01. Smetana Hypertension Vietnam Sept. 2012

• JNC-7 guidelines • Use diuretics as first line Rx for most patients • Conflicting data on ARB’s • Risks of alpha-blockers • Reevaluation of beta-blockers • Costs of commonly used medic

Hypertension 2012:

Recent Evidence that Will

Change Your Practice

Gerald W Smetana, M.D.

Associate Professor of Medicine

Harvard Medical School

General medicine update:

Common health problems in primary care practice

Ho Chi Minh City and Hanoi, Vietnam

September 2012

• JNC-7 guidelines

• Use diuretics as first line Rx for most patients

• Conflicting data on ARB’s

• Risks of alpha-blockers

• Reevaluation of beta-blockers

• Costs of commonly used medications

• Resistant hypertension

• Expanding role for spironolactone

• Treatment in the elderly

All Drugs that Lower Blood

Pressure Do Not Equally Reduce

Cardiovascular Risk

Hypertension Rates Correlate with

Affluence: Rise in Affluence of Vietnamese

may Increase Hypertension Rates

Why Is This Important?

One Third of all Non- Infectious Deaths in Vietnam Due to Cardiovascular Disease

Hoang Van Minh, et al Prev Chronic Dis 2006;3:A89

Twice as Many CV

Deaths as Cancer

Deaths

What’s New?

• Lower target bp in diabetics does not further reduce CV events

• J Shaped curve reemerges

• ARBs do not reduce CV risk in high risk

patients

• Chlorthalidone preferred over HCTZ

• Spironolactone effective in resistant

hypertension

49.1 37.5

23.2

18.3

83.8

6.4 0.0

Distribution of Systolic Blood Pressure

Values Among Vietnamese Adults

J Human Hypert 2012:26:268

Relative Risk of CAD and Stroke

by Diastolic Blood Pressure

10 year follow up in 9 studies of untreated patients

Lancet 1990:335:765

3.5 x

2.0 x

Secondary (Identifiable) Causes

• Chronic renal disease

• Coarctation of the aorta

• Thyroid or parathyroid disease

• Obstructive sleep apnea

White Coat Hypertension:

A Pre-Hypertensive State

• 1412 patients followed for 10 years

• White coat HTN definition

– > 140/90 in office

– 24 hour monitoring < 125/79

– OR home casual reads < 132/83

• At study entry:

– 16% of patients had white coat hypertension

• At 10 years, rates of true sustained hypertension

– White coat hypertensives: 43%

– Normotensives: 18%

Hypertension 2009;54:226

What is Optimal Target BP? No Benefit from

Lower Target BP in Diabetic Patients

NEJM 2010;362:1575

N= 4733 Target sbp

120 vs 140

American Heart Association Statement:

Proven Lifestyle Modifications

DASH type diet Diet rich in fruits and

vegetables, low fat dairy

Obesity Trends Among U.S Adults

2009 1990

No Data <10% 10%–14% 15%–19% 20%–24% 2 25%–29% ≥30%

Data from U.S CDC

Obesity Rates in Vietnam are Much Lower

Than In the United States

would yield to dieting or to simple home

remedies, the doctor’s visit is not thought to be complete without the prescription.”

William Osler 1895

Hypertension Awareness and Treatment in Vietnam:

Only One Half Are Aware of Diagnosis

Son JT, et al

J Hum Hypert

2012

25 % Prevalence

49%

Aware

61%

Aware

Mr Nguyen

• Your patient, Mr Nguyen has had 3 office bp readings > 140/90 despite weight loss and regular exercise You feel medications are indicated You recommend:

1.Hydrochlorothiazide

2.Lisinopril

3.Valsartan

4.Chlorthalidone

All Drugs that Lower Blood Pressure Do Not

Equally Reduce CV Risk

• All commonly used first line

medications reduce bp to similar

extent

• Evidence from RCT’s

demonstrates varied reduction in

CV risk

• Diuretics as first line agent for

most patients unless compelling

TRANSCEND: Telmisartan Does Not Reduce

CV Endpoints if Intolerant to ACEi

NAVIGATOR: Valsartan Does Not Reduce CV Risk For Patients with Glucose Intolerance

ACEi + ARB More is Not Always Better:

No Difference in Composite CV Endpoint

Combination Therapy: More Adverse Events Despite No Additional CV Risk Reduction

Hypotensive Sx Syncope Renal Impairment

Ramipril Telmisartan Both

Aliskiren Increases Morbidity in Diabetic Patients with Renal Disease

• Direct renin inhibitor

• ALTITUDE Trial: Type 2 diabetes plus renal

impairment (proteinuria or CKD)

• All patients on ACEi or ARB

• Randomized to addition of aliskiren or placebo

• Composite outcome of mortality, CV, and renal

outcome

• Terminated due to lack of efficacy at 27 months

• Higher rates or renal impairment, hypotension, and hyperkalemia with aliskiren

• Marginal increase in stroke and death

• FDA: Contraindicated as part of dual Rx with ACEi

or ARB

Renin/Aldosterone Suppression:

Conclusions

• ACEi reduce CV risk to same degree as

diuretics

• ACEi are appropriate first-line agents

• ARB’s are not effective when ACEi intolerant

• ARB’s do not reduce CV events after stroke*

• Pending further study, would move ARBs to

second line status (controversial)

• Do not use aliskiren pending further study

* NEJM 2008;359:1225

Drug Selection in Specific Populations

• African-Americans

– More salt and volume sensitive

– Diuretics are drugs of first choice

unless contraindication

– Calcium channel blockers also

effective

– Beta-blockers, ACEi, and ARBs are

less effective than in whites

• Elderly patients

– Diuretics are preferred

– Long acting calcium blockers or ACEi

are second choice

Amlodipine Chlorthalidone Doxazosin

Pravastatin Usual care

Follow for CHD until death or end of study (mean 4.9 years)

Meta-Analysis: Diuretics Reduce CHF

to the Greatest Extent

Which Diuretic to Choose?

• JNC-7: Use diuretics as first line therapy unless compelling indication for other agent

• Chlorthalidone is twice as potent as HCTZ

• Longer half life than HCTZ of 24 hours

• More effective at lowering night time bp

• Most positive diuretic trials have used

chlorthalidone

preferred diuretic for Rx of hypertension

• Increased hypokalemia Medical Letter Feb 2009

ASCOT: Lower CV Event Rates

Onset DM Amlodipine Atenolol

14 Days Day 1 Month 1 Month 2 Year 5

Screening

Amlodipine 5 mg + benazepril 20 mg

Benazepril 40 mg + HCTZ 12.5 mg

Benazepril 40 mg + HCTZ 25 mg

Free add-on antihypertensive agents*

Month 3

Free add-on antihypertensive agents*

Amlodipine 5 mg + benazepril 40 mg

Amlodipine 10 + benazepril 40 mg

Benazepril 20 mg + HCTZ 12.5 mg

NEJM 2008;359:2417

ACCOMPLISH Trial:

ACEi/CCB vs ACEi/HCTZ

Calcium Channel Blockers: Recommendations

• Some conflicting data

• ASCOT benefits may be due to

inferiority of atenolol

• Higher CHF rates in ALLHAT

• ACCOMPLISH strongest data yet

• May be superior as part of

12,990 7,382

9,443 5,285

4,827 2,654

2,010 1,083

Rel Risk 1.25

p < 0.0001

95% CI 1.17-1.33

ALLHAT

JAMA 2000;283:1967

Flurry of Reports: Are Beta-Blockers

Effective for the Treatment of Hypertension?

• Updated Meta-Analysis of 13 trials

– Cochrane Database of Systematic Reviews

2009, Issue 1

Total Mortality: Beta-Blockers No More

Effective than Placebo

RR = 0.99

Coronary Artery Disease Events: Blockers No More Effective than Placebo

Beta-RR = 0.93

Beta-Blockers Modestly Reduce

Stroke Rates

RR = 0.80

Beta-Blockers: Recommendations

• Other trials have shown greater HR

reduction confers increased events*

• Do not use as first line or second line

treatment for hypertension

• Consider if three or more drugs required as

part of multi-drug regimen for patients with

drug intolerances and limited options

• Probably a class effect but most negative

trials are for atenolol

* JACC 2008;52:1482

Cochrane Review: Efficacy of 1 st Line

Treatments for Hypertension

Cochrane Library 2009, Issue 3

Significant Benefits: Only Thiazides and

ACEi Reduce All CV Endpoints

Cochrane Library 2009, Issue 3

Causes of Resistant Hypertension

(Uncontrolled despite 3 drugs including diuretic)

• Alcohol

• Severe essential HTN

One Third of Patients with Resistant

Hypertension Have White Coat Hypertension

Hypertension 2011;57:898

Spironolactone Effective for Many Patients with Resistant Hypertension

Summary of Evidence

reduction

Compelling indications

Post MI

Diabetes

LV dysfunction

Renin inhibitor Inferior if diabetes +

CKD

None

My Recommendations

First Line:

Diuretics ACEi CCB

Second Line:

ARB

Third Line: Labetalol Spironolactone Minoxidil

No Role:

Alpha blockers

Limited Role Multiple intolerances:

Beta blockers

• Lifestyle modification for all patients

• Diuretics as 1st line Rx unless

contraindication or compelling indication for other medication

• ACEi or CCB alternative 1st line options

• ARBs are probably inferior

• Beta-blockers and alpha blockers are inferior to other agents

• African-American and elderly patients are more responsive to diuretics

• Consider white coat HTN if resistant bp

• Spironolactone and labetalol for

resistant hypertension

All Drugs that Lower Blood

Pressure Do Not Equally Reduce

Cardiovascular Risk