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

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 (n 9048) or lisinopril (n 9054). 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 (RR 1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR 1.07, 95% CI 0.89 to 1.28), and in women (RR 1.45, 95% CI 1.17 to 1.79), but not in men (RR 1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR 1.06, 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 (RR 0.87, 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. (Hypertension. 2006;48:374-384.)

[1]  Li-sheng Liu,et al.  The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients , 2005, Journal of hypertension.

[2]  S. Kjeldsen,et al.  Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The value randomised trial☆ , 2004 .

[3]  B. Davis,et al.  The prevalence of reduced glomerular filtration rate in older hypertensive patients and its association with cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. , 2004, Archives of internal medicine.

[4]  B. Davis,et al.  Cardiovascular Outcomes Using Doxazosin vs. Chlorthalidone for the Treatment of Hypertension in Older Adults With and Without Glucose Disorders: A Report From the ALLHAT Study , 2004, Journal of clinical hypertension.

[5]  K. Fox,et al.  Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study) , 2003, The Lancet.

[6]  L. Wilkins.  Diuretic Versus &agr;-Blocker as First-Step Antihypertensive Therapy: Final Results From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) , 2003 .

[7]  D. Bennett,et al.  Blood pressure and cardiovascular disease in the Asia Pacific region. , 2003, Journal of hypertension.

[8]  S. Lewington.  Prospective studies collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies (vol 360, pg 1903, 2002) , 2003 .

[9]  R. Collins,et al.  Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies , 2002, The Lancet.

[10]  Tom Greene,et al.  Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. , 2002, JAMA.

[11]  T. Lumley,et al.  Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study. , 2002, Archives of internal medicine.

[12]  M. Woodward,et al.  Randomised trial of a perindopril-based blood pressure lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack , 2001 .

[13]  W. Cushman,et al.  Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) , 2001, Hypertension.

[14]  J. Williamson,et al.  Patterns of Self‐Rated Health in Older Adults Before and After Sentinel Health Events , 2001, Journal of The American Geriatrics Society.

[15]  M. Pahor,et al.  Use of calcium antagonists and hemoglobin loss in hospitalized elderly patients: A cohort study , 2000, Clinical pharmacology and therapeutics.

[16]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[17]  T. Hedner,et al.  Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study , 1999, The Lancet.

[18]  M. Proschan.  A multiple comparison procedure for three- and four-armed controlled clinical trials. , 1999, Statistics in medicine.

[19]  L. Niskanen,et al.  Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial , 1999, The Lancet.

[20]  S. Shapiro,et al.  Major upper gastrointestinal bleeding and the use of calcium channel blockers , 1999, The Lancet.

[21]  W. Ray,et al.  No association between calcium channel blocker use and confirmed bleeding peptic ulcer disease. , 1998, American journal of epidemiology.

[22]  B. Psaty,et al.  Health Outcomes Associated with Antihypertensive Therapies Used as First-Line Agents: A Systematic Review and Meta-analysis , 1998 .

[23]  J. Klein,et al.  Survival Analysis: Techniques for Censored and Truncated Data , 1997 .

[24]  L. Ferrucci,et al.  Calcium-channel blockade and incidence of cancer in aged populations , 1996, The Lancet.

[25]  N. Brown,et al.  Increased sensitivity to bradykinin among African Americans. , 1996, The Journal of allergy and clinical immunology.

[26]  J. Guralnik,et al.  Do calcium channel blockers increase the risk of cancer? , 1996, American journal of hypertension.

[27]  J. Guralnik,et al.  Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old , 1996, The Lancet.

[28]  Michael A. Proschan,et al.  Rationale and Design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) , 1996 .

[29]  B. Psaty,et al.  Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. , 1995, Circulation.

[30]  R. Fogari,et al.  Effects of different antihypertensive drugs on plasma fibrinogen in hypertensive patients. , 1995, British journal of clinical pharmacology.

[31]  E. J. Brown,et al.  Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. , 1992, The New England journal of medicine.

[32]  S. Yusuf,et al.  Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. , 1992, The New England journal of medicine.