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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