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Heidenreich PA, Davis BR, Cutler JA, Furberg CD, Lairson DR, Shlipak MG, Pressel SL, Nwachuku C, Goldman L. Cost-effectiveness of chlorthalidone, amlodipine, and lisinopril as first-step treatment for patients with hypertension: an analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Journal of general internal medicine. 2008 May 1; 23(5):509-16.
OBJECTIVE: To evaluate the cost-effectiveness of first-line treatments for hypertension. BACKGROUND: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) found that first-line treatment with lisinopril or amlodipine was not significantly superior to chlorthalidone in terms of the primary endpoint, so differences in costs may be critical for optimizing decision-making. METHODS: Cost-effectiveness analysis was performed using bootstrap resampling to evaluate uncertainty. RESULTS: Over a patient's lifetime, chlorthalidone was always least expensive (mean $4,802 less than amlodipine, $3,700 less than lisinopril). Amlodipine provided more life-years (LYs) than chlorthalidone in 84% of bootstrap samples (mean 37 days) at an incremental cost-effectiveness ratio of $48,400 per LY gained. Lisinopril provided fewer LYs than chlorthalidone in 55% of bootstrap samples (mean 7-day loss) despite a higher cost. At a threshold of $50,000 per LY gained, amlodipine was preferred in 50%, chlorthalidone in 40%, and lisinopril in 10% of bootstrap samples, but these findings were highly sensitive to the cost of amlodipine and the cost-effectiveness threshold chosen. Incorporating quality of life did not appreciably alter the results. Overall, no reasonable combination of assumptions led to 1 treatment being preferred in over 90% of bootstrap samples. CONCLUSIONS: Initial treatment with chlorthalidone is less expensive than lisinopril or amlodipine, but amlodipine provided a nonsignificantly greater survival benefit and may be a cost-effective alternative. A randomized trial with power to exclude "clinically important" differences in survival will often have inadequate power to determine the most cost-effective treatment.