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Evidence summaries

Different Antihypertensive Agents as First Line Therapies

Hypertension treatment with ACE-inhibitors, angiotensin-receptor blockers, beta blockers, calcium channel blockers, or low dose diuretics decreases cardiovascular events. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 24 studies with a total of 58 040 subjects. Low-dose thiazides reduced mortality (RR 0.89, 95% CI 0.82 to 0.97; 8 studies, n=19 874), stroke (RR 0.68, 95% CI 0.60 to 0.77; 8 studies, n=19 874), coronary heart disease (CHD) (RR 0.72, 95% CI 0.61 to 0.84; 7 studies, n=19 022) and total cardiovascular events (CVS) (RR 0.70, 95% CI 0.64 to 0.76; 7 studies, n=19 022). High-dose thiazides (11 studies, n=19 839) reduced stroke and total CVS, but did not reduce mortality, or CHD. Beta-blockers (5 studies, n=19 313) reduced stroke (RR 0.83, 95% CI 0.72 to 0.97) and CVS (RR 0.89, 95% CI 0.81 to 0.98) but not CHD (RR 0.90, 95% CI 0.78 to 1.03) or mortality (RR 0.96, 95% CI 0.86 to 1.07). In 4 of the 5 beta-blocker trials atenolol was the beta-blocker used. Thus, it is possible that the lesser effectiveness of first-line beta blockers is limited to atenolol. ACE inhibitors (3 studies, n=6 002) reduced mortality (RR 0.83, 95% CI 0.72 to 0.95), stroke (RR 0.65, 95% CI 0.52 to 0.82), CHD (RR 0.81, 95% CI 0.70 to 0.94) and CVS (RR 0.76, 95% CI 0.67 to 0.85). Calcium-channel blocker (1 study, n=4 695) reduced stroke (RR 0.58, 95% CI 0.41 to 0.84) and CVS (RR 0.71, 95% CI 0.57 to 0.87) but not CHD (RR 0.77 95% CI 0.55 to 1.09) or mortality (RR 0.86 95% CI 0.68 to 1.09).

A systematic review 2 included 29 studies with a total of 162 341 subjects. Regimens based on ACE inhibitors (22%, 95% CI 17 to 27) or calcium antagonists (18%, 95% CI 5 to 29) reduced the relative risks of total major cardiovascular events in placebo-controlled studies. ARB-based regimens reduced the risks of total major cardiovascular events (10%, 95% CI 4 to 17) compared with control regimens.

A systematic review and meta-analysis 3 included 123 studies with a total of 613 815 subjects. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure reduced the risk of major cardiovascular disease events (RR 0.80, 95% CI 0.77 to 0.83), coronary heart disease (RR 0.83, 95% CI 0.78 to 0.88), stroke (RR 0.73, 95% CI 0.68 to 0.77), and heart failure (RR 0.72, 95% CI 0.67 to 0.78). All-cause mortality was reduced by 13% (RR 0.87, 95% CI 0.84 to 0.91). Beta-blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium-channel-blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes.

    References

    • Wright JM, Musini VM, Gill R. First-line drugs for hypertension. Cochrane Database Syst Rev 2018;(4):CD001841. [PubMed]
    • Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003 Nov 8;362(9395):1527-35. [PubMed]
    • Ettehad D, Emdin CA, Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016;387(10022):957-967. [PubMed]

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