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A Large Hypertension Trial, Focused on CAD Patients

No significant differences in outcome were found between a treatment regimen that included a calcium-channel antagonist and one that included a ß-blocker.

None of the large hypertension trials to date have been focused exclusively on patients with coronary artery disease (CAD). In this multicenter, open-label, randomized trial, researchers compared a calcium-channel-antagonist-based regimen with a ß-blocker-based regimen in 22,576 patients with both CAD and hypertension.

Patients received either sustained-release verapamil (a calcium-channel antagonist) or atenolol (a ß-blocker). If needed, the angiotensin-converting-enzyme inhibitor trandolapril and hydrochlorothiazide were added (in that order) in the verapamil group, and hydrochlorothiazide and trandolapril were added (in that order) in the atenolol group. However, trandolapril was added immediately for patients in both groups who had diabetes, renal impairment, or heart failure. At 24 months, most patients in both groups were receiving ACE inhibitors, and half were receiving at least 3 hypertension drugs.

During a mean follow-up of 2.7 years, no significant differences were found between the 2 groups in a combined endpoint (death, nonfatal myocardial infarction, or nonfatal stroke) or in any of the individual endpoints. Subgroup analyses generally were unrevealing. Blood pressure control and side effect profiles were similar in the 2 groups.

Comment: In these patients with CAD and hypertension, initial therapy with a calcium-channel antagonist or with a ß-blocker yielded similar outcomes. The sequencing of add-on therapy in this trial might be explained by the fact that the supporting drug company makes a combined verapamil-trandolapril tablet, which was used by patients in the verapamil arm. An editorialist concludes that this study -- which appropriately ended up as a comparison of 3-drug regimens for many patients -- adds little insight about any single drug.

— Allan S. Brett, MD

Published in Journal Watch General Medicine December 23, 2003

Citation(s):

Pepine CJ et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): A randomized controlled trial. JAMA 2003 Dec 3; 290:2805-16.

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Alderman MH. The return on INVEST. JAMA 2003 Dec 3; 290:2859-61.

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• Medline abstract (Free)