Newer vs. Older Antihypertensives: New Data, Same Controversy

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Newer vs. Older Antihypertensives: New Data, Same Controversy

Treatment of hypertension reduces risk for adverse cardiovascular events, but whether this effect varies among different classes of antihypertensive drugs when blood pressure is comparably reduced is unclear. Results from the ALLHAT trial (Journal Watch Jan 14 2003) revealed little difference in the primary endpoint of coronary death or nonfatal myocardial infarction among patients who took chlorthalidone or newer drugs (amlodipine, lisinopril, or doxazosin). Now, in another large trial, sponsored by the manufacturer of amlodipine, researchers compared clinical outcomes with newer and older antihypertensive medications.

Investigators randomized 19,257 patients (age range, 40–79; with hypertension and at least three other cardiovascular risk factors) to amlodipine (with perindopril added first, if needed) or atenolol (with the diuretic bendroflumethiazide added first, if needed). Doses were escalated, and drugs were added systematically to achieve BP targets of 130/80 mm Hg for diabetics and 140/90 mm Hg for nondiabetics.

After a median 5.5 years of follow-up, 32% of diabetics and 60% of nondiabetics had reached their target BPs. The treatment groups had comparable BPs at baseline, but the amlodipine group had lower BPs throughout the trial (average difference, 2.7/1.9 mm Hg). The primary endpoint, cardiac death or nonfatal MI, was nonsignificantly less common in the amlodipine group than in the atenolol group; most secondary endpoints (e.g., adverse coronary events, cardiovascular mortality, all-cause mortality, stroke) were significantly less common in the amlodipine group.

Comment: This trial was weakened by the greater BP reduction in the amlodipine group. Results from a second paper by the same authors and an accompanying editorial disagree on whether the BP difference explains some or all of the outcome differences. The editorialists conclude that the choice of antihypertensive drug remains less important than the BP reduction achieved. They also point out that the results of this study in high-risk patients might not be generalizable to healthier populations.

— Bruce Soloway, MD

Published in Journal Watch General Medicine October 21, 2005

Citation(s):

Dahlöf B et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomised controlled trial. Lancet 2005 Sep 10; 366:895-906.

Medline abstract (Free)

Poulter NR et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet 2005 Sep 10; 366:907-13.