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Anglo-Scandinavian Cardiac Outcomes Trial: Blood Pressure-Lowering Arm - ASCOT-BPLA
Contribution To Literature:
The ASCOT trial revealed the benefit of amlodipine/perindopril for blood pressure control.
Description:
The goal of the blood pressure lowering arm of the trial was to evaluate whether treatment with a newer antihypertensive regimen of calcium channel blocker with or without an angiotensin-converting enzyme (ACE) inhibitor is more effective than an older regimen of beta-blocker with or without a diuretic, and whether it reduces coronary heart disease (CHD) events in hypertensive patients with relatively low cholesterol levels.
Study Design
Patients Enrolled: 19,257
Mean Follow Up: 5.4 years
Mean Patient Age: Mean age 63 years
Female: 23
Patient Populations:
Systolic blood pressure (SBP) ≥160 mm Hg and/or diastolic blood pressure (DBP) ≥100 mm Hg (untreated) or SBP ≥140 mm Hg and/or DBP ≥90 mm Hg (treated); total cholesterol ≤6.5 mmol/l (250 mg/dl) and triglycerides ≤4.5 mmol/l (400 mg/dl); age 40-79 years; ≥3 cardiovascular disease risk factors; and no history of CHD
Exclusions:
Previous MI, currently treated angina, cerebrovascular event within three months, fasting triglycerides >4.5 mmol/l, heart failure, uncontrolled arrhythmias, or any clinically important hematological or biochemical abnormality on routine screening
Primary Endpoints:
Nonfatal MI and fatal CHD
Drug/Procedures Used:
Patients in the ASCOT trial were randomized open-label to one of the two antihypertensive treatments: amlodipine 5 mg (n=9,639) or atenolol 50 mg (n=9,618). In order to achieve target blood pressure goals of <140/90 mm Hg, study drug doses were increased and second-line drugs were added (perindopril 4 mg for the amlodipine group and bendroflumethiazide 1.25 mg for the atenolol group) as necessary.
Principal Findings:
At the end of the 2005 study, systolic blood pressure was slightly lower in the amlodipine/perindopril group (135.5 mm Hg vs. 136.3 mm Hg). Randomized therapy medication use was 73% atenolol, 67% bendroflumethiazide, 78% amlodipine, and 63% perindopril.
The trial was discontinued early due to a Data Safety and Monitoring Board recommendation, due to efficacy in the amlodipine/perindopril group and concerns regarding the patients in the atenolol/bendroflumethiazide group. The reduction in the primary endpoint of nonfatal myocardial infarction (MI) and fatal CHD was lower, although not significantly so in the amlodipine/perindopril group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.78-1.03, p = 0.12). However, several prespecified secondary endpoints were significantly lower in the amlodipine/perindopril group, including all-cause mortality (HR 0.86, 95% CI 0.78-0.96, p = 0.005), all coronary events (HR 0.86, p = 0.0048), all cardiovascular events and procedures (HR 0.84, p < 0.0001), stroke (HR 0.77, p = 0.0007), and cardiovascular mortality (HR 0.76, p = 0.0017).
At 16 years of follow-up: Incidence rate of all-cause mortality was 2.95 per 100 person-years in the amlodipine-based group vs. 2.99 per 100 person-years in the atenolol-based group (p = 0.34). Incidence rate of stroke was 0.13 per 100 person-years in the amlodipine-based group vs. 0.18 per 100 person-years in the atenolol-based group (p = 0.03).
New-onset diabetes was lower in the amlodipine/perindopril group compared with the atenolol/bendroflumethiazide group (HR 0.68, p < 0.0001). Prespecified subgroups showed similar efficacy. There were no differences in serious adverse events by treatment strategy.
Baseline CRP only minimally added to risk prediction and it did not indicate the magnitude of response to atorvastatin therapy.
Interpretation:
Among patients with hypertension and relatively low cholesterol, a strategy of treatment with amlodipine and perindopril if needed was associated with reductions in many secondary endpoints, including mortality, compared with treatment with the beta-blocker atenolol and the diuretic bendroflumethiazide, prompting the trial to be discontinued early in order to substitute appropriate alternative antihypertensive therapy in the beta-blocker group. At 16 years of follow-up, the amlodipine-based group was associated with a small, but significantly significant reduction in stroke.
The ALLHAT trial had a similar design, with hypertensive patients randomized to antihypertensive therapy, and a subgroup of patients with mild hypercholesterolemia randomized to pravastatin versus usual care. In ALLHAT, the risk of the prespecified primary endpoint of fatal CHD or nonfatal MI did not differ between initial use of the diuretic chlorthalidone versus initial use of the ACE inhibitor lisinopril or the calcium antagonist amlodipine. However, for certain secondary outcomes, such as chronic heart failure, rates were lower among patients treated with chlorthalidone versus lisinopril or amlodipine. While systolic blood pressure was slightly reduced in the amlodipine/perindopril strategy, it is unlikely that this small difference accounts for the entire clinical benefit.
There is little role for CRP in predicting risk or in making clinical decisions regarding statin therapy.
References:
Gupta A, Mackay J, Whitehouse A, et al. Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomized factorial trial. Lancet 2018;Aug 26:[Epub ahead of print].
Presented by Dr. Ajay Gupta at the European Society of Cardiology Congress, Munich, Germany, August 26, 2018.
Presented by Dr. Peter Sever at the American Heart Association Scientific Sessions, Chicago, IL, November 17, 2010.
Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906.
Presented by Dr. Peter S. Sever at the March 2005 ACC Annual Scientific Session, Orlando, FL.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Statins, Acute Heart Failure, Hypertension
Keywords: Perindopril, Bendroflumethiazide, Coronary Disease, Blood Pressure, Primary Prevention, Calcium Channel Blockers, Cholesterol, Hypertension, Myocardial Infarction, Stroke, Chlorthalidone, Diuretics, Heptanoic Acids, Hypercholesterolemia, Pyrroles, Lisinopril, Drug Combinations, Heart Failure, Pravastatin, Amlodipine, Triglycerides, Diabetes Mellitus
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