June 1, 2001
View Full PaperRationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial
Key Result
The ASCOT trial randomized 19,342 hypertensive patients to compare amlodipine-based versus atenolol-based regimens and atorvastatin versus placebo for the primary prevention of CHD.
Study Design
Type
RCT (n=19,342)
Blinding
Open, blinded endpoint; double-blind for factorial component
Randomization
2 x 2 factorial
Multicenter
Yes
Structured PICO
Does a newer antihypertensive regimen (amlodipine +/- perindopril) and/or atorvastatin reduce non-fatal MI and fatal CHD compared to an older regimen (atenolol +/- bendroflumethiazide) and/or placebo in hypertensive patients with multiple risk factors?
P
Population
19,342 men and women aged 40-79 with hypertension and at least three additional cardiovascular risk factors.
I
Intervention
Amlodipine (5/10 mg) +/- perindopril (4/8 mg) to reach blood pressure <=140/90 mmHg. Patients with total cholesterol <=6.5 mmol/l were further randomized to atorvastatin 10 mg daily.
C
Comparator
Atenolol (50/100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+. Patients in the lipid-lowering limb received matching placebo.
O
Outcome
Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD)composite
The ASCOT trial was designed to evaluate whether a newer antihypertensive regimen (amlodipine-based) and atorvastatin are superior to an older regimen (atenolol-based) and placebo in preventing CHD in hypertensive patients with multiple risk factors.
Abstract
OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.