Cardiovascular disease lisinopril

The doxazosin arm was terminated early when a significantly higher risk of heart failure compared with chlorthalidone was observed." The other arms were continued as scheduled, and no significant differences in the primary end point were seen between chlorthalidone and either lisinopril or amlodipine. However, chlorthalidone had statistically fewer secondary end points than amlodipine (heart failure) and lisinopril (combined cardiovascular disease, heart failure, and stroke). The study conclusions were that chlorthalidone was superior in preventing one or more major forms of cardiovascular disease and was less expensive than amlodipine and lisinopril. 

The study cohort was derived from 33,357 ALLHAT participants, who were aged 55 years or older, had hypertension and at least one additional cardiovascular disease risk factor. The participants who were normokalemic at baseline were randomised to chlorthalidone versus amlodipine or lisinopril and were stratified by level of potassium at year 1 into hypokalemia (<3.5 mmol/L) normokalemia (3.5-5.4 mmol/L) and hyperkalemia (>5.4 mmol/L). Incidence of hypokalemia in chlorthalidone was 12.9% and this differed significantly from amlodipine (2.1%, p < 0.001) and lisinopril (1.0%, p < 0.01). Incidence of hyperkalemia was greatest in lisinopril arm (3.6%) than in chlorthalidone arm (1.2%, p < 0.01) or amlodipine (1.9%, p < 0.01). Coronary heart disease occurred in 8.1%, 8.0% and 11% in patients with hypokalemia, normokalemia and hyperkalemia, respectively. 

In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), over 40 000 participants aged 55 years or older with hypertension and at least one other risk factor for coronary heart disease were randomized to chlortalidone, amlodipine, doxazosin, or lisinopril (1,2). Doxazosin was discontinued prematurely because chlortalidone was clearly superior in preventing cardiovascular events, particularly heart failure (2). Otherwise, mean follow-up was 4.9 years. There were no differences between chlortalidone, amlodipine, and lisinopril in the primary combined outcome or allcause mortality. Compared with chlortalidone, heart failure was more common with amlodipine and lisinopril, and chlortalidone was better than lisinopril at preventing stroke. 

The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was the deciding evidence that the JNC7 used to justify thiazide diuretics as first-line therapy." It was designed to test the hypothesis that newer antihypertensive agents (an a-blocker, ACE inhibitor, and dihydropyridine CCB) would be superior to thiazide diuretic therapy. The primary objective was to compare the combined end point of fatal coronary heart disease and nonfatal myocardial infarction. Other hypertension-related complications (e.g., heart failure and stroke) were evaluated as secondary end points. This was the largest hypertension trial ever conducted and included 42,418 patients aged 55 years and older with hypertension and one additional cardiovascular risk factor. This prospective, double-blind trial randomized patients to chlorthalidone (a thiazide diuretic), amlodipine (dihydropyridine CCB), doxazosin (a-blocker), or lisinopril (ACE inhibitor) for a mean follow-up of 4.9 years. 

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