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Evidence summaries

Beta-Blockers Against other Antihypertensive Drugs

Beta-blocker (mostly atenolol) treatment for primary hypertension appears to be associated with a higher risk of stroke than treatment with other antihypertensive agents. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment).

Summary

A Cochrane review [Abstract] 1 included 13 studies with a total of 91 561 subjects (beta-blockers vs. placebo or no treatment 4 trials, n=23 613; vs. diuretics 5 trials, n=18 241; vs. calcium-channel blockers 4 trials, n=44 825 participants; vs. renin-angiotensin system inhibitors 3 trials, n=10 828). Most of the evidence comes from trials with atenolol as the beta-blocker used (75% of beta-blocker participants). No studies involving newer vasodilating beta-blockers (e.g. nebivolol) were found.

The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11; 4 studies, n=23 613), diuretics or renin-angiotensin system (RAS) inhibitors, but was higher for beta-blockers compared to calcium-channel blockers (CCBs; RR 1.07, 95% CI 1.00 to 1.14; 4 studies, n=44 825, NNTH=200 for 5 years). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; 4 studies, n=23 613, NNTB=140 for 5 years). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; 4 studies, n=23 613, NNTB=200 for 5 years); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo.

The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; 2 studies, n=19 915, NNTH=80), but was not significantly different from that of diuretics or RAS inhibitors. In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; 3 studies, n=44 167, NNTH=180) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; 2 studies, n=9 951, NNTH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In the single study involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32).

Patients on beta-blockers were more likely to discontinue treatment due to side effects than those on RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; 2 studies, n=9 951, NNTH=18), but there was no significant difference with placebo, diuretics or CCBs.

A systematic review 2 included 13 studies with a total of 105951 subjects. 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 3 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.

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    References

    • Wiysonge CS, Bradley HA, Volmink J et al. Beta-blockers for hypertension. Cochrane Database Syst Rev 2017;(1):CD002003. [PubMed]
    • Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005;366(9496):1545-53. [PubMed]
    • 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;366(9489):895-906. [PubMed]

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