Htn for nhf conference presentation1

Dhaka 2012

SBP = 100 + your ageThis may be usual but is not normal

BP>160/90

BP>140/90

These are BP levels to treat

Dhaka 2012

Hypertension SBP > 140Borderline Hypertension SBP 130-140Non Optimal BP SBP >115Normal BP < 115/75

In the young DBP may be as or even more important

Between Hypertension and Optimal BP.

50% of Events

Kaplan et.al, Lancet 2006

Dhaka 2012

ESH-ESC Guidelines 2007

Kaplan et.al, Lancet 2006

0 5 10 15 20

Percentage of Mortality Attributable to Risk Factors

*Based on The World Health Report 2003 Yach et al. JAMA. 2004;291:2616-2622.

Developing countries

Developed countries

Blood pressure

Tobacco

Underweight

Alcohol

Cholesterol

Unsafe sex

OverweightUnsafe water, sanitation,

hygieneLow fruit and vegetable intake

Indoor smoke from solid fuels

Physical inactivity

Thank You

JNC 7 ESH–ESC WHO–ISH BHS/NICE 2006

Thiazide-type

diuretics

Any of 5

(A,A,B,C,D)

Low-dose

diuretics

A/CD

2-drug

combination

2-drug

combination– –

Compelling

indication for

others

Compelling

indication for

others

Compelling

indication for

others

Compelling

indication for

others

“Monotherapy is

usually inadequate

therapy”

BHS IV

The available evidence does not support the use of

beta-blockers as first-line drugs in the treatment of

hypertension. This conclusion is based on the relatively

weak effect of beta-blockers to reduce stroke and the

absence of an effect on coronary heart disease when

compared to placebo or no treatment. More importantly,

it is based on the trend towards worse outcomes in

comparison with calcium-channel blockers, renin-

angiotensin system inhibitors, and thiazide(?) diuretics.

Wiysonge et al. Cochrane Database Sys Rev 2007;1:CD002003

Lifestyle modifications

Chobanian AV et al. JAMA. 2003;289:2560–2572.

Not at goal BP*

Hypertension without compelling indications

Hypertension with compelling indications

Stage 1

Thiazide-type diuretics for most. May consider ACE inhibitor, ARB, β-blocker,

CCB, or combination

Stage 2

Two-drug combination for most (usually including thiazide-type diuretic)

If not at goal, optimize dosages or add additional drugs until goal BP is achieved.

Consider consultation with hypertension specialist

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACE

inhibitor, ARB, β-blocker, CCB) as needed

*BP goal <140/90 mmHg or <130/80 mmHg for those with diabetes or chronic kidney disease

ESH-ESC Guidelines 2007 Treatment algorithms

Marked BP elevation High/very high CV risk Lower BP target

Two-drug combination at low dose

Mild BP elevationLow/moderate CV riskConventional BP target

Choose between

Single agentat low dose

Previous agentat full dose

Switch to different agentat low dose

Two-to three-drugcombination at full dose

Full dosemonotherapy

If goal BP not achieved

If goal BP not achieved

Two-to three-drugcombination at full dose

Monotherapy versus combination therapy strategies

Previous combinatonat full dose

Add a third doseat low dose

J Hypertens. 2007;25:1105–1187.

• ACE inhibitor plus Diuretic

• ARB plus Diuretic

• CCB plus Diuretic

• ACE inhibitor plus CCB

• ARB plus CCB

= “A+D”

= “A+C”

A + D ?

TRIAL VS

LIFE - B + D

VALUE - C + D

PROGRESS - Placebo

HYVET - Placebo

ADVANCE - Placebo

A + C ?

Thiazide diuretics

ACE inhibitors

Calcium antagonists

ß-blockers AT1-receptor antagonists

α-blockers

2007 ESH/ESC Guidelines

Combination between some classes ofantihypertensive drugs

J Hypertens. 2007;25:1105-1187.

ASCOT-BPLA

www.ascotstudy.org

atenolol ±bendroflumethiazide

amlodipine ±perindopril

19,342 hypertensive

patients

PROBE design

ASCOT-BPLA

placeboatorvastatin 10 mg Double-blind

ASCOT-LLA10,305 patients

TC ≤ 6.5 mmol/L (250 mg/dL)

Investigator-led, multinational randomised controlled trial

ASCOT-BPLA: summary of all end points

Dahlöf B, et al. Lancet. 2005;366:895-906.

amlodipine/perindopril better atenolol/thiazide better

0.50 0.70 1.00 1.45

PrimaryNon-fatal MI (incl silent) + fatal CHD

SecondaryNon-fatal MI (exc. Silent) +fatal CHDTotal coronary end pointTotal CV event and proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure

TertiarySilent MIUnstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment

Post hocPrimary end point + coronary revasc procsCV death + MI + stroke

2.00

Unadjusted HR (95% CI)

0.90 (0.79-1.02)

0.87 (0.76-1.00)0.87 (0.79-0.96)0.84 (0.78-0.90)0.89 (0.81-0.99)0.76 (0.65-0.90)0.77 (0.66-0.89)0.84 (0.66-1.05)

1.27 (0.80-2.00)0.68 (0.51-0.92)0.98 (0.81-1.19)0.65 (0.52-0.81)1.07 (0.62-1.85)0.70 (0.63-.078)0.85 (0.75-0.97)

0.86 (0.77-0.96)0.84 (0.76-0.92)

BHS/NICE Proposal : 2011Antihypertensive drug treatment

No evidence for benefit of truly low-dose thiazides vs. placebo

Low-dose thiazides vs. anything was inferior (ANBP2, ASCOT, ACCOMPLISH)

Good evidence of CV benefits for

a) higher dose Thiazides (+/- K+ sparing)

b) Chlorthalidone

c) Indapamide

SBP

mmHg

DBP

mmHg

Doxazosin* 11.7 6.9

Spironolactone† 21.9 9.5

*Chapman et al. Circulation 2008†Chapman et al. Hypertens 2007

WHAT NOT TO COMBINE!

Ramipril Telmisartan Combination

Systolic -6.0 -6.9 -8.4

Diastolic -4.6 -5.2 -6.0

ON TARGET

Change in BP (mmHg)

* Death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.

ON-TARGET Trial:(27) Kaplan-Meier Curves for the Primary Outcome*

Study ID

Schweizer et al. 2007

Taylor et al. 2003

Asplund et al. 1984

Gerbino et al. 2004

Dickson et al. 2008

I-V Overall (I-squared = 0.0%, p = 0.655)

D+L Overall

1.08 (0.75, 1.54)

1.09 (0.80, 1.51)

1.74 (0.96, 3.15)

1.28 (0.93, 1.75)

1.29 (0.89, 1.89)

1.21 (1.03, 1.43)

1.21 (1.03, 1.43)

0.5 1.0 1.5 2.0

Favours FDCFavours free dose combination

N=18,004

OR (95% CI)

Odds RatioGupta : Hypertension : 2010

Drug choice: summary and generic issues (BHS IV)

1. Overall benefits of BP lowering derive from BP level achieved although

2. Possible class-specific benefits include:

- CCB’s less protective vs heart failure?

- CCB’s and ARB’s more protective vs stroke?

- Compelling indications for specific conditions?

4. Use once daily agents (full 24 hour effect)

5. Allow 4 weeks to evaluate

6. Titrate to manufacturer’s instructions (except Di)

7. When all else equal, use the least expensive drug

8. If no cost disadvantage – encourage fixed-dose combinations

BHS IV: Other medications for hypertensive patients

Primary prevention

(1) Aspirin: use 75mg daily if patient is aged 50 years with blood pressure controlled to <150/90 mm Hg and either; target organ damage, diabetes mellitus, or 10 year risk of cardiovascular disease of 20% (measured by using the new Joint British Societies’ cardiovascular disease risk chart)

(2) Statin: use sufficient doses to reach targets if patient is aged up to at least 80 years, with a 10 year risk of cardiovascular disease of

20% (measured by using the new Joint British Societies’ cardiovascular disease risk chart) and with total cholesterol concentration 3.5mmol/l

(3) Vitamins—no benefit shown, do not prescribe