According to background information in the article, despite conclusive evidence of the effectiveness of medications to treat high blood pressure in patients with hypertension in general, safety and efficacy of antihypertensive medications in patients with coronary artery disease (CAD) have been discerned only from the analyses of subgroups in large trials.
Carl J. Pepine, M.D., of the University of Florida College of Medicine, Gainesville, Fla., and colleagues designed a randomized trial, the International Verapamil-Trandolapril Study (INVEST), to compare outcomes in older hypertensive patients with CAD treated with a calcium antagonist strategy (CAS; verapamil sustained release [SR]) or a beta-blocker, non-calcium antagonist strategy (NCAS; atenolol). 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 hypertensive CAD patients aged 50 years or older, and was conducted September 1997 to February 2003 at 862 sites in 14 countries.
The medications trandolapril and/or hydrochlorothiazide were administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment.
After an average follow-up of 2.7 years per patient, 2,269 patients had a primary outcome event (death, nonfatal heart attack, or nonfatal stroke) with no statistically significant difference between treatment strategies (9.93 percent in CAS and 10.17 percent in NCAS). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0 percent (systolic) and 88.5 percent (diastolic) of CAS patients and 64.0 percent (systolic) and 88.1 percent (diastolic) of NCAS patients. A total of 71.7 percent of CAS patients and 70.7 percent of NCAS 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 CAD using a multidrug strategy that includes administration of angiotensin-converting enzyme (ACE) inhibitors to patients with heart failure, diabetes, or renal impairment. The clinical equivalence of the CAS and NCAS groups in prevention of death, [heart attack], or stroke supports the use of either strategy in clinically stable patients with CAD who require blood pressure control. The decision regarding which drug classes to use in specific CAD patients should be based on additional factors including adverse experiences, history of heart failure, diabetes risk, and the physician's best judgment," the authors write.
(JAMA. 2003;290:2805-2816. Available post-embargo at JAMA.com)
Editor's Note: For information on the funding/support for the study and the financial disclosures of the authors, please see the JAMA article.
EDITORIAL: THE RETURN ON INVEST
In an accompanying editorial, Michael H. Alderman, M.D., of the Albert Einstein College of Medicine, Bronx, N.Y., writes 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 ACE inhibitors for most patients in both groups, have 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 [an enzyme produced by the kidney, plus a substance which constricts small arteries] a close second," he writes. (JAMA. 2003;290:2859-2860. Available post-embargo at JAMA.com)
Editor's Note: Dr. Alderman receives research support from GlaxoSmithKline and Merck and has received honoraria for speaking engagements from Pfizer, Merck, and Novartis.
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