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Central pressure changes may give advantage to amlodipine.

DALLAS -- Brachial blood pressure measurements may not be the best way to assess the effects that antihypertensive drugs have on blood pressure.

An amlodipine-based regimen was much better than atenolol-based treatment for lowering central aortic pressure in a sub-study of a trial that involved a total of more than 19,000 patients, Bryan Williams, M.D., said at the annual scientific sessions of the American Heart Association.

The results "demonstrate for the first time in a large, clinical-outcomes trial that blood-pressure lowering drugs have profoundly different effects on central aortic pressures and hemodynamics despite a similar impact on brachial blood pressure," said Dr. Williams, who is a professor of medicine at the University of Leicester (U.K.).

Amlodipine's ability to substantially reduce central aortic pressure is likely a major reason why the clinical results from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that patients treated with an amlodipine-based regimen had a 16% relative reduction in the incidence of total cardiovascular events and procedures, compared with patients treated with an atenolol-based regimen during an average follow-up of 5.5 years (Lancet 2005;366:895-906).

"It's remarkable that we're talking about what these drugs do in the central aorta after years of being completely blind" to these effects, Dr. Williams said. Multiple measures of central aortic pressures were obtained for 2,199 of the patients enrolled in ASCOT. These measures were obtained via a commercially available device that calculates central aortic pressures after transcutaneously measuring the radial artery waveform through an external transducer wand that's placed on a patient's wrist.

"Systolic pressure is not constant throughout the arterial tree, and clinically relevant changes may not be measured by brachial-cuff blood pressure," commented Joseph L. Izzo Jr., M.D., professor of medicine and pharmacology at the State University of New York at Buffalo. "We now have a mandate to look beyond blood-pressure cuff measurements."

The ASCOT substudy was done at five participating hospitals in the United Kingdom and Ireland. Participating patients had their central aortic pressures measured at baseline and during multiple follow-up examinations using the Sphygmo-Cor Px system. Like all participants in ASCOT, these hypertensive patients were randomized to treatment with either of two regimens: amlodipine, followed by perindopril when a second drug was needed to reach the goal brachial-artery pressure, or atenolol, with the diuretic bendroflumethiazide and potassium added when a second drug was needed.

Throughout treatment, patients on the amlodipine-based regimen maintained a central aortic systolic pressure that averaged 4.3 mm Hg lower than patients treated with the atenolol-based regimen. Central aortic pulse pressure averaged 3.0 mm Hg lower in the amlodipine group, reported Dr. Williams. Both cuts in pressure were statistically significant. In contrast, systolic pressure measured by brachial cuff averaged 0.7 mm Hg lower in the amlodipine group, compared with the atenolol group, and diastolic blood pressure averaged 1.6 mm Hg lower with amlodipine.

Dr. Williams and his associates analyzed the role of central aortic pressure and other measured variables on the incidence of 305 cardiovascular events, procedures, or episodes of renal impairment that occurred among the 2,199 patients during follow-up. In a multivariate analysis, central aortic pulse pressure was the only factor that produced a significant, independent effect on the rate of these outcomes.

Central aortic pressure is produced by a combination of the main, outgoing pressure wave and a wave that's reflected back from the arms. Amlodipine causes peripheral vasodilation that reduces the reflected wave and shifts it away from the heart; atenolol causes peripheral vasoconstriction that boosts the reflected wave and brings it closer to the heart, Dr. Williams said.

The ASCOT study and substudy were sponsored by Pfizer Inc. which markets amlodipine (Norvasc). Dr. Williams has been a consultant to and has received research grants from Pfizer.


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Title Annotation:Cardiovascular Medicine
Author:Zoler, Mitchel L.
Publication:Internal Medicine News
Geographic Code:1USA
Date:Dec 15, 2005
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