4 Athyros

΢υνδυαςμόσ ςτατίνθσ-φιμπράτθσ (Υπολειπόμενοσ καρδιαγγειακόσ κίνδυνοσ)

Β. ΑΘΥΡΟ΢, MD, FESC, FRSPH, FASA, FACS, FASB

Ιατρεία Ακθροςκλιρωςθσ και Μεταβολικοφ ΢υνδρόμου, Β’ Προπ. Πακολογικι Κλινικι ΑΠΘ, Ιπποκράτειο Νοςοκομείο, Θεςςαλονίκθ.

HAS Summer School 5 Ιουλίου 2012

Οριοκζτθςθ του υπολειπόμενου καρδιαγγειακοφ κινδφνου

Residual Cardiovascular Risk in Major Statin Trials: Standard Doses Patients Experiencing Major Coronary Events, %

100 75%

80

75%

73%

69%

62%

62%

60 40 20 0 4S

LIPID

CARE

HPS

WOS

AFCAPS / TexCAPS

N

4444

9014

4159

20 536

6595

6605

ď „LDL

-35%

-25%

-28%

-29%

-26%

-25%

Secondary

High Risk

Adapted from Libby PJ, et al. J Am Coll Cardiol, 2005:46:1225-1228.

Primary

Residual Cardiovascular Risk in Major Statin Trials Patients Experiencing Major CHD Events, %

40

CHD events occur in patients treated with statins 30

20

28.0

Placebo Statin 19.4 15.9

12.3

13.2

10.2

10

0 N ď „ LDL

4S1

LIPID2

8.7

CARE3

HPS4

4S

LIPID

CARE

HPS

4444 -35%

9014 -25%

4159 -28%

20 536 -29%

Secondary 14S

11.8

Group. Lancet. 1994;344:1383-1389.

2LIPID Study Group. N Engl J Med. 1998;339:1349-1357.

3Sacks FM, et al. N Engl J Med. 1996;335:1001-1009.

High Risk 4HPS

10.9

7.9

6.8

5.5

WOSCOPS5 AFCAPS/ WOS AFCAPS / TexCAPS6 TexCAPS 6595 6605 -26% -25% Primary

Collaborative Group. Lancet. 2002;360:7-22.

J, et al. N Engl J Med. 1995;333:1301-1307.

6 Downs JR, et al. JAMA. 1998;279:1615-1622.

5Shepherd

Residual CVD Risk With Statin Therapy: Standard Doses in Diabetes

30

HPS: Patients With Diabetes

CARDS (diabetes) 16

25.1

14

20.2

22% Risk Reduction

20

15

10

78% Residual Risk

5

12

Event Rate, %

Event Rate, %

25

13.4

10

9.4

32% Risk Reduction

8

6 4

68% Residual Risk

2 0

0

Placebo Simvastatin

Placebo Atorvastatin

STENO-2: Composite Endpoint of Death from CV Causes, Nonfatal MI, CABG, PCI, Nonfatal Stroke, Amputation, or Surgery for PAD

Primary Composite Endpoint (%)

60

Conventional Therapy

50

53% Reduction

Hazard ratio = 0.47 P=0.008

40 30 20

Intensive Therapy

10 0

0

12 24 36 48 60 72 Months of Follow-up

GĂŚde P et al. N Engl J Med 2003;348:383-393.

84

96

R3i: Ο ζηόχος  Ο πεξηνξηζκόο ησλ ζεκαληηθώλ παξάπιεπξσλ παξαγόλησλ θηλδύλνπ πνπ κπνξνύλ λα πξνθαιέζνπλ ΜΑΚΡΟ-αγγεηαθέο εθδειώζεηο θαη ΜΙΚΡΟ-αγγεηαθέο επηπινθέο. Ο θίλδπλνο απηόο ζπλερίδεη λα είλαη ππαξθηόο ζηνπο πεξηζζνηέξνπο αζζελείο παξά ηηο ζύγρξνλεο πξαθηηθέο πνπ αθνινπζνύληαη θαηά ηελ αγσγή πγείαο, κεηαμύ ησλ νπνίσλ πεξηιακβάλεηαη θαη ε κείσζε ηεο LDL-X θαζώο θαη ν εληαηηθόο έιεγρνο ηεο αξηεξηαθήο πίεζεο θαη ηνπ ζαθράξνπ ηνπ αίκαηνο.  Ο ζηόρνο ηνπ R3i ζηελ νιηζηηθή αληηκεηώπηζε αζζελώλ πςεινύ θαξδηαγγεηαθνύ θηλδύλνπ κπνξεί λα επηηεπρζεί κε ηε ζπκκεηνρή ησλ επαγγεικαηηώλ πγείαο θαη πεξίζαιςεο, ώζηε λα βειηησζεί ζεκαληηθά ηόζν ε πνηόηεηα όζν θαη ε δηάξθεηα δσήο εθαηνκκπξίσλ ζπλαλζξώπσλ καο.

R3i: Τοπικές οργανώζεις ζε εθνικό επίπεδο

Lituania Latvia

Canada

Germany Poland Czech R Belgium Hungary

Ireland UK

Switzerland US

France

Portugal

Spain

Austria

Italy

Algeria Morocco

Russia

Bulgaria Romania

Croatia

Japan

Slovakia

Greece

China

Turkey

Tunisia

Hong Kong

Jordan Egypt

Emirates

Mexico Saudi Arabia

Korea

Kuwait UAE

Thailand

Qatar 3

Taiwan

Vietnam

Malaysia

South America ( in development)

Indonesia Singapore Philippines

South Africa

Australia

8

R3i: Οξγάλσζε θαη πξνγξάκκαηα R3i Organization

1 Δηεζλείο Οξγαλσηηθή Επηηξνπή *

2 Εζληθή Οξγαλσηηθή Επηηξνπή

3 Εζληθέο Επηηξνπέο

Residual Risk Reduction programs

1

ISC

NSCs

΄Εξεπλα

Δηεζλείο επηδεκηνινγηθή κειέηε, εξεπλεηηθά πξνγξάκκαηα

2

Εθπαίδεπζε

Εθπαηδεπηηθά πξνγξάκκαηα, ΢πλερνδόκελε Ιαηξηθή Εθπαίδεπζε, ηζηόηνπνο webinars

3

Επηθνηλσλία

Δεκνζηεύζεηο, θαηεπζπληήξηε ο νδεγίεο, ζεξαπεπηηθνί αιγόξηζκνη

National Specialists

PCPs

Αιιειεπίδξαζε κε ηελ ηαηξθή θνηλόηεηα * : Καξδηνιόγνη, Δηαβεηνιόγνη, Ληπηδηνιόγνη, Γεληθνί ηαηξνί, Παζνιόγνη, Ελδνθξηλνιόγνη, Επηδεκηνιόγνη, Οθζαικίαηξνη

9

R3i: Σν Τπόβαζξν  Παξά ηελ απνηειεζκαηηθόηεηα ησλ ζύγρξνλσλ πξαθηηθώλ πνπ αθνινπζνύληαη θαηά ηελ αγσγή πγείαο, κεηαμύ ησλ νπνίσλ πεξηιακβάλεηαη θαη ε επίηεπμε ηνπ ζηόρνπ γηα ηελ κείσζε ηεο LDL-C, νη αζζελείο παξακέλνπλ αθόκε εθηεζεηκέλνη εμαηηίαο ηνπ Τπνιεηπόκελνπ Kαξδηαγγεηαθνύ θηλδύλνπ ν νπνίνο νδεγεί ζε:  Μαθξν-αγγεηαθέο επηπινθέο  ΄Εμθραγμα ηου μυοκαρδίου  Αγγειακό Εγκεθαλικό επειζόδιο

 Μηθξν-αγγεηαθέο επηπινθέο  Αμθιβληζηροειδοπάθεια

 Νεθροπάθεια  Νευροπάθεια

10

Ο Υπολειπόμενος Καρδιαγγειακός Κίνδυνος έχει

ιδιαίτερη σημασία για την αντιμετώπιση του Σ2ΣΔ. Κύξηα αηηία ηύθισζεο ζηνπο ελήιηθεο (24.000 λέα πεξηζηαηηθά θάζε ρξόλν ζηηο ΗΠΑ) Δηαβεηηθή ακθηβιεζηξνεηδνπάζεηα

Κύξηα αηηία λεθξνπάζεηαο ηειηθνύ ζηαδίνπ ζηνπο ελήιηθεο (44% λέα πεξηζηαηηθά αλά έηνο).

Αύμεζε θαηά 2 έσο 4 θνξέο ησλ αγγεηαθώλ εγθεθαιηθώλ λνζεκάησλ θαη επεηζνδίσλ Αγγεηαθό εγθεθαιηθό επεηζόδην

8 ζηνπο 10 δηαβεηθνύο αζζελείο πεζαίλνπλ από θαξδηαγγεηαθά επεηζόδηα ελώ ην πξνζδόθηκν επηβίσζεο κεηώλεηαη θαηά 5-10 έηε.

Δηαβεηηθή λεθξνπάζεηα Καξδηαγγεηαθό λόζεκα

Κύξηα αηηία αθξσηεξηαζκώλ ησλ θάησ άθξσλ πνπ δελ είλαη ζπλέπεηα ηξαπκαηηζκώλ (60% λέα πεξηζηαηηθά αλά έηνο)

Δηαβεηηθή λεπξνπάζεηα

NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2006.

Η ρακειή ηηκή ηεο HDL-c απνηειεί ζεκαληηθή ζπληζηώζα ηνπ Τπνιεηπόκελνπ Καξδηαγγεηαθνύ Κηλδύλνπ γηα ηηο ΜΑΚΡΟαγγεηαθέο επηπινθέο Μειέηε PROCAM : Η ρακειή ηηκή ηεο HDL-C είλαη έλαο αλεμάξηεηνο πξνγλσζηηθόο δείθηεο ζηεθαληαίαο λόζνπ αθόκε θαη όηαλ ε ηηκή ηεο LDL-C είλαη ρακειή1

1 – Assmann G et al. Eur Heart J Suppl 2006;8(SupplF):F40-6.

12

Σα πςειά ηξηγιπθεξίδηα απνηεινύλ ζεκαληηθή ζπληζηώζα ηνπ Τπνιεηπόκελνπ Καξδηαγγεηαθνύ Κηλδύλνπ γηα ΜΑΚΡΟ-αγγεηαθέο επηπινθέο.

PROVE IT-TIMI 22 study: Παξά ηελ επίηεπμε ηηκώλ LDL-C <70 mg/dL (1.8 mmol/L) κε πςειέο δόζεηο ζηαηηλώλ, νη αζζελείο κε ηηκέο ηξηγιπθεξηδίσλ ≥200 mg/dL (2.3 mmol/L) παξνπζηάδνπλ 56% αύμεζε ζηελ πηζαλόηεηα ζαλάηνπ, εκθξάγκαηνο ηνπ κπνθαξδίνπ (ΕΜ) ή νμένο ζηεθαληαίνπ ζπλδξόκνπ (Ο΢΢)1

1 – Miller M et al. J Am Coll Cardiol 2008;51:724-30.

14

Δίαιτα

Φάρμακα

΢ΤΝΟΛΙΚΗ ΒΔΛΣΙΩ΢Η ΣΟΤ ΛΙΠΙΔΑΙΜΙΚΟΤ ΠΡΟΥΙΛ

 ΦΟΡΗΓΗ΢Η ΢ΤΝΔΤΑ΢ΜΟΤ ΤΠΟΛΙΠΙΔΑΙΜΙΚΩΝ ΥΑΡΜΑΚΩΝ  ΦΟΡΗΓΗ΢Η ΢ΣΑΣΙΝΩΝ ΜΔ ΑΛΛΑ ΥΑΡΜΑΚΑ ΠΟΤ TRG/ HDL CHOL

Figure 1 Concepts in the pathogenesis of myopathy associated with lipid-modifying therapies

Reprinted by permission from Macmillan Publishers Ltd: Clin. Pharmacol. Ther. Laaksonen, R. On the mechanisms of statin-induced myopathy. 79, 529–531 ©2006

Jacobson, T. A. (2009) Myopathy with statin–fibrate combination therapy: clinical considerations Nat. Rev. Endocrinol. doi:10.1038/nrendo.2009.151

Fibrates in Combination With Statins in the Management of Dyslipidemia

The Journal of Clinical Hypertension Volume 8, Issue 1, pages 35-41, 31 JAN 2007 DOI: 10.1111/j.1524-6175.2005.05278.x http://onlinelibrary.wiley.com/doi/10.1111/j.1524-6175.2005.05278.x/full#f2

Fibrates in Combination With Statins in the Management of Dyslipidemia

The Journal of Clinical Hypertension Volume 8, Issue 1, pages 35-41, 31 JAN 2007 DOI: 10.1111/j.1524-6175.2005.05278.x http://onlinelibrary.wiley.com/doi/10.1111/j.1524-6175.2005.05278.x/full#f1

Figure 2 Changes in geometric mean plasma concentrations of a | rosuvastatin after dosing of rosuvastatin alone and rosuvastatin in combination with fenofibrate; and b | fenofibrate after dosing of fenofibrate alone and in combination with rosuvastatin

Reprinted from Martin, P. D. et al. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin. Ther. 25, 459â&#x20AC;&#x201C;471, Š 2003, with permission from Excerpta Medica, Inc Jacobson, T. A. (2009) Myopathy with statinâ&#x20AC;&#x201C;fibrate combination therapy: clinical considerations Nat. Rev. Endocrinol. doi:10.1038/nrendo.2009.151

Figure 3 Number of cases of rhabdomyolysis reported per million prescriptions dispensed of a | cerivastatin in combination with fenofibrate or gemfibrozil and b | statins other than cerivastatin in combination with fenofibrate or gemfibrozil

Reprinted from Am. J. Cardiol. 95, Jones, P. H. & Davidson, M. H. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin, 120â&#x20AC;&#x201C;122 Š2005, with permission from Elsevier Jacobson, T. A. (2009) Myopathy with statinâ&#x20AC;&#x201C;fibrate combination therapy: clinical considerations Nat. Rev. Endocrinol. doi:10.1038/nrendo.2009.151

Table 2 Pharmacologic profiles of various statins and fibrates

Informa Healthcare © Jacobson T. A. Combination lipid-lowering therapy with statins: safety issues in the postcerivastatin era. Expert Opin. Drug. Saf. 2, 269–286 (2003) Jacobson, T. A. (2009) Myopathy with statin–fibrate combination therapy: clinical considerations Nat. Rev. Endocrinol. doi:10.1038/nrendo.2009.151

National Kidney Foundation: Stages of CKD (Age >20 Years) Stage

Description

GFR (mL/min/1.73 m2)

Clinical term

1

Kidney damage with normal or  GFR

>90

2

Mild  GFR

60-89

3

Moderate  GFR

30-59

CKD

4

Severe  GFR

15-29

Advanced CKD

5

Kidney failure

<15 or dialysis

ESRD

NKF Clinical Practice Guidelines for CKD. Am J Kid Dis 2002;39:S1-S26631

Atherosclerosis 2001 155;263â&#x20AC;&#x201C;264

Statin-fibrate combinations in patients with combined hyperlipidemia

Athyros VG, et al. Atherosclerosis 2001 155;263â&#x20AC;&#x201C;264

Statin-fibrate combinations in patients with combined hyperlipidemia

Athyros VG, et al. Atherosclerosis 2001 155;263â&#x20AC;&#x201C;264

Statin-fibrate combinations in patients with combined hyperlipidemia

Athyros VG, et al. Atherosclerosis 2001 155;263â&#x20AC;&#x201C;264

Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia

Athyros VG, et al. Diabetes Care 25:1198â&#x20AC;&#x201C;1202, 2002

Statin Fibrate Combination on 10-year CVD risk in T2DM Baseline 10-year CVD risk

Intervention

25 20 15 %

10

-80%

5 0 Fenofibrate

Atorvastatin

p<0.0001 vs baseline for all

Athyros VG, et al. Diabetes Care 25:1198â&#x20AC;&#x201C;1202, 2002

Combined

METABOLISM Clinical and Experimental

Targeting vascular risk in patients with metabolic syndrome but without diabetes

Athyros et al. Metabolism 2005;54:1065-74.

Targeting Cardiovascular Risk in Patients with Metabolic Syndrome Atorvastatin

Fenofibrate

Combination

30 20 10 0 -10 -20 -30 -40 -50 TC

LDL-C HDL-C 12 months

Athyros et al. Metabolism 2005;54:1065-74.

TGs

Targeting Cardiovascular Risk in Patients with Metabolic Syndrome without Diabetes Fenofibrate n=100

Atorvastatin n=100

Combination n=100

0

-20

% -40

-60

-80

LDL-C

hsCRP

12 months Athyros et al. Metabolism 2005;54:1065-74.

PROCAM 10-year Risk

Efficacy and safety of fenofibric acid in combination with rosuvastatin in patients with mixed dyslipidaemia

Jones PH, et al. Atherosclerosis 2009 May;204:208-15.

Efficacy and safety of fenofibric acid in combination with atorvastatin in patients with mixed dyslipidaemia

Goldberg AC, et al. Am J Cardiol 2009 103(4):515-22.

AC17

Assessing the macro- and microvascular benefits of statin/fibrate combination therapy ACCORD LIPID

AC18

ACCORD Lipid The question asked

ď&#x201A;§ In the context of good glycemic control, does a therapeutic strategy that uses a fibrate to increase HDLC and lower triglyceride levels together with a statin to lower LDL-C reduce the rate of CVD events compared with a strategy that uses a statin only?

Buse JB et al. Am J Cardiol. 2007;99(12A):21i-33i.

AC24

Baseline characteristics ACCORD LIPID

AC25

Baseline characteristics Demographics & risk factors Simvastatin + Fenofibrate (n=2,765)

Simvastatin + Placebo (n=2,753)

Overall (n=5,518)

Age, mean (yrs)

62

62

62

Women, no. (%)

851 (31)

843 (31)

1,694 (31)

White

1,909 (69)

1,865 (68)

3,774 (68)

Black

392 (14)

442 (16)

834 (15)

213 (8)

194 (7)

407 (7)

410 (15)

393 (14)

803 (15)

Secondary prevention (%)

37

37

37

Median diabetes duration (yrs)

10

9

9

Demographics

Race/ethnicity , no. (%)

Hispanic

Risk factors Current smoker, no (%)

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

AC27

Baseline characteristics Lipids

Simvastatin + Fenofibrate (n=2,765)

Simvastatin + Placebo (n=2,753)

Overall (n=5,518)

Mean total cholesterol

175 (4.5)

176 (4.5)

175 (4.5)

Mean LDL-C

100 (2.6)

101 (2.6)

101 (2.6)

Mean HDL-C

38 (1.0)

38 (1.0)

38 (1.0)

Median triglycerides

164 (1.9)

160 (1.8)

162 (1.8)

114-232 (1.28-2.61)

112-227 (1.252.55)

113-229 (1.26-2.57)

Baseline lipids

Interquartile range Data presented as mg/dL (mmol/L)

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

AC28

Lipids changes ACCORD LIPID

28

AC29

ACCORD Lipid Changes in total cholesterol and LDL-C throughout the study Reduction in total cholesterol was significantly greater in the combination arm

Reduction in LDL-C was similar for both arms (mean 80 mg/dL)

Change in mean total cholesterol

Change in mean LDL-C

180

120

Mean (mg/dL)

Mean (mg/dL)

Placebo 160

140

Fenofibrate

Placebo

100

Fenofibrate

80

p = 0.02

120

p = 0.16

60

0

0

0

1

2

3

4

5

6

7

0

1

2

Years

4

5

6

7

2361 2364

1477 1480

796 801

248 243

Years

No. of Patients

Fenofibrate 2747 Placebo 2735

3

No. of Patients

2593 2591

2505 2484

2417 2375

2361 2364

1478 1480

796 801

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

248 243

Fenofibrate 2747 Placebo 2735

2593 2591

2505 2484

2417 2375

AC30

ACCORD Lipid Changes in HDL-C and triglycerides throughout the study Increase in HDL-C was significantly greater in the combination arm

Reduction in triglycerides was significantly greater in the combination arm

Change in mean HDL-C

Change in mean triglycerides

43

Mean (mg/dL)

Mean (mg/dL)

Fenofibrate

41 40 39

Placebo

38

140

120

p = 0.01

37 0

p < 0.0001

Placebo

160

42

Fenofibrate 100 0

0

1

2

3

4

5

6

0

7

1

2

No. of Patients

Fenofibrate 2747 Placebo 2735

3

4

5

6

7

2361 2364

1478 1480

796 801

248 243

Years

Years No. of Patients

2593 2591

2505 2484

2417 2375

2361 2364

1477 1480

796 801

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

248 243

Fenofibrate 2747 Placebo 2735

2593 2591

2505 2484

2417 2375

AC35

Macrovascular Outcomes ACCORD LIPID

35

AC36

ACCORD Lipid primary macrovascular outcome (CV death + nonfatal MI + nonfatal stroke) Absence of difference between groups

Proportion with Event (%)

100

20

80

Placebo

10

Fenofibrate

60 0 0

40

1

2

3

4

5

6

7

8

p=0.32

20

0 0

1

2

3

4

5

6

7

8

412 395

249 245

137 131

Years

No. At Risk Fenofibrate Placebo

2765 2644 2565 2485 1981 1160 2753 2634 2528 2442 1979 1161

ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

AC37

Secondary macrovascular outcomes ACCORD LIPID

AC38

ACCORD Lipid Prespecified secondary macrovascular outcomes Outcomes

Simvastatin + Fenofibrate (n=2765)

Simvastatin + Placebo (n=2753)

Hazard Ratio (95% Cl)

p value

no. of events

rate/ yr

no. of events

rate/ yr

Primary outcome plus revascularization or hospitalization for CHF

641

5.4

667

5.6

0.94 (0.85-1.05)

0.30

Major coronary disease eventâ&#x20AC;

332

2.6

353

2.8

0.92 (0.79-1.07)

0.26

Nonfatal MI

173

1.3

186

1.4

0.91 (0.74-1.12)

0.39

Any

51

0.4

48

0.4

1.05 (0.71-1.56)

0.80

Nonfatal

47

0.4

40

0.3

1.17 (0.76-1.78)

0.48

203

1.5

221

1.6

0.91 (0.75-1.10)

0.33*

99

0.7

114

0.8

0.86 (0.66-1.12)

0.26

120

0.9

143

1.1

0.82 (0.65-1.05)

0.10

Stroke

Death From any cause From CVD Fatal or nonfatal CHF

* P values were adjusted for interim monitoring. â&#x20AC; A major coronary disease event was defined as a fatal coronary event, nonfatal MI, unstable angina.

AC41

Primary macrovascular outcomes in prespecified subgroups ACCORD LIPID

AC48

1. ACCORD Lipid results reinforce the residual risk hypothesis  Despite achieving a mean LDL-C of 80 mg/dL, patients in the atherogenic dyslipidemia* subgroup had a 70% higher rate of major CV events compared to those without atherogenic dyslipidemia Proportion with CV event

20

17.32%

15

+70%

10

10.11% 5

0

With atherogenic dyslipidemia* (n=456)

Without atherogenic dyslipidemia (n=2,284)

Patients on simvastatin alone *TG ≥204 mg/dL and HDL-C ≤34 mg/dL ACCORD Study Group. N Engl J Med March 14, 2010. Epub.

+ 70%

Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data Alexander Tenenbaum1,2,3,4*, Diego Medvedofsky2, Enrique Z. Fisman4, Liudmila Bubyr3, Shlomi Matetzky2,3, David Tanne3, Robert Klempfner1,2,3, Joseph Shemesh1, Ilan Goldenberg1,2,3,5 1 Cardiac Rehabilitation Institute, The Chaim Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 2 Leviev Heart Institute, The Chaim Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 3 The Israeli Society for the Prevention of Heart Attacks, The Chaim Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 4 Cardiovascular Diabetology Research Foundation, Holon, Israel, 5 Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York, United States of America

Conclusion

A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy.

Tenenbaum A, Medvedofsky D, Fisman EZ, Bubyr L, et al. (2012) Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data. PLoS ONE 7(4): e35298. doi:10.1371/journal.pone.0035298 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035298

â&#x20AC;˘Figure 2. Rate (%) of 30-day Major Adverse Coronary Events (MACE) among the study patients according to the age, gender, level of HDL cholesterol, triglycerides, smoking status, presence of diabetes and hypertension.

Tenenbaum A, Medvedofsky D, Fisman EZ, Bubyr L, et al. (2012) Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data. PLoS ONE 7(4): e35298. doi:10.1371/journal.pone.0035298 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035298

•

Figure 1. Kaplan-Meier curve of mortality rate during one year follow-up for 7243 patients from years 2000–2008 (combined fibrate/statin therapy vs. statin monotherapy, p log-rank = 0.066).

Tenenbaum A, Medvedofsky D, Fisman EZ, Bubyr L, et al. (2012) Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data. PLoS ONE 7(4): e35298. doi:10.1371/journal.pone.0035298 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035298

â&#x20AC;˘ Table 6. Effect of combined fibrate/statin treatment vs. statin monoterapy on 30-day Major Adverse Coronary Events (MACE) in risk subgroups: odds ratio and 95% confidence interval (CI).

Tenenbaum A, Medvedofsky D, Fisman EZ, Bubyr L, et al. (2012) Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data. PLoS ONE 7(4): e35298. doi:10.1371/journal.pone.0035298 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035298

΢ΤΜΠΕΡΑ΢ΜΑΣΑ Ο ςυνδυαςμόσ ςτατίνθσ-φαινοφιμπράτθσ είναι αςφαλισ και αποτελεςματικόσ Ελαττώνει τθν ακθρογόνο δυςλιπιδαιμία και ζχει ωσ αποτζλεςμα τθν ςθμαντικι ελάττωςθ των καρδιαγγειακών ςυμβαμάτων ςτουσ αςκενείσ αυτοφσ. Επειδι θ φαινοφιμπράτθ βελτιώνει τισ μικροαγγειακζσ βλάβεσ του διαβιτθ αντιμετωπίηει αποτελεςματικά και το ςκζλοσ αυτό του υπολειπόμενου καρδιαγγειακοφ κινδφνου.