Amlodipine adding perindopril versus atenolol adding bendroflumethiazide for hypertension
Evidence Summaries Level of Evidence = A
An amlodipine-based regimen adding perindopril prevented more major cardiovascular events and induced less diabetes than an atenolol-based regimen adding bendroflumethiazide, although the result was not significant for the primary endpoint (non-fatal myocardial infarction and fatal coronary heart disease (CHD)).
A multicentre, prospective, randomised controlled trial 1 was performed in 19,257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). The primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106,153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). Comment: There was a 2.7 mmHg systolic blood-pressure difference favouring the amlodipine-perindopril group which explains part of the difference in outcomes.
1. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, ASCOT Investigators. 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 Sep 10-16;366(9489):895-906. [PMID:16154016]
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