SHA24/081001

National Heart Association of Malaysia(NHAM) International Collaboration Session: Resistant Hypertension

Epidemiology and Medical Therapy, Malaysia Perspective Wan Azman Wan Ahmad FRCP, FAMM, FNHAM, FAsCC, FAPSIC, FESC, FSCAI, FACC

Professor of Medicine and Head of Cardiology University Malaya Medical Centre Kuala Lumpur, Malaysia GHA 10/SHA 24 Joint Scientific Conference, Kingdom of Saudi Arabia, 13th-16th Feb 2013

Disclosure I have no conflict of interest in the context of this presentation

Lecture Outline • • • • • •

Magnitude of Hypertension in Malaysia Treatment and Control Challenges in Hypertension treatment Resistant Hypertension Case Studies Future Development

Magnitude of Hypertension in Malaysia The Third National Health and Morbidity Survey (NHMS III) 2006 - A research project sponsored by Ministry of Health Malaysia • Multi purpose survey designed to describe the health status, health related behaviour and health services utilization for a representative sample of the population of Malaysia • For NHMS III component of blood pressure 33,976 individuals aged 18 or older were eligible

Hypertension • Hypertension is defined as an average of two blood pressure readings at single occasion with: a systolic BP of ≥ 140 mmHg, and/or a diastolic BP of ≥ 90 mmHg, or Currently on antihypertensive medication

• Standard definition used by NHANES, JNC, National surveys

Table 1: Characteristics of respondents for hypertension module of NHMS III (N= 33,976) n

%

Adjusted*%

15,209 18,767

44.8 55.2

50.6 49.4

1,688 7,492 7,107 7,313 5,516 3,072 1,788

5 22.1 20.9 21.5 16.2 9 5.3

6.7 28.4 24.9 18.8 10.9 6.4 3.9

Sex Male Female

Age 18-19 20-29 30-39 40-49 50-59 60-69 ≼70

*adjusted to Malaysian population by age, sex and race

Table 1: Characteristics of respondents for hypertension module of NHMS III (N= 33,976) n

%

Adjusted*%

Ethnicity Malay Chinese Indian Bumiputra Sabah Bumiputra Sarawak Others Foreigner

17995 6771 2685 2473 1302 586 2164

53.0 19.9 7.9 7.3 3.8 1.7 6.4

49 24.8 7.4 5.6 4.1 0.6 8.5

Urban/Rural Urban Rural

20055 13921

59 41

62.1 37.9

*adjusted to Malaysian population by age, sex and race

Prevalence of HPT by race amongst Malaysian residents aged ≼ 18 years in 2006 (N=33,976) 35 34

34.4 33.9

Prevalence (%)

33 32 31

32.4

32.2

31.1

30 29

29.4

28 27 26 All races

Malay

Chinese

Ethnicity

Indians

Bumiputra Sabah

Bumiputra Saraw ak

Prevalence of HPT by sex amongst Malaysian residents aged ≼ 18 years in 2006 (N=33,976) 33.5 33.3

33

Prevalence (%)

32.5 32

32.2

31.5 31 31

30.5 30 29.5 Overall

Male

Female

Gender

Prevalence of hypertension in urban vs. rural area amongst Malaysian residents aged ≼ 18 years in 2006 (N=33,976) 40 35 36.9

Prevalence (%)

30 25

29.3

20 15 10 5 0 Urban

Rural

Area

Estimated number of HPT population by sex and race amongst Malaysian residents aged ≼ 18 years in 2006* Age (Years)

Sex, million population (95% CI) Male

Female

Both sexes

All races

2.2 (2.1, 2.2)

2.6 (2.5, 2.7)

4.8 (4.6, 4.9)

Malay

1.2 (1.1, 1.2)

1.5 (1.5, 1.6)

2.7 (2.6, 2.8)

Chinese

0.5 (0.5, 0.6)

0.5 (0.5, 0.6)

1.0 (1.0, 1.1)

Indians

0.2 (0.1, 0.2)

0.2 (0.2, 0.2)

0.4 (0.3, 0.4)

Other Bumis**

0.2 (0.2, 0.3)

0.2 (0.2, 0.3)

0.5 (0.4, 0.5)

*Rounded up to the closest 0.1 million population ** Comprises of all Non Malay Bumiputras

Prevalence of HPT by race amongst Malaysian residents aged ≼ 30 years in 2006 (N=24,796) 50 45

45.4 42.6

40.6

40

40

34.4

Prevalence (%)

35

31.1

30 25 20 15 10 5 0 All races

Malay

Chinese

Ethnicity

Indians

Bumiputra Sabah

Bumiputra Sarawak

Prevalence of HPT by sex amongst Malaysian residents aged ≼ 30 years in 2006 (N=24,796) 44 43.4

43.5

Prevalence (%)

43 42.6 42.5

42

41.7

41.5 41

40.5 Overall

Male

Gender

Female

Awareness, Treatment and Control of HPT by sex amongst Malaysian Residents aged ≼ 30 years, 2006 Sex, % (95%CI) Male

Female

Both sexes

Hypertensives (N=11,673) Aware

31.5 (30.1,32.9)

40.0 ( 38.7,41.2)

35.8 (34.8, 36.8)

Currently Treated

27.3 (26.0, 28.6)

35.4 (34.2, 36.7)

31.4 (30.4,32.3)

7.7 (7.0, 8.6)

8.7 (8.0, 9.5)

8.2 (7.7, 8.8)

Controlled

Treatment and Control of HPT by sex amongst Those Aware of Hypertension Status aged ≼ 30 years, 2006 (N= 3,927) Sex, % (95%CI) Male

Female

Both sexes

Aware & treated

86.5 (84.7, 88.1)

88.7 (87.3.89.9)

87.7 (86.6.88.7)

Treated & Controlled

28.4 (26.0, 30.9)

24.7 (22.9, 26.5)

26.3 (24.8, 27.8)

The ‘Malaysian Rule’ All hypertensive 64%

36% 69%

Aware 31%

92%

Treated 8% Controlled

Magnitude of Hypertension in Malaysia L. Rampal, S.Rampal, M.Z. Azhar, A.R. Rahman.

Public Health (2008) 122, 11-18

• Prevalence, awareness, treatment and control of Hypertension in Malaysia: A national study of 16,440 subjects. • A cross-sectional study conducted in all states of Malaysia to determine the prevalence, awareness, treatment and control of Hypertension (study was conducted 2004)

Results • The prevalence of HPT for respondents age ≥ 30yrs was 40.5%(42.6% in NHMS III) • Males 29.6% vs females 26.0% • Multivariate logistic regression showed the odds of having Hypertension – Increasing age – Males – Family history of HPT – Increasing body mass index (BMI ≥ 30) – Non-smoker – Decreasing level of education

Results • Only 34.6% of the subjects with HPT were aware of their Hypertension status (36% in NHMS III) • 32.4% were taking antihypertensive medication (31% in NHMS III) • Among those taking antihypertensive medication only 26.8% had their blood pressure under control.

(26.3% in NHMS III) • Blood pressure control was only achieved in 8.6% of the respondents who has HPT (8% in NHMS III)

National Cardiovascular Disease Database ACS Registry (est. 2006) PCI Registry (est. 2007)

NCVD-ACS Registry Active Sites HTF HSB

QEH

HRPZ II

PH

HPRPB HTAA UMMC IJN HKL HTAR

SGH

HTJ HM

HSAJB NCVD-ACS Registry, Malaysia (Established 1st January 2006

Total sites = 15

NCVD-PCI Registry Active Sites QEH (2008)

SBH PH

KPJSSH SH

SGH

UMMC IJN HUKM MMC (2009)

HSAJB

Total sites = 11

NCVD-PCI Registry, Malaysia ( Established 1st January 2007 )

PUBLICATIONS

Demographics 2006 (N=3442)

2007 (N=3645)

2008 (N=2848)

Age Mean Âą sd Min, Max

59 + 12 years 21, 100 years

25, 95 years

21, 94 years

Male

75 %

77 %

75 %

Female

25 %

23 %

25 %

Gender

Malaysians develop ACS at a younger age (mean age 59 yrs old) when compared to people in Thailand (65 yrs), mainland China (63 yrs) and western countries (Grace Registry 66 yrs)

Percentage of CV Risk Factors 2006 (N=3442)

2007 (N=3645)

2008 (N=2848)

Dyslipidaemia

33

35

31

Hypertension

61

63

56

Diabetes

44

44

39

Family History of premature CVD

12

13

9

MI history

16

18

13

Documented CAD

15

18

15

New onset angina (< 2 weeks)

45

53

48

Chronic angina (onset > 2 weeks ago)

15

11

8

Chronic Lung Disease

4

3

3

Renal disease

7

6

5

Peripheral vascular disease

1

1

1

Cerebrovascular disease

4

3

3

Heart Failure

8

7

5

Annual Report of the Acute Coronary Syndrome (ACS) Registry 2006 - 2008

 10,602 patients  11,498 PCI Procedures  Mean Age 57 years old  Risk factors • hypertension (73.6%) • dyslipidemia (73.4%) • diabetes (46.2%) • smoking (47.1%)

National Essential Hypertension Audit Institute of Health Management, Ministry of Health ( IHM MOH 2006 )

Rates of BP control by Hospital/clinic • Hospital with specialist

31.2%

• Hospital without specialist

26.6%

• Clinics with FMS/ MO

28.8%

• Clinics without FMS/MO

26.9%

National Essential Hypertension Audit Institute of Health Management, Ministry of Health ( IHM MOH 2006 )

Rates of BP control by ethnicity • Malay

24.3%

• Indians

30.8%

• Chinese

37.6%

• Others

30.8%

National Essential Hypertension Audit Institute of Health Management, Ministry of Health ( IHM MOH 2006 )

Rates of BP control by age • 30-39

19.4%

• 40-49

27.1%

• 50-59

29.1%

• >60

29.2%

Points to ponder! Why Malaysian patients have poor BP control

• Patients’ non compliance/denial • Doctors not sure when to treat and what the treatment goals are • Doctors not using the right drug/drugs • Patients has undiagnosed secondary hypertension or complications of hypertension which makes optimum control difficult

Strategies to improve management of hypertensive patients in Malaysia?

Soft copy available at: www.moh.gov.my www.acadmed.org.my www.msh.org.my

Classification of blood pressure for adults age 18 and older: Malâ&#x20AC;&#x2122; CPG 2008

Ref: Lim TO, Ding LM, Goh BL, et al. Distribution of Blood Pressure in a National Sample of Malaysian Adults. Med J Malaysia 2000;55:90-107.

Source: Clinical Practice Guideline on Management of Hypertension 2008 (3 rd Edition).

Treatment targets Mal’ CPG 2008 • <140/85 mmHg for most • < 130/80 mmHg for patients with diabetes or chronic kidney disease • < 125/75 mmHg for patients with proteinuria > 1g/24hours

Prevalence of Hypertension in Malaysia (NHMS IV 2011) Year

Age group Definition of hypertension Prevalence

1986 NHMS I

1996 NHMS II

1996 NHMS II

≥ 25

≥ 18

≥ 30

≥ 18

≥ 30

> 18

≥160/95

≥140/90

≥140/90

≥140/90

≥ 140/90

≥ 140/90

14.4%

29.9%

32.9%

32.2%

42.6%

*32.7%

Refer * •12.8% are known to have hypertension •19.8% are previously undiagnosed with hypertension

2006 2006 NHMS III NHMS III

2011 NHMS IV

Target BP better in NHMS IV Only 26% achieved target BP while on treatment (NHMS III- 2006) NHMS IV -2011 34.8% achieved target BP • • • • • • •

BP controlled was seen highest in Age > 60 years Males Chinese Those with secondary education Retirees Those with earning > RM5000 per month Urban residents

Malaysian Untreated Hypertensives (Acta Cardiol. 1999;54:277-282 )

NT SBP * 120 (112-130) DBP* 80 ( 78-82 ) MAP * 94 ( 91-97 ) PWV* 8.8 (8.3- 9.6)

HT 169 ( 160-180 ) 100 ( 100-110 ) 123 ( 119-130 ) 11.7 ( 10.9- 12.9 )

Our population most likely needs combination antihypertensive agents

Malaysian Untreated Hypertensives (Acta Cardiol. 1999;54:277-282 )

NT

HT

Se Na *

142.18 + 0.78

146.83 + 2.30

UNaV *

140.58 + 15.65

100.55 + 17.28

Se i Ca*

1.25 + 0.01

1.17 + 0.01

PRA

0.89 + 0.19

0.79 + 0.2

PRC

3.09 + 0.74

4.23 + 1.43

Se Aldo

275 + 21.51

257 + 16.22

“Malaysian hypertensives are salt retainers “ “ Malaysian hypertensives are normoreninaemic hypertensives “

Effective Combinations in Malaysia - Retrospective Review of Record ( Asia Pac J Pharmacol.; 2001:17-24 )

SBP * DBP * dSBP * dDBP

Diuretics ( n=100 ) 140 +2 85+1 30+3 13+2

No Diuretics ( n=100 ) 151+3 88+1 21+3 13+2

Effective Combinations in Malaysia Diuretics

Controlled

66%

No Diuretics

38%

p < 0.0001

What predicts BP control ?

By univariate analysis • Statin on admission • Presence of IHD • Diuretics on admission • ACEI on admission • > 2 drugs

Odds 2.53 2.21 2.12 1.97 1.92

p 0.000 0.001 0.002 0.006 0.007

Malaysian Statistics on Medicine 2005 â&#x20AC;˘ reported that 81% of hypertensive patients were on mono-therapy â&#x20AC;&#x201C; hardly sufficient to achieve BP control

Percentage of Patients Requiring ≥ 2 Antihypertensive Drugs to Reach BP Targets 100

90

90

Percent

80 70 60

73

78

63

60

50 40 30 20 10 0

HOT

LIFE

1. HOT: Hansson et al. Lancet. 1998;351:1755–62.

2. LIFE: Dahlöf et al. Lancet.

Lancet. 2002;359:995-1003.

3. ALLHAT: Cushman et al. J Clin Hypertens.

2002;4:393–404.

ALLHAT

CONVINCE

ASCOT

4. CONVINCE: Black et al. JAMA. 2003;289:2073-2082.

5. ASCOT: Dahlöf et al. Lancet. 2005;366:895-906.

A typical Malaysian Hypertensive - Back to Reality !

• Diagnosed late • Has other concomitant cardiovascular risk factors • Has complications of hypertension including target organ damage and target organ complications • BP not optimally controlled -Poor compliance -On monotherapy -Not on right medication and right dose

Resistant Hypertension-Definition • Blood pressure remaining above goal in spite of concurrent use of 3 anti- hypertensive agents of different classes.

• Ideally, 1 of the 3 agents should be a diuretic and all agents should be prescribed at optimal dose .

• The BP goal is <140/90 mmHg in general, and <130/90 mmHg in hypertensive patients with diabetes or chronic kidney disease

Resistant Hypertension-Definition for diagnosing resistant hypertension â&#x20AC;˘ Use of diuretic is recommended but not required. â&#x20AC;˘ Doses should be optimal but not necessarily maximal.

Controlled Resistant Hypertension Patients who require 4 or more medications to control their BP are considered to have resistant hypertension

Pseudoresistance

(appearance lack of BP control) Causes • Inaccurate measurement of BP • Inappropriate drug choices/doses • Suboptimal treatment- frequently due to clinical inertia(provider’s failure to increase therapy when the treatment goal is not reached) • Nonadherence to prescribed therapy • White coat effect - mean daytime BP<135/85mmHG

Contributing Factors for RH  Volume expansion • Excess sodium intake • Volume retention secondary to CKD • Inadequate diuretic therapy  Obesity

Contributing Factors-Exogenous Substances • • • • • • • • •

Nonsteroidal anti-inflammatory agents/COX-2 Inhibitors Oral contraceptives Alcohol Corticosteroids/anabolic steroids Sympathomimetic agents-nasal decongestants Caffeine Cyclosporine Erythropoietin Antidepressants

Secondary Causes of RH Common • • • •

OSA Renal parenchymal diseases Hyperaldosteronism Renal Artery Stenosis

Uncommon • • • •

Pheochromocytoma Cushing’s disease Hyperparathyroidism Coarctation of aorta

Prevalence of RH â&#x20AC;˘ 5-30% of the overall hypertensive population have resistant hypertension Mancia G. J Hypertens 2007;25: 1105-87

â&#x20AC;˘ Only about 10% of patients have true resistant hypertension Mancia G. J. Hypertens 2007: 25:1105-87 Kaplan NM. J. Hypertens 2005 : 23 :1441-44

Prevalence of RH in Malaysia Prevalence of resistant Hypertension in a multiethnic cohort of hypertensive patients Y.Chia, J. of Hyper Vol 30,e-SupplementA, April 2012,e627

• 1,222 patients attending Primary Care Medicine at UMMC • Target BP : <140/90 mmHG : <130/80 mmHg for diabetic • Overall prevalence of resistant hypertension was 11% 8.1% without DM 13.3% with DM

Prevalence of white coat RH The prevalence of white-coat resistant hypertension(WC-RH) amongst patients referred for catheter based renal denervation(RDN) procedure for true resistant hypertension at National Heart Institute of Malaysia; R. Zambahari •37 patients were enrolled. Inclusion criteria for RDN are those used in Symplicity HPT 1&2 •WC-RH is defined as average daytime ABPM <135/85 •All patients had ABPM assessment •13(35%) had WC-RH and 24(65%) were classified as TRH •The use of ABPM may avoid mislabelling patient with TRH thus avoiding unnecessary tests to look for secondary HPT and expensive invasive procedures

Evaluation • • • •

Measurement technique.

Is patient compliant ?

Confirm appropriate treatment.

Obtain home, work or ambulatory B.P. to exclude white coat HTN. • Identify causes – secondary ?

• Look for co-morbid conditions.

• Document target organ damage.

Treatment of RH  Non pharmacologic therapies • Weight loss • Regular exercise • Low salt intake • Limit alcohol ingestion • Low fat / High fiber diet  Interfering subtances should be withdrawn or down titrated  Secondary causes should be treated

Pharmacologic Treatment of RH • Full doses of appropriate combination such as ACE I or ARB + CCB + Thiazides diuretics • Long acting thiazides(eg chlorthalidone)are effective.

• Consider adding mineralocorticoid receptor antagonist.

-Spironolactone -Eplerenone(more selective and better tolerated • Use of loop diuretic in CKD(Cr Cl < 30 ml/min)

Renal Nerve & Sympathetic Activity:

Kidney as Origin & Recipient of Central Sympathetic Drive

• Vasoconstriction • Atherosclerosis

Afferent Nerves

Efferent Nerves

Blood Pressure

↑ Renin Release  RAAS activation ↑ Sodium Retention ↓ Renal Blood Flow ↓ Kidney function

+ Increase co-morbidities

Schlaich et al. Hypertension. 2009;54(6):1195-1201.

• ↑ Contractility • ↑ Heart rate • Hypertrophy • Arrhythmia • Heart Failure

60

Symplicity HTN-2: RDN Superior to Medical Management, Reductions Sustained to 18M Primary Endpoint (6M post Randomisation) RDN (n=49)

∆ from Baseline to 6 Months (mmHg)

Control (n=51)

Systolic Diastolic Diastolic

Systolic

Latest Follow-up (18M post Randomisation)

p <0.0001 for ∆ between RDN and Control

RDN (n=43)

∆ from Baseline to 18 Months (mmHg)

Diastolic

Systolic p <0.01 for ∆ from baseline

Primary Endpoint: •>80% of RDN patients had ≥10 mmHg reduction in SBP •5 patients had ≤ 5mmHG reduction in SBP

Case 1 • • • •

JAR 57 year old Malay lady Hypertension : 1995 No secondary cause found Diabetes Mellitus : since 1995 Rt corona-radiata and internal capsule stroke early 2005 – fully recovered • IHD had PCI to LCx Dec 2005 • Hyperlipidaemia 2005 • BMI 32

Medication Dec 2010: • • • • • • • •

Amlodipine 10 mg o.d Metoprolol 100 mg b.d Perindopril 8 mg o.d Hydrochlorothiazide 25 mg o.d Simvastatin 40 mg o.d Metformin SR 850 mg b.d Diamicron 160 mg b.d Caspirin 100 mg o.d From 2006 to 2010 her BP range 120 -150 systolic 70 – 90 diastolic

• 30 March 2011 presented to ED with Heart Failure. BP was 190/95 mmHg. IV Frusemide 40mg was given. After 24 hrs BP normalised. She was discharged and continued on the same medication • 24 Nov 2011 BP= 200/98 mmHg, 192/93 mmHg after 10 min rest Spironolactone 25 mg was added 24 Hour Ambulatory BP was requested • 26 Jan 2012 BP= 190/95 pulse rate 76/min Prazosin 0.5 mg b.d was added

Ambulatory Blood Pressuring monitoring 18 Jan 2012

• Renal Function Test Electrolyte normal Serum Creatinine 99 umol/L (GFR 61.3ml/min)

• BP Medication: – – – – – –

Amlodipine 10 mg o.d Metoprolol 100 mg b.d Perindopril 8 mg o.d Hydrochlorothiazide 25 mg o.d Spironolactone 25mg o.d Prazosin 0.5mg b.d

Diagnosed as Resistant Hypertension

• What Next?

• Renal Artery Denervation

RT Renal Angiogram • Procedure begin at 16:15 • 6 Fr 55cm RDC GC • Selective renal angiogram taken using diluted contrast 1:1

RT Renal Artery Ablation

• Simplicity catheter inserted • 6 ablation given from distal to proximal

• Temp 55°C • 8 Watts for 120 seconds • 15% impedance drop

RT Renal Angiogram Pre & Post Ablation

• Pre Ablation

• Post Ablation

LT Renal Angiogram Pre & Post Ablation

• Pre Ablation

• Post Ablation • Procedure completed 17:15

• Medications given during procedure – – – – –

Heparin 7000 units, IA Fentanyl 0.3mL, IV Midazolan 1mL/h, IV Maxolan 10mg, IV Morphine 5mg, IV

• No post procedure complications • No change in medications • BP on the following day was 140/90 mmHg before discharge

BP and no. of medications pre and post RDN Pre RDN

Discharge 24/2/2012

19/04/2012

30/08/2012

1/11/2012

BP

190/95

140/90

184/84

120/80

160/80

No. of medications

• Amlodipine 10 mg od • Metoprolol 100 mg bd • Perindopril 8 mg od • HCT 25 mg od • Spironolac 25mg od • Prazosin 0.5mg bd

Se Creatinine

99 umol/L

• Prazocin 1mg b.d • Perindopril 8mg o.d • Amlodipine 10mg o.d • Spironolac 12.5mg o.d

123 umol/L

Case 2 • • • • • •

SCM (06821944) 50 yr old Malay man DM 20 years HPT for 20 years- Uncontrolled for the past one year End stage renal failure on HD for 8 years History of Lacunar stroke Medications: - Ibersartan 300mg od - Metoprolol 100mg bd - Methyldopa 250mg tds - Adalat SR 40mg bd - Physiotens 0.4mg od - Rocatriol, CaCo3 - Ticlid 250mg od

• On 25/4/2012 developed LVF due to uncontrolled HPT- BP 222/94mmHg • What next?

RDN using Ardian Catheter • • • • • • •

IV Fentanyl and IV Midazolam RFA approach 6F RDC Lt Renal artery 5sites Rt Renal artery 5 sites Uneventful procedure Discharged the following day with BP 150/80

BP and no. of medications pre and post RDN Pre RDN

Discharge 31/5/2012

25/06/2012

10/09/2012

05/11/2012

BP

192/84

150/80

204/98

122/58

130/70

No. of medications

• Ibersartan 300mg od • Metoprolol 100mg bd • Methyldopa 250mg tds • Adalat SR 40mg bd •Physiotens 0.4mg od

• Physiotens 0.4mg od • Metoprolol 50mg bd • Adalat SR 40mg od

Case 3 â&#x20AC;˘ Vagal Response during Renal Denervation - A prolonged response ?

• 73 year old Male • stable coronary artery disease ( last EST 2011 negative) • Hypertensive • Diabetic • Hyperlipidaemia

Medications : • Valsartan 80 mg o.d • Hydrochlorothiazide 25 mg o.d • Metoprolol 100 mg b.d • Amlodipine 10 mg o.d • Atovastatin 20 mg o.d • Metformin 500 mg t.d.s • Glicazide 80 mg b.d

Echocardiography • LVIDd : 5.0 cm • LVIDs : 3.3 cm • IVSd : 1.7 cm • LVEF : 60% • Trivial mitral and aortic regurgitation

Blood Pressure • Office BP : 165/97 • Average 24-hr BP : 154/90 • Average Day BP : 162/96 • Average Night BP : 138/81

Hemodynamics pre ablation

(L) Renal Angiogram pre ablation

First Ablation

Second Ablation

Status post ablation - Cath Report

Hemodynamics post 2nd ablation

Hemodynamics during procedure (Anaesthetistâ&#x20AC;&#x2122;s chart)

Vasopressin infusion given

BP monitoring during ablation

(L) Renal Angiogram pre ablation

(L) Renal Angiogram post 2 ablations

• Taken to CCU for monitoring • All anti hypertensives stopped • BP gradually pick up over 24 hours • Transferred well to the normal ward after 2 days CCU monitoring • Discharged home well with no antihypertensives • BP on discharge : 110/70 mmHg

Progress

Pre ablation

2 weeks post ablation

1 month post ablation

3 months post ablation

Office BP

165/97

120/80

156/83

160/85

Average 24hr BP

154/90

127/79

150/80

140/83

Average Day BP

162/96

134/84

160/87

146/86

Average Night BP

138/80

118/74

131/71

131/87

Anti HPT drugs

None

None

Norvasc 10 mg dly

Norvasc 10 mg dly Valsartan 160 mg dly

Case 4 • • • • •

Mr HBM 66 year old Malay man Stable Angina with 3 vessel disease for CABG HPT for 10 years. SBP always in 200 mmHg range.

Hyperlipidemia BMI 27

Medication : • Metoprolol 50 mg BD • Amlodipine 10 mg OD • Valsartan 160 mg OD • HCTZ 12.5 mg OD Renal function: Serum Creatinine 117 umol/L (GFR 60 mls / min)

Serial Office BP 16.1.2013

29.1.2013

4.2.2013

200/ 120

192/92

230/ 100

mmHg

No ABPM done RDN was offered for BP control prior to CABG

Hemodynamics before RDN

200

Hemodynamics During first ablation

160

Hemodynamics at the end of 2nd ablation

100

Hemodynamics post procedure after IV Atropine and IV Normal Saline

130

Next day review BP overnight 140/80 mmHg Medications: • Bisoprolol 5 mg OD • Amlodipine 10 mg OD

Future Development in the Horizon

New Drugs for Hypertension Several pharmacological targets have been discovered with promising pre-clinical results, however the clinical development of novel antihypertensive drugs have been more difficult and less productive than expected

Comprehensive SYMPLICITY Clinical Trial Program follows over 5000 patients across multiple indications First-in-Man First-in-Man(AU) (AU)

Symplicity HTN-1 Series SeriesofofPilot PilotStudies Studies (EU, US & AU) (EU, US & AU) Symplicity SymplicityHTN-2 HTN-2 Initial InitialRCT RCT (EU & AU) (EU & AU)

SYMPLICITY SYMPLICITYHTN-3 HTN-3 US USPivotal PivotalTrial Trial(US) (US)

Global GlobalSYMPLICITY SYMPLICITY Registry Registry (Approved (ApprovedRegions) Regions)

Expand ExpandHTN HTNIndication Indication (Approved (ApprovedRegions) Regions)

Trials under way

Pilot PilotStudies Studiesinin New NewIndications Indications (Approved (ApprovedRegions) Regions)

Conclusion • In Malaysia, the prevalence of HPT is high but levels of awareness, treatment and control are low.

• Successful treatment of hypertension is difficult despite the availability of several classes of antihypertensive drug and strategies to tackle the effect of adverse lifestyle behaviors on blood pressure • A substantial subset of patients exists in whom adequate control of blood pressure cannot be achieve despite prescribing and taking of several appropriate antihypertensive medication

Conclusion • Renal Denervation therapy(RDN) is a novel and exciting technology which offers an organ-specific strategy to decrease SNS activity and to manage HPT • Many centres are gaining experience and plenty more to be learn-more data will be presented/published • Appropriate patient selection is crucial for treatment success of RDN and emphasize the importance of F/U care and continued adherence to all antiHPT medication • Many new devices and procedures are in the pipeline, thus leading to a new era of outcome trials and evidence-based guidelines

This is not the end.

It is not even the beginning of the end.

But it is, perhaps the end of the beginning (Sir Winston S. Churchill)

-Thank You-

Original Entry Criteria

Reasons

1)

Renal artery ≥ 4mm in diameter and ≥ 20mm length

Large enough artery to deliver energy

2)

Age ≥ 18

Able to consent for study

3)

Systolic BP ≥ 160mmHG (average of 3 office reading)

Ensure consistency in the study population

4)

Adhering to 3+ anti-HTN drugs

Ensure consistency in the study population

5)

eGFR at ≥ 45

Extra careful in FIM and early clinical experience

Original Entry Criteria

Reasons

6)

Wanted to treat ideal anatomies

7)

No renal arterial abnormality – No significant renal artery stenosis – No prior renal artery intervention – No multiple renal arteries in either kidney No ACS or CVA within 6 months at screening No wide spread atherosclerosis

Not to confuse events due to underlying disease from events associated with renal denervation

8)

No heamodynamically significant valvular heart disease

Drops in BP in these patient may not be desirable

9)

No Type 1 DM

Long-standing Type 1 DM have much higher rates of CV complication and renal failure

10) No ICD or pacemaker

The devices may be adversely affected by RF ablation

11) Not pregnant, nursing

Radiation, contrast and procedure have not been studied in the setting of pregnancy