Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Calcium antagonists reduce the risk for restenosis after coronary angioplasty

ACP J Club. 1994 Sept-Oct;121:41. doi:10.7326/ACPJC-1994-121-2-041


Source Citation

Hillegass WB, Ohman EM, Leimberger JD, Califf RM. A meta-analysis of randomized trials of calcium antagonists to reduce restenosis after coronary angioplasty. Am J Cardiol. 1994 May 1;73:835-9.


Abstract

Objective

To evaluate the effectiveness of calcium antagonists in reducing angiographic restenosis in patients who have had coronary angioplasty.

Data Sources

MEDLINE was searched for the years 1980 to June 1993 for studies that used calcium antagonists to prevent restenosis after angioplasty. Abstracts of presentations from meetings of the American College of Cardiology, the American Heart Association, and the European Congress of Cardiology from 1980 to 1993 were reviewed; and the articles cited by all located studies were retrieved.

Study Selection

Studies were selected if patients were randomly assigned and one of the treatment groups received a calcium antagonist. The trials had to have been previously published as a journal article or meeting abstract in English. 5 studies comprising 919 patients met the inclusion criteria.

Data Extraction

Baseline patient characteristics (diabetes, unstable angina, lesion severity), study design (placebo-controlled), treatment of crossover patients (drug-intolerant or noncompliant), follow-up rates (angiography), angiographic methods and definitions, and results.

Main Results

3 trials reported the number of patients with diabetes, 2 trials reported the number of patients with unstable angina, and all 5 trials reported the severity of pre- and post-procedure lesion stenosis in patients. 3 trials reported compliance, which was ≥ 78%. Follow-up angiography ranged from 60% to 100% with an overall rate of 82%. Patients receiving calcium antagonists had an approximate 30% reduction in relative risk for restenosis (common odds ration [COR], 0.68; 95% CI, 0.49 to 0.94). The risk for restenosis was not affected by exclusion of the trial without placebo (COR, 0.68; CI, 0.49 to 0.96) nor by the inclusion of 23 patients who had follow-up exercise stress testing but not angiography in 1 trial (COR, 0.70; CI, 0.51 to 0.96). The observed treatment effects were homogeneous across trials (Breslow and Day statistic, 4.06; P = 0.40).

Conclusion

Calcium antagonists reduce the odds of restenosis by approximately 30% in patients at risk after coronary angioplasty.

Source of funding: Not stated.

For article reprint: Dr. William B. Hillegass, Box 3386, Duke University Medical Center, Durham, NC 27710.


Commentary

Restenosis after coronary angioplasty is the main limiting factor to the long-term efficacy of the procedure. For example, in the angioplasty arm of the Randomised Intervention Treatment of Angina study (1), the 2-year probability of repeat angioplasty, coronary artery grafting, myocardial infarction, or death was 38%. Because more than 300 000 coronary angioplasties are now done annually in the United States alone, restenosis causes substantial morbidity, mortality, and health care expenditure. Although several risk factors have been defined, no pharmacologic intervention has been clearly shown to reduce risk (2). This meta-analysis pools data from trials of diltiazem, verapamil, and nifedipine and provides strong evidence for the efficacy of calcium antagonists as a class. Data on only 919 patients were included, and the authors rightly caution against the general adoption of this treatment strategy until a larger randomized trial has confirmed its efficacy and safety. Another approach, using a monoclonal antibody fragment directed against the platelet glycoprotein IIb/IIIa integrin, has recently been reported to reduce clinical restenosis in high-risk patients (3). Thus, at least 2 promising lines of research to pursue against this previously intractable problem now exist. Inclusion of suitable patients in further large, well-designed randomized trials offers the best prospect of rapid general improvement in the outcome of coronary angioplasty.

Kent L. Woods, MD
University of Leicester Leicester, England, United Kingdom