How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis

Objective To quantify the effect of first-line antihypertensive treatment with beta-blockers on mortality, morbidity and withdrawal rates, compared with the other main classes of antihypertensive agents. Methods We identified eligible trials by searching the Cochrane Controlled Trials Register, Medline, Embase, reference lists of previous reviews, and contacting researchers. We extracted data independently in duplicate and conducted meta-analysis by analysing trial participants in groups to which they were randomized, regardless of subsequent treatment actually received. Results Thirteen trials with 91 561 participants, meeting inclusion criteria, compared beta-blockers to placebo (four trials; n = 23 613), diuretics (five trials; n = 18 241), calcium-channel blockers (CCBs) (four trials; n = 44 825), and renin–angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (three trials; n = 10 828). Compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% confidence interval 0.66–0.96) with a marginal fall in total cardiovascular events (0.88, 0.79–0.97), but did not affect all-cause mortality (0.99, 0.88–1.11), coronary heart disease (0.93, 0.81–1.07) or cardiovascular mortality (0.93, 0.80–1.09). The effect on stroke was less than that of CCBs (1.24, 1.11–1.40) and RAS inhibitors (1.30, 1.11–1.53), and that on total cardiovascular events less than that of CCBs (1.18, 1.08–1.29). In addition, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33–2.42) or RAS inhibitors (1.41; 1.29–1.54). Conclusion Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. Compared with diuretics, they had similar outcomes, but were less well tolerated. Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.

[1]  P. Tanuseputro.  Should B Blockers Remain First Choice in the Treatment of Primary Hypertension? A Meta-Analysis , 2006 .

[2]  G. Mancia,et al.  New-onset diabetes and antihypertensive drugs. , 2006, Journal of hypertension.

[3]  Alice Stanton,et al.  Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study , 2006, Circulation.

[4]  L. Lindholm,et al.  Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis , 2005, The Lancet.

[5]  B. Williams,et al.  The diabetogenic potential of thiazide-type diuretic and beta-blocker combinations in patients with hypertension , 2005, Journal of hypertension.

[6]  R. Collins,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 tri , 2005, The Lancet.

[7]  J. Staessen,et al.  Angiotensin-Converting Enzyme Inhibitors and Calcium Channel Blockers for Coronary Heart Disease and Stroke Prevention , 2005, Hypertension.

[8]  A. Zanchetti.  Evidence-based medicine in hypertension: what type of evidence? , 2005, Journal of hypertension.

[9]  Rachel Leach,et al.  Rethinking the “Diseases of Affluence” Paradigm: Global Patterns of Nutritional Risks in Relation to Economic Development , 2005, PLoS medicine.

[10]  K. Reynolds,et al.  Global burden of hypertension: analysis of worldwide data , 2005, The Lancet.

[11]  L. Lindholm,et al.  Atenolol in hypertension: is it a wise choice? , 2004, The Lancet.

[12]  J. Staessen,et al.  Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects. , 2004, American journal of hypertension.

[13]  R. Schall,et al.  Old antihypertensives and new diabetes , 2004, Journal of hypertension.

[14]  G. Reboldi,et al.  Adverse Prognostic Significance of New Diabetes in Treated Hypertensive Subjects , 2004, Hypertension.

[15]  Carl J Pepine,et al.  A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. , 2003, JAMA.

[16]  T. Pickering,et al.  beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension. , 2003, American journal of hypertension.

[17]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[18]  L. Dobrucki,et al.  Third-Generation &bgr;-Blockers Stimulate Nitric Oxide Release From Endothelial Cells Through ATP Efflux: A Novel Mechanism for Antihypertensive Action , 2003, Circulation.

[19]  J. Staessen,et al.  Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003 , 2003, Journal of hypertension.

[20]  Peter Sleight,et al.  Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. , 2003, JAMA.

[21]  Tom Greene,et al.  Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. , 2002, JAMA.

[22]  G. Mancia,et al.  Calcium Antagonist Lacidipine Slows Down Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of the European Lacidipine Study on Atherosclerosis (ELSA), a Randomized, Double-Blind, Long-Term Trial , 2002, Circulation.

[23]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[24]  M. Nieminen,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[25]  R. Schall,et al.  Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy. , 2002, Journal of the American College of Cardiology.

[26]  Jan A Staessen,et al.  Cardiovascular protection and blood pressure reduction: a meta-analysis , 2001, The Lancet.

[27]  P. Doevendans,et al.  Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide production. , 2000, Circulation.

[28]  Thomas Hedner,et al.  Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study , 2000, The Lancet.

[29]  I. Olkin,et al.  Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement , 1999, The Lancet.

[30]  T. Hedner,et al.  Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study , 1999, The Lancet.

[31]  L. Poston,et al.  British Hypertension Society guidelines for hypertension management 1999: summary , 1999, BMJ.

[32]  L. Niskanen,et al.  Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial , 1999, The Lancet.

[33]  Philip D. Harvey,et al.  Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39 , 1998, BMJ.

[34]  L. Opie.  Evidence is needed that ß blockade alone reduces mortality in hypertension , 1997, BMJ.

[35]  S. Wellek,et al.  Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study , 1997, BMJ.

[36]  M. Brown.  Science, medicine, and the future : Hypertension , 1997, BMJ.

[37]  B. Psaty,et al.  Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. , 1997, JAMA.

[38]  Roberto Sega,et al.  Blood-pressure control in the hypertensive population , 1997, The Lancet.

[39]  Detection.  The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) , 1997 .

[40]  R. Weinshilboum,et al.  The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. , 1997, Archives of internal medicine.

[41]  C. Dollery,et al.  Medical Research Council trial of treatment of hypertension in older adults: principal results. , 1992 .

[42]  B. Dahlöf,et al.  Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) , 1991, The Lancet.

[43]  R. Collins,et al.  Blood pressure, stroke, and coronary heart disease Part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context , 1990, The Lancet.

[44]  R. Collins,et al.  Blood pressure, stroke, and coronary heart disease Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias , 1990, The Lancet.

[45]  J. Tuomilehto,et al.  Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study. , 1988, JAMA.

[46]  J. Tuomilehto,et al.  Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. , 1987, Journal of hypertension.

[47]  O. Andersson,et al.  Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide. , 2009, Acta medica Scandinavica.

[48]  T S Warrender,et al.  Randomised trial of treatment of hypertension in elderly patients in primary care. , 1986, British medical journal.

[49]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[50]  W. Haenszel,et al.  Statistical aspects of the analysis of data from retrospective studies of disease. , 1959, Journal of the National Cancer Institute.