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

Abstract

To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in gender subgroups, we carried out a prespecified subgroup analysis of 15,638 female and 17,719 male participants in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure, or peripheral vascular disease), and end-stage renal disease. In-trial rates of heart failure, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared to chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared to chlorthalidone in both men and women. There were no significant treatment gender interactions. These findings did not persist through the extension period with the exception of the heart failure result for amlodipine versus chlorthalidone, which did not differ significantly by gender. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of heart failure. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men.

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population‐based study

“…28 Our study indicates that TDs are an effective antihypertensive therapy and, according to the literature, are likely cost-effective.…”

Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT

“…Similarly, the number to treat to prevent a stroke for lisinopril versus amlodipine is 111 patients. In-trial differences were mainly driven by race (race-by-lisinopril/chlorthalidone interaction P =0.005, race-by-amlodipine/lisinopril interaction P =0.012), where 6-year rates/100 persons were 6.2 for chlorthalidone, 5.8 for amlodipine, and 8.2 for lisinopril for Blacks, and separately by gender (gender-by-amlodipine/lisinopril interaction P =0.041), where 6-year rates/100 persons were 5.3 for chlorthalidone, 4.5 for amlodipine, and 6.3 for lisinopril for women (Table 2, Figures 2–3) (19). In-trial stroke rates were similar among treatment comparisons in non-Blacks and in men.…”

“…No in-trial versus post-trial treatment interactions affecting stroke were detected. Among women, lisinopril treatment was less effective than either chlorthalidone (HR=1.22, 95% CI 1.01–1.46) or amlodipine (HR=1.45, 95% CI 1.17–1.79) treatment in preventing in-trial stroke (19). These differences occurred in both Black and non-Black women, but were particularly marked in Black women, in whom lisinopril treatment was associated with a 35% higher rate of stroke compared to chlorthalidone treatment and a 48% higher rate compared with amlodipine treatment.…”

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

“…First, in the Veterans Administration Cooperative Study (V-HeFT), patients receiving prazosin experienced worse outcomes than those receiving the combined vasodilator therapy of isosorbide dinitrate and hydralazine [ 111 ]. Then, in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study, the doxazosin arm was terminated early because of the higher incidence of heart failure [ 112 ]. Mounting evidence indicates that the central nervous system plays a crucial role in the sympathetic excitation observed in heart failure.…”