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Antihypertensive & Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) study

Study characteristics: - double-blind, randomized trial - 33,357* people > 54 years of age - hypertension with at least 1 other coronary risk factor - mean blood pressure (baseline) = 146/84 mm Hg (from graphs of data) - nearly 1/2 women, > 1/3 with diabetes mellitus - average follow-up of 5 years * 10,000 also studied for statin therapy - LDL cholesterol 120-189 mg/dL, 100-120 gm/dL (if documented CAD) Patients received either: a) chlorthalidone (thiazide diuretic) b) amlodipine (Ca+2 channel blocker) c) lisinopril (ACE inhibitor) d) doxazosin (alpha-blocker) * pravastatin 40 mg QD Patients who need additional blood pressure control received either atenolol, reserpine or clonidine (not blinded) * The doxazosin arm was terminated early (2000) because of a high incidence of congestive heart failure Primary outcome: mycardial infarction (MI) Secondary outcomes: 1) all-cause mortality 2) CHD: combined MI, PCI, acute coronary syndrome 3) CVD: combined CHD, stroke, angina without hospitalization, heart failure, peripheral arterial disease Conclusions: 1) NO differences in mortality or myocardial infarction in the 3 groups 2) thiazide (chlorthalidone) AS effective as ACE inhibitor (lisinopril) or calcium channel blocker (amlodipine) in preventing myocardial infarction or mortality resulting from coronary artery disease 3) thiazide MORE effective than ACE inhibitor or calcium channel blocker for preventing heart failure or stroke a) amlodipine associated with 38% higher risk of heart failure than chlorthalidone (13.2% vs 7.7%) b) lisinopril vs chlorthalidone 1] 15% higher risk of stroke (6.3% vs 5.6%) 2] 19% higher risk of heart failure (8.7% vs 7.7%) a] relative risk 2.08 year 1 b] no difference beyond year 1 [6] 3] 11% higher risk of angina (13.6% vs 12.1%) 4) no difference in myocardial infarction or in all cause mortality at 5 years in statin arm of trial 5) creatinine-based measures of renal function were more favorable in the amlodipine &/or lisinopril groups; however, rates of end-stage renal disease (ESRD) & rate of decline of glomerular filtration rate (GFR) to 50% of its initial value were not significantly in the 3 groups [5] 6) mean blood pressure after 6 years 134/74 mm Hg a) 5-year systolic blood pressures significantly higher in amlodipine (0.8 mm Hg) & lisinopril (2 mm Hg) groups compared with chlorthalidone b) 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg) c) systolic blood pressure differences among groups greatest in 1st year Limitations of study: 1) looks ONLY at initial treatment 2) overlooks observation that incidence of diabetes lower with ACE inhibitor than with thiazide diuretic 3) does NOT achieve similar blood pressure reduction in groups - systolic blood pressure reduction greatest in thiazide group 4) only compares 4 different antihypertensives Notes: - lisinopril, but not amlodipine seems to protect against cardiac conduction system defects relative to chlorthalidone (RR=0.81) [7]

General

hypertension clinical trials

References

  1. Prescriber's Letter 10(1):1 2003
  2. Journal Watch 23(3):21, 2003 Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18;288(23):2981-97. PMID: 12479763
  3. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002 Dec 18;288(23):2998-3007. PMID: 12479764
  4. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) http://www.nhlbi.nih.gov/health/allhat/index.htm
  5. Journal Watch 25(12):99, 2005 Rahman M, Pressel S, Davis BR, Nwachuku C, Wright JT Jr, Whelton PK, Barzilay J, Batuman V, Eckfeldt JH, Farber M, Henriquez M, Kopyt N, Louis GT, Saklayen M, Stanford C, Walworth C, Ward H, Wiegmann T. Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2005 Apr 25;165(8):936-46. PMID: 15851647
  6. Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, Goff D, Leenen F, Mohiuddin S, Papademetriou V, Proschan M, Ellsworth A, Golden J, Colon P, Crow R; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1. PMID: 16651474 - Yusuf S. Preventing vascular events due to elevated blood pressure. Circulation. 2006 May 9;113(18):2166-8. No abstract available. PMID: 16684871
  7. Dewland TA, Soliman EZ, Davis BR et al Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease. JAMA Intern Med. 2016 Aug 1;176(8):1085-1092. PMID: 27367818 - Narayan SM, Baykaner T, Maron DJ. Can Cardiac Conduction System Disease Be Prevented? JAMA Intern Med. 2016 Aug 1;176(8):1093-1094. PMID: 27367299