centers and working with and doctors in countries certifisaving ed volunteer doctor and must thetake indigent medical technologies to save lives increase quality something of a by miracle as well.

In fact, Once it would as life. far-flAt ung India, Mexico, status outlined local social workers. thealso patient of itsas core, thisPakistan, mission, Guatemala, defined by the motto take a dedication – and a vision of is Ecuador, Venezuela and thebe Philippines, HBI finds is deemed eligible,toaexcellence BIOTRONIK-donated device “excellence for life” should as undiscerning and for the life”heart that still stands at thelife-long heart of what helping hands on the ground – doctors, nurses, implanted and center provides egalitarian as possible.

But therein lies the problem: it’s “excellence BIOTRONIK andThis HBIguarantees do together, and as a of goal their and thing hospitals – to diagnose and treattovulnerable follow-up care. that some thefor world’s one to innovate new solutions aid physicians ongoing successful heart patients, from new-born to seniors and poorest patients willpartnership. receive the treatment they need in expert medical care, but it isbabies quite another to ensure that that care actually gets to patients like Martina who to go back to living their lives and, very often, return to waiting families. need it most.

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To that end, BIOTRONIK signed a partnership with HBI in 2010. The choice was clear, as the non-profit foundation also has a similarly excellent life-saving mission at its core: to insure that no patient in the world would die due to his or her not being able to afford a lifesaving cardiac implant. Establishing implant centers and working with doctors in countries as far-flung as India, Pakistan, Guatemala, Mexico, Ecuador, Venezuela and the Philippines, HBI finds helping hands on the ground – doctors, nurses, and hospitals – to diagnose and treat vulnerable heart patients, from new-born babies to seniors and

At its core, it is a miracle that heart conditions such as the one Martina suffered from can be cured by medical technology; that humanity has come far enough to connect the physical with the mechanical to keep the www.HeartbeatSavesLives.org heart beating for years on end. For Nadine, writing that letter was an act of great courage: an acknowledgment that saving her mother Martina’s life would take something of a miracle as well. In fact, it would also take a dedication to excellence – and a vision of “excellence for life” that still stands at the heart of what BIOTRONIK and HBI do together, and as a goal for their ongoing successful partnership.

One Heart. One World.

1 http://www.state.gov/r/pa/ei/bgn/35638.htm, 2 https://www.cia.gov/library/publications/the-world-factbook/geos/td.html

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1 http://www.state.gov/r/pa/ei/bgn/35638.htm, 2 https://www.cia.gov/library/publications/the-world-factbook/geos/td.html

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JEREMIAH’S HOPE:

BRINGING QUALITY CARE

TO CAMBODIA

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By Sarah H. Choe

O

n April 17, 1975, Pol Pot and the Khmer Rouge took over Cambodia. Their goal: create a utopian socialist society where everyone was equal as a rice farmer. To reach this goal, the Khmer Rouge murdered all scholars, military officers, professionals, and political, civic, and religious leaders. This marked the beginning of a reign of terror or the “killing fields” in the former French colony. Among those executed to create this perfect society were the physicians. In 1975, there were around 950 people trained in the profession. After the executions, only 38 remained; after Khmer Rouge lost power and peace was restored in 1979, only 20 were left.

Although it was only four years, those years of neglect caused significant damage to Cambodia’s health care system.

Cambodia is now a country of approximately 14 million. Of this number, 20% live below the poverty line, surviving on less than one dollar per day. Even an average Cambodian only makes around $880 a year. The majority live in the countryside and farm. Life expectancy is low and access to health care depends on where a person lives.

In 2000, Dr. Dan Smith, Dr. Mark Sheehan, and Reverend Setan Lee founded the organization Christian Medical Ministry to Cambodia/Jeremiah’s Hope or CMMCJH (cmmcjh.com). Their vision: offer excellent medical care to the poor and quality medical education to the healthcare community of Cambodia. What started with a vision has grown in the past 14 years. CMMCJH’s clinic, located in the heart of downtown Phnom Penh near the Sianoukville Hospital, now employs 3 full time physicians and 17 nurses and administrators which operate year round. This clinic has two fully functional operating suites along with 19 post-op beds. Throughout each year, teams from Denver, Colorado go to support the clinic by assisting and training the Cambodian staff and physicians. These teams include general surgery, orthopedics, ENT, neurosurgical, and cardiac surgery. In 2013 alone, over 200 surgical procedures were performed ranging from minor surgeries to complex ones.

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The cardiac team’s annual mission is in February. We work in our clinic, evaluating patients who are referred to us by missionaries and physicians throughout the year.

We perform echocardiograms to decide if cardiac surgery is indicated. To date, over 120 complex cardiac surgeries for rheumatic valvular disease, congential heart disease

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have been performed. Since 2007, we have been working closely at the Calmette Hospital Heart Center, Cambodia’s only heart hospital. The Heart Center has two operating theaters and one cardiac catheterization laboratory. In addition to helping patients, our mission is to help train the Cambodian medical students and physicians. Medical students work with us as interpreters and learn physical exam skills. We work with the residents and physicians at the Calmette Hospital Heart Center teaching and learning from them as well. We work closely with the physicians and have assisted in successfully training two electrophysiologists who are now capable of implanting devices of their own.

Jeremiah’s Hope has brought over donated equipment to set up a fully functional electrophysiology laboratory (the only one in Cambodia) which has been performing catheter ablations since its beginning four years ago.

Jeremiah’s Hope has been able to implant pacemakers, averaging around 5 pacemakers a year, all donated by the manufacturers. This all varies on the number of donations. In the past four years, we have implanted one ICD. We have been fortunate in getting donated products from the major manufacturers, but in limited quantity.

We raise funds throughout the year in order to care for the patients who cannot afford medical care themselves. $500 will pay to implant a pacemaker (not including the 26

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donated device). $3500 will pay for one patient to get complex cardiac surgery.

Jeremiah’s Hope has always relied on the annual pacemaker donations made by manufacturers. However, over the past few years these donations have become more difficult to obtain. This is why we are so excited to announce our partnership with Heartbeat International.

With the supply of devices covered, we hope to increase the number of patients we are able to treat each year.

Patients in desperate of surgery will no longer need to wait until we arrive each year to have a pacemaker implanted.

Jeremiah’s Hope has been able to touch and save the lives of many. We have been able to meet incredible people and not only help others, but also provide the tools so that Cambodian doctors may also help their country after we have left. The Khmer Rouge left the healthcare system in Cambodia in shambles, all in a matter of years. Cambodia has made significant progress since then and is continuing to move forward. However there is a large indigent population which will benefit from the partnership of Jeremiah’s Hope and Heartbeat International which shares similar goals of education, prevention and treatment. We are proud to be a member of the Global Cardiovascular Alliance and together we hope to help save the lives of many.

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CCI ANNOUNCES NEW INTERNATIONAL ECHO PRACTITIONER EXAM

By Stephanie Ricker

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ardiovascular Credentialing International (CCI) is pleased to announce its new International Echo Practitioner (IEP) exam as part of a collaborative effort to improve cardiac ultrasound worldwide.

The need for sonography in developing countries is extreme; healthcare providers are facing serious challenges. Rheumatic heart disease is the biggest threat. “These countries have a much higher incidence rate of rheumatic heart disease than we do here in the States, and it’s a disease of the young,” says David Adams, RCS, RDCS, FASE, Cardiac Sonographer at Duke University Medical Center and member of CCI’s Board of Advisors. The second biggest challenge consists of non-communicable diseases like hypertension, diabetes, and coronary disease. Adams continues, “We need to give nurses, sonographers, and physicians the tools to perform a quick screening for these diseases.”

Patients ignoring symptoms is one obstacle to care in developing countries, but the main issue is the severe shortage of trained sonographers. “Many people do not seek out medical attention because they can’t afford it. But when they do seek it out, they often travel thousands of miles and wait months to be seen,” says Richie Palma, RCS, RDCS, FASE, Director and Clinical Coordinator of the Cardiac Ultrasound School at St. Francis Hospital and Medical Center, Chair of CCI’s IEP Examination Task Force, and member of CCI’s Board of Advisors. The problem is lack of education, not lack of equipment: ultrasound machines, while often older donated models, are seriously underutilized 28

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due to the limited education available for using them. “In Rwanda, for example, there are only five cardiologists in a country of ten million people,” says Adams. “They need more people performing echoes.” Palma agrees: “An ASE [American Society of Echocardiography] team went to India two years ago with a crew of sonographers who performed 900 echoes in one day, setting a world record. However, literally thousands of people were waiting outside the tents and had to be turned away at the end of the day. We just barely scratched the surface.”

The use of ultrasound in developing countries is very

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different than it is in the US or Europe. Many countries don’t have an ultrasound profession: ultrasounds are performed only by physicians and are used in clinics to make immediate patient management decisions. The people performing these scans have basic echo skills, but they don’t yet possess the advanced skills that would allow them to sit and pass the sonographer exam or physician exam.

Recognizing this scarcity of education, an international group approached the American Society of Echocardiography (ASE), told them about the lack of training and personnel, and asked for ASE’s assistance. David Adams says, “These people have a thirst for education. When we travel, that’s the question we get the most: How can we learn this?” In response, ASE created the International Sonographer Task Force to develop free modules to train people across the

2nd World Summit on Echocardiography in New Delhi, India, in the fall of 2013, and the exam is scheduled to launch in summer of 2014.

CCI, a not-for-profit credentialing body, has administered cardiovascular credentialing examinations for 45 years and currently provides certification to over 20,000 cardiovascular professionals globally. All credentialing programs administered by CCI have gained ISO/IEC 17024 accreditation by the American National Standards Institute (ANSI), the United States representative of the International Organization of Standardization (ISO). Currently, CCI administers two certificate-level and six registry-level credentialing examinations, including the Registered Cardiac Sonographer (RCS) and the Registered Congenital Cardiac Sonographer (RCCS).

Palma hopes that the addition of the IEP exam will further professional growth in developing countries: “An exam covering these basic skills will serve as a bridge to higher levels.

Physicians may go on to take the National Board of Echocardiography’s ASCeXAM, and nurses and sonographers may go on to take the Registered Cardiac Sonographer (RCS) exam through CCI. It’s exciting to see people take the first step towards continuing their professional development.” CCI President Jay Shafer, RCS, RVS, RVT, states, “CCI is always seeking to broaden our global awareness, and we have found that there is a dire need for educational support and a desire for recognition through credentialing, especially in emerging countries and medically underserved populations.

We are proud to announce the IEP exam as the next step in fulfilling that need.”

Meeting this need is a goal shared by all members of the Global Cardiovascular Alliance as we work together to improve cardiovascular healthcare. Palma says, “The better training we can provide, the more patients will receive better care from a variety of healthcare specialists. We need to scan more patients to pick up these diseases and get them to the experts they need.” David Adams agrees: “Our most critical role is to get the patient to treatment: that’s what we’re all seeking, and that is our focus.”

Heartbeat International is in a unique position to promote the IEP in developing countries. Adams states, “Heartbeat International reaches places that we can’t—we don’t have people on the ground in every country. They have the opportunity to tell otherwise unreachable people about this exam, and every day their teams encounter people dealing with these echo limitations.”

As fellow members of the Global Cardiovascular Alliance, our mission is to save lives through education, prevention, and treatment of cardiovascular diseases. Each member brings its own contribution to the table, whether it be education, credentialing, or treatment. Shafer says, “This is a collaborative effort: it has to be. The task is too large for a single organization to accomplish on its own, but together we can effect permanent, significant change in the lives of people around the world.”

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world. The course, designed to provide basic instruction on how to perform an echo, is now nearly complete and will soon be tested by taking it abroad. “It’s impossible for one group simply to come in and take care of the situation; the problem is too large and ongoing. We need trained people onsite, and that’s why the development of these modules is so important,” says Palma, who also chairs the ASE task force. “If I train one person, and that one person scans a thousand people, then I’ve done something significant.”

Many people performing sonography in these developing countries want recognition of their standard of performance, and educators have also found that they need a way to follow up after providing the training. Palma approached CCI to request a credential to suit their needs.

Certificate validation from the US is highly valued in these countries, as it shows the candidates have achieved some level of American standard.

CCI responded by creating the International Echo Practitioner (IEP) credentialing program, which will validate training and provide a benchmark for international sonographers. The exam, which will only be offered to practitioners outside of the United States and Canada, will be a focused, scaled-down version of CCI’s Registered Cardiac Sonographer (RCS) exam and will cover more basic echo skills. CCI offered a trial IEP exam to attendees of the 30

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PROOF HEARTBEAT SAVING LIVES

IN INDIA

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acemakers are medical marvels that have saved thousands of lives all over the world by correcting heart rhythm disorders. These lithium battery powered devices are implanted under the collar bone and connected to a cardiac chamber.

Dr Vijaya Bharat is a Cardiologist and oversees the Intensive Care Unit at the Tata Main Hospital in Jamshedpur, an industrial city in Eastern India. This hospital caters to a population of over 1.3 million in one of the poorest states in the country. Vijaya examines several patients; but when Ms. Alpana, a retired school teacher, visited her office in 2004, something was about to change. Ms. Alpana had been losing consciousness often and clearly needed a simple pacemaker that would cost about US $ 1,000. The meager resources at the disposal of her family would certainly not allow for 32

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an expense of that magnitude. Unwilling to leave the poor woman to face certain demise at an uncertain time, Vijaya researched methods to raise the necessary funds to assist her. She found out about Heartbeat International (HBI), an American organisation that distributed new pacemakers to patients around the world, who did not have the means to purchase them. While a pacemaker for Ms. Alpana was donated by a local donor Vijaya knew she had to quickly set the wheels in motion for a more sustainable programme. In January 2005, HBIâ&#x20AC;&#x2122;s 47th Pacemaker Bank was established

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in Jamshedpur under the aegis of the Tata Steel and the Rotary clubs of Jamshedpur and Chaibasa.

Since 2005, 154 heart patients not just from Jamshedpur, but also from the neighbouring states of West Bengal, Bihar and Odisha, for whom it would never have been possible to purchase a pacemaker, received them free of charge through this programme. They are regularly examined in follow up visits and seven patients whose pacemakers were detected to approach the end of battery life received free devices for the second time as well. Each of these accounts is heart-warming, but two cases deserve special mention.

Twenty two year old Dosma Liyangi, the youngest recipient of free pacemaker was diagnosed with congenital complete heart block and had syncope during her first pregnancy. A dual chamber pacemaker from the pacemaker bank was implanted in her immediately and successfully.

Though her pregnancy ended in a miscarriage, her health improved and she gave birth to two children in the next six years. Seven years after the first implantation, Dosma had the pacemaker replaced. Orphaned in childhood, Dosma feels cared for by Vijaya and International organisations.

The 99th Rotary pacemaker was implanted in a 50 year old Afghan national, Shahid. He has a small farm in Kabul and is the sole earning member of his family. He used to have syncope and was diagnosed as having intermittent complete heart block. Desperate and with an empty pocket, Shahid sought help in Kabul, Lahore, New Delhi and Kolkata before being directed to contact Vijaya for a free pacemaker. Shahid came to Jamshedpur, had the pacemaker www.HeartbeatSavesLives.org

implanted and travelled back to Afghanistan with much more confidence than when he left. It was indeed medical tourism with a difference!

Vijaya is keeping detailed records of each of these cases and is studying them. As the medical director of pacemaker bank, she has attended and presented at four Arrhythmia workshops held by HBI along with the annual conferences of the American College of Cardiology in Chicago, Atlanta and New Orleans. She has shared her research with Indian and international experts and received encouragement from the leaders in the field. Her presentation in the annual conference of the Cardiology Society of India in December 2013 was well received, and she has been invited to Melbourne, Australia to present her paper ‘Free pacemakers as peace makers – Saving lives one heart at a time’ in the World Heart Federation’s World Congress of Cardiology to be held in May 2014.

The benefits of this unique humanitarian project made accessible to so many people by Vijaya are there for all to see. Rotary International President, Sakuji Tanaka honoured her with the Rotary spouse/partner award for rendering exemplary humanitarian service in June 2013.

While the 154 beneficiaries of this pacemaker bank have sent their deepest gratitude to Tata Main Hospital, Heart Beat International and Rotary Club in letters, words and prayers, Vijaya too sends out her thanks for the opportunity she has had for all these years to make a difference in the lives of so many people.

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Together, we can do more: Every day, we save 148 lives per hour.

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