Beta-blocker-based therapy and calcium antagonist-based therapy are equally effective in treating hypertension in patients with coronary artery disease, according to an article in the December 3rd issue of The Journal of the American Medical Association.

According to background information in the article, although evidence of the effectiveness of medications to treat hypertension is conclusive, the safety and efficacy of antihypertensive medications in patients with coronary artery disease have been evaluated only through analyses of subgroups in large trials.

Carl J. Pepine, MD, and his international colleagues designed a randomized trial, the International Verapamil-Trandolapril Study (INVEST), to compare outcomes in older hypertensive patients with coronary artery disease treated with a calcium antagonist strategy (verapamil sustained release) or a beta-blocker strategy (trandolapril, hydrochlorothiazide, or both). Because most hypertensive patients require more than 1 agent to adequately control blood pressure, INVEST was intended to compare multidrug strategies rather than individual agents. The study included 22,576 patients aged 50 years or older, and was conducted September 1997 to February 2003 at 862 sites in 14 countries.

In 1 arm, trandolapril, hydrochlorothiazide, or both were administered according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: Goals were less than 140 mm Hg/less than 90 mm Hg or less than 130 mm /less than 85 mm Hg if patients had diabetes or renal impairment. Therapy in the other arm was based on sustained release verapamil with the same blood pressure goals.

After an average follow-up of 2.7 years per patient, 2,269 patients had a primary outcome event (death, nonfatal myocardial infarction, or nonfatal stroke) with no statistically significant difference between the treatment strategies (9.93 percent in calcium-antagonist-based therapy and 10.17 percent in beta-blocker-based therapy).

Blood pressure control over 2 years was also similar. Goals were achieved by 65.0 percent (systolic) and 88.5 percent (diastolic) of calcium-antagonist-based therapy patients and 64.0 percent (systolic) and 88.1 percent (diastolic) of beta-blocker-based therapy patients. A total of 71.7 percent of calcium antagonist patients and 70.7 percent of beta-blocker patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg.

"In conclusion, our results indicate that lower targets for blood pressure control can be achieved in most hypertensive patients with coronary artery disease using a multidrug strategy that includes administration of angiotensin-converting enzyme inhibitors to patients with heart failure, diabetes, or renal impairment. The clinical equivalence of the [2 treatment] groups in prevention of death, myocardial infarction, or stroke supports the use of either strategy in clinically stable patients with coronary artery disease who require blood pressure control. The decision regarding which drug classes to use in specific patients should be based on additional factors including adverse experiences, history of heart failure, diabetes risk, and the physician's best judgment," the authors concluded.

In an accompanying editorial, Michael H. Alderman, MD, wrote that despite the large scale and extensive follow-up of INVEST, its design (which permitted rational manipulation of therapy) and the application of diuretics and angiotensin-converting enzyme inhibitors for most patients in both groups combined to attenuate distinctions between drug therapies.

"Under these study conditions, it did not seem to matter whether the calcium antagonist verapamil or the beta-blocker atenolol were included in a treatment regimen. Thus, when global risk assessment determines that blood pressure should be reduced, the answer remains that diuretics should usually come first, with blockade of the renin-angiotensin system a close second," he wrote.