Choosing a first-line antihypertensive

In their systematic review of antihypertensive therapies, James M. Wright and colleagues conclude that "low-dose thiazide therapy can be prescribed as the first-line treatment of hypertension with confidence that the risk of death, coronary artery disease and stroke will be reduced. The same cannot be said for high-dose thiazide therapy, β-blockers, calcium-channel blockers or ACE [angiotensin-converting-enzyme] inhibitors."1 Although there may be good reasons for selecting thiazide therapy, such as low cost and low rate of withdrawal for adverse effects, the efficacy data in Table 4 do not support the authors' conclusions that only low-dose thiazide therapy will prevent death and cardiovascular morbidity in patients with hypertension.

Table 4 shows that there was essentially no difference among low-dose thiazide, high-dose thiazide, and calcium-channel blocker therapy with respect to mortality (relative risks 0.89, 0.90 and 0.86 respectively) or total cardiovascular events (relative risks 0.68, 0.72 and 0.71 respectively). For total cardiovascular events, a Mantel-Haenszel analysis2 finds no evidence of heterogeneity between these medications (χ2 = 3.6 on 2 degrees of freedom, p = 0.16). There was lower risk reduction for β-blockers than for the other medications, but there was no significant difference between the β-blockers and low-dose thiazide therapy for mortality (relative risk 1.01 and 0.89 respectively). For the β-blockers, the risk reduction for total cardiovascular events just failed to reach significance at the 5% level (relative risk 0.89, 95% confidence interval 0.78-1.02). There were no trials of ACE inhibitors against placebo, but the one trial comparing ACE inhibitors with calcium-channel blockers (Table 2) suggested that the ACE inhibitor was at least as good as the calcium-channel blockers in reducing mortality and cardiovascular events.

I conclude that the data presented by Wright and colleagues show that low- and high-dose thiazide therapy, calcium-channel blockers and ACE inhibitors are similarly efficacious in reducing mortality and cardiovascular events in patients with hypertension.