Effect of combined heparin and aspirin on outcomes in unstable angina

CLINICAL QUESTION

Will the addition of heparin to ASA therapy in a 64 YO male with coronary artery disease and unstable angina reduce mortality or the risk of MI?

CLINICAL BOTTOM LINE

  1. Treatment of unstable angina with combined ASA and heparin reduces the risk of MI or death compared with aspirin alone that is not statistically significant at the p<0.05 level.
  2. The NNT is 40 (22 - 59) to prevent one episode of MI or death.

THE EVIDENCE

MI or Death Ischemia Bleeding Revascular- ization MI or death 12 months after discontinuation
Relative Risk (95% CI) 0.67 (0.44-1.02) 0.68 (0.40-1.17) 1.89 (0.66-5.38) 1.03 (0.84-1.43) 0.82 (0.56-1.20)
NNT NA NA NA NA NA

COMMENTS:

  1. This meta-analysis was valid according to the JAMA Users' guide, however, included articles, although assessed for reviewer reproducibility, were not "weighted" according to the strength of the individual article when combining the results for the pooled RR's.
  2. The upper limit of the confidence interval for their point estimate of 0.67 was 1.02, including 1 as a possible relative risk. Their may be a trend toward statistical significance here, but one cannot say with a greater than 95% certainty that the addition of heparin significantly alters outcome, despite being able to calculate a NNT of 40 (range 22 -59).
  3. There was no overall evidence of heterogeneity among studies.
  4. Stroke may have been another clinically important outcome to look at, which was not done in this study.
  5. One might wonder why the authors decided to combine risk of MI and death together in the analysis. The raw data about these risks from each study was not provided, and therefore this author cannot perform the necessary re-calculations. However, I can say that it may be (by statistically combining these two end-points) the only way to show a trend toward statistical significance, especially since the results of this study fail to show any benefit of combined therapy versus aspirin alone for everything else other than combined risk of mortality and MI.
  6. However, based on these results, since the rate of bleeding is not significantly greater, one could argue that the potential small increase in benefit by adding heparin to aspirin may be worth the additional cost. Perhaps a large RCT with significant power could answer the question sufficiently.

APPRAISED BY:Patrick J. Sousa, MD

DATE:September 16, 1996

Oler A, et al. Adding Heparin to Aspirin Reduces the Incidence of Myocardial Infarction and death in Patients With Unstable Angina. JAMA1996;276:811- 815.