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18-11-2009 | Cardiology | Article

Chlorthalidone preferred over amlodipine, lisinopril as initial anti-hypertensive therapy in long-term ALLHAT follow-up

MedWire News: Ten-year follow-up of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial confirmed the results from the 5-year trial demonstrating that an older drug, chlorthalidone, was as effective as drugs considered newer at the time the trial was initiated (ie, the calcium-channel blocker amlodipine, the ACE inhibitor lisinopril, and the alpha blocker doxazosin.

“In the 10-year post-trial follow-up, any small differences between chlorthalidone and the newer treatments disappeared, except for an excess of heart failure (HF) for amlodipine compared with chlorthalidone. No new adverse events emerged over longer follow-up. These results support the recommendations of the JNC 7 – to initiate anti-hypertensive therapy with a diuretic,” said William Cushman (Veterans Affairs Medical Center, Memphis, Tenessee, USA), who presented these findings at the American Heart Association 2009 Scientific Sessions in Orlando, Florida, USA. “These results suggest that chlorthalidone should be preferred, and that amlodipine, lisopril, or doxazosin are not superior drugs. Chlorthalidone was superior to each of the other three drugs in preventing the occurrence of one or more major adverse cardiovascular event (MACE),” Cushman said.

The randomized, double-blind, multicenter ALLHAT trial included 42,418 high-risk people with hypertension aged 55 years or older. At 5-year follow-up, amlodipine was not superior to chlorthalidone for any of the outcomes assessed, including coronary heart disease, all-cause mortality, cardiovascular disease mortality, stroke, HF, or end-stage renal disease. The amlodipine group had a 34% excess in HF compared with chlorthalidone. Lisinopril had 10% more cardiovascular events, 19% more HF, and 15% more stroke events compared with chlorthalidone. The rate of HF was 40% higher in African Americans who received lisinopril versus chlorthalidone. The doxazosin arm was closed prematurely at 3 years when an excess of cardiovascular events was found.

The 10-year follow-up was based on the trial data, as well as several large administrative databases, including Medicare. For this analysis, there was no information on additional drugs ALLHAT participants took after the trial ended. No difference in all-cause mortality was found between chlorthalidone and the other two drugs in 41,719 evaluable patients. No difference in cardiovascular mortality or coronary heart disease was found among the three drugs in the 27,246 patients included in that analysis.

Cushman said the HF difference persisted for amlodipine, but was no longer significant for lisinopril versus chlorthalidone after 10 years. A slightly lower incidence of cardiovascular disease was found for lisinopril.

“These results should not be construed as recommending lisinopril over chlorthalidone for the treatment of hypertension,” Cushman said.

In the USA, JCN 7 guidelines recommend a thiazide diuretic as first-line treatment for hypertension. The guidelines of the European Society of Hypertension and the European Society of Cardiology express no preference for starting drug. In the UK, thiazides and beta-blockers are discouraged, explained formal discussant of the presentation Daniel Jones (University of Mississippi, Oxford, Missouri, USA).

“An alternative interpretation of this trial is that several classes of drug provide cardiovascular protection and lower blood pressure. Blood pressure should be lowered with the least intrusive approach for an individual patient” Jones stated.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Sara Freeman

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