First-Line Treatment for Hypertension

Background: Sustained elevated blood pressure, unresponsive to lifestyle measures, leads to a critically important clinical question: What class of drug is the best first-line option? This review answers that question. Objectives: To quantify the benefits and harms of the major first-line antihypertensive drug classes: thiazides, beta blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, alpha blockers, and angiotensin receptor blockers. Search Strategy: Electronic search of Medline (January 1966 through June 2008), EMBASE, CINAHL, and the Cochrane clinical trial register, using standard search strategy of the hypertension review group with additional terms. Selection Criteria: Randomized trials of at least one year duration comparing one of six major drug classes with placebo or no treatment. More than 70 percent of participants must have blood pressure greater than 140/90 mm Hg at baseline. Data Collection and Analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD), cardiovascular events, decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. Risk ratio (RR) and a fixed effects model were used to combine outcomes across trials. Main Results: Of 57 trials identified, 24 trials with 28 arms (n = 58,040) met the inclusion criteria. Thiazides (19 randomized controlled trials (RCTs)) reduced mortality (RR = 0.89; 95% confidence interval ICI], 0.83 to 0.96), stroke (RR = 0.63; 95% Cl, 0.57 to 0.71), CHD (RR = 0.84; 95% Cl, 0.75 to 0.95), and cardiovascular events (RR = 0.70; 95% Cl, 0.66 to 0.76). Low-dose thiazides (eight RCTs) reduced CHD (RR = 0.72; 95% Cl, 0.61 to 0.84), but high-dose thiazides (11 RCTs) did not (RR = 1.01; 95% Cl, 0.85 to 1.20). Beta blockers (five RCTs) reduced stroke (RR = 0.83; 95% Cl, 0.72 to 0.97) and cardiovascular events (RR = 0.89; 95% Cl, 0.81 to 0.98), but not CHD (RR = 0.90; 95% Cl, 0.78 to 1.03) or mortality (RR = 0.96; 95% Cl, 0.86 to 1.07). ACE inhibitors (three RCTs) reduced mortality (RR = 0.83; 95% Cl, 0.72 to 0.95), stroke (RR = 0.65; 95% Cl, 0.52 to 0.82), CHD (RR = 0.81; 95% Cl, 0.70 to 0.94), and cardiovascular events (RR = 0.76; 95% Cl, 0.67 to 0.85). Calcium channel blockers (one RCT) reduced stroke (RR = 0.58; 95% CI, 0.41 to 0.84) and cardiovascular events (RR = 0.71; 95% Cl, 0.57 to 0.87), but not CHD (RR = 0.77; 95% Cl, 0.55 to 1.09) or mortality (RR = 0.86; 95% CI, 0.68 to 1.09). No RCTs were found for angiotensin receptor blockers or alpha blockers. Authors' Conclusions: First-line low-dose thiazides reduce all morbidity and mortality outcomes. ACE inhibitors and calcium channel blockers may be similarly effective, but the evidence is less robust. First-line high-dose thiazides and beta blockers are inferior to first-line low-dose thiazides.