Clinical Events in High-Risk Hypertensive Patients Randomly Assigned to Calcium Channel Blocker Versus Angiotensin-Converting Enzyme Inhibitor in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Abstract

Abstract-The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (nϭ9048) or lisinopril (nϭ9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RRϭ1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RRϭ1.07, 95% CI 0.89 to 1.28), and in women (RRϭ1.45, 95% CI 1.17 to 1.79), but not in men (RRϭ1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RRϭ1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RRϭ0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm. Key Words: antihypertensive therapy Ⅲ hypertension, detection and control Ⅲ calcium channel blockers Ⅲ angiotensin-converting enzyme Ⅲ cardiovascular diseases Ⅲ stroke Ⅲ heart failure T he success in the management of hypertension and prevention of its sequelae is owed, in part, to the many antihypertensive drugs available to physicians and patients. By the early 1990s, all of the classes of antihypertensive drugs were shown effective in lowering blood pressure (BP), but few morbidity and mortality efficacy data were available except for thiazide-type diuretics and ␤-blockers. Angiotensin-converting enzyme (ACE) inhib-

Use of dihydropyridine calcium channel blockers in the management of hypertension in Eastern Asians: A scientific statement from the Asian Pacific Heart Association

“…LIving with Systolic Hypertension), 33 ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), 34,35 ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) 36 and VALUE (Valsartan Antihypertensive Long-term Use Evaluation) 37 trials with amlodipine, the STOP-2 (Swedish Trial in Old Patients with hypertension-2) trial with felodipine and isradipine 38 and the INSIGHT (International Nifedipine GITS Study-Intervention as a Goal for Hypertension Therapy) trial with nifedipine GITS. 39 In the amlodipine trials, [33][34][35][36][37] amlodipine reduced systolic blood pressure slightly less than chlothalidone (+1.0 mm Hg) 34 and slightly more than lisinopril in ALLHAT (À1.5 mm Hg), 35 valsartan in VALUE (À2.0 mm Hg), 37 atenolol in ASCOT (À2.8 mm Hg) 36 and hydrochlorothiazide in ACCOMPLISH (À0.9 mm Hg).…”

“…39 In the amlodipine trials, [33][34][35][36][37] amlodipine reduced systolic blood pressure slightly less than chlothalidone (+1.0 mm Hg) 34 and slightly more than lisinopril in ALLHAT (À1.5 mm Hg), 35 valsartan in VALUE (À2.0 mm Hg), 37 atenolol in ASCOT (À2.8 mm Hg) 36 and hydrochlorothiazide in ACCOMPLISH (À0.9 mm Hg). 33 Amlodipine provided similar or increased protection against stroke and myocardial infarction in comparison with chlothalidone (À7 and À2%), 34 lisinopril (À23% (P¼0.003) and À1%), 35 valsartan (À15% (P¼0.08) and À19% (P¼0.02)), 37 atenolol (À23% (P¼0.0003) and À13% (P¼0.05)) 36 and hydrochlorothiazide (À16 and À22% (P¼0.04)). 33 In the STOP-2 trial, felodipine or isradipine was compared with the ACE inhibitor and diuretic/b-blocker groups.…”

Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes

“…Response to antihypertensive treatment also varies among individuals with some individuals remaining resistant to certain therapies, and only about 50% of patients treated with antihypertensive therapies achieve blood pressure (BP) control 1, 3, 4, 5. Ethnic differences regarding both side effects and drug efficacy have been noted between white and black populations prescribed antihypertensives 3, 5.…”

How early should blood pressure control be achieved for optimal cardiovascular outcomes?

“…13 In a subsequent report based on further analyses that stratified patients according to gender and race (black versus non-black), and focused on the ACEI and CCB arms, suboptimal BP-lowering effects for lisinopril were evident among black men and women. 14 Black ACEI recipients did not experience the sharp, pronounced BP reductions achieved by their non-black counterparts during the first 6 months of ALLHAT ( Figure 1) and had significantly higher rates of stroke when compared with CCB-treated black patients.…”