Diuretic Versus α-Blocker as First-Step Antihypertensive Therapy

Abstract

Abstract-The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an ␣-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged Ն55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over ␣-blocker-based antihypertensive treatment for the prevention of CVD.

Achieving blood preSsure goals sTudy in uncontrolled hypeRtensive pAtients treated with a fixed-dose combination of ramipriL / hydrochlorothiazide : the ASTRAL study

“…This is a controversial topic but it has never been shown in a large outcome study that new-onset diabetes worsens outcomes 24. Although there was no measurement of blood glucose in this study there were no reported cases of new-onset diabetes.…”

Mortality and Morbidity During and After Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

“…ALLHAT has reported analyses using achieved BP levels as time-dependent covariates in a Cox proportional hazard regression model showing that after adjustment for BP, the differences in risk of stroke and HF between treatment arms remain statistically significant, with only slight reduction in the hazard ratios. 10,14, 17, 30 Also, in this previous summary, 29 it was noted that at doses equivalent to that used in ALLHAT (chlorthalidone, average of 20 mg/day), it is likely that attributes of chlorthalidone extend to the class of thiazide and thiazide-type diuretics.…”

“…10 Results for the doxazosin arm, which was terminated early, have been reported in several papers, and are not included here. 11–17 …”

Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment

“…Overall, the ALLHAT study showed that those randomized to the diuretic chlorthalidone had fewer CVD events than those randomized to the other study treatments 16–18 . Those findings are replicated in the GenHAT subpopulation.…”