Beta-blockers against other antihypertensive drugs

Beta-blocker (mostly atenolol) treatment for primary hypertension is associated with a higher risk of stroke than treatment with other antihypertensive agents. Compared with placebo, beta-blockers reduce the risk of stroke by 19%, which is about half that expected from previous hypertension trials.

A systematic review including 13 studies with a total of 105951 subjects was abstracted in DARE. The trials compared beta-blockers with other antihypertensive drugs. Of these patients, 56301 were in atenol trials, 33971 in mixed trials with atenolol and diuretics, and only 9004 in non-atenolol trials. Seven studies with a total of 27433 subjects were included in a comparison of beta-blockers and placebo or no treatment. The relative risk of stroke was 16% higher for beta-blockers than for other drugs (95% CI 4 to 30%). When the effect of beta-blockers was compared with placebo or no treatment, the risk of stroke was reduced by 19% for all beta-blockers (95% CI 7 to 29%). There was no difference for myocardial infarction or mortality.

A multicentre, prospective, randomised controlled trial 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.

The following decision support rules contain links to this evidence summary:

• Replacing atenolol with other antihypertensives
• Antihypertensives other than beta-blockers as monotherapy after TIA or stroke

Ədəbiyyat

1. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005 Oct 29-Nov 4;366(9496):1545-53.
2. 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.