Author + information
- Peter Eriksson, MD, PhD⁎ ()
- ↵⁎Interventional Cardiology Laboratory, Heart Center, University Hospital, SE-901 85 Umea, Sweden
In the February 1 issue of the Journal, Cowper et al. (1) compared the outcomes and costs of extending clopidogrel therapy (in addition to aspirin) from one month to one year after percutaneous coronary intervention (PCI), with withdrawal of clopidogrel after one month. Unpublished per-protocol data from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial (2) were used to estimate the effects of long-term clopidogrel use on event rates in a sample of patients at the Duke Medical Center undergoing PCI and receiving clopidogrel for only one month after the procedure. The investigators concluded that clopidogrel therapy for one year after PCI is economically attractive in respect to cost per year of life saved, particularly in high-risk patients.
However, the conclusions of Cowper et al. (1) rest solely on the assumption that clopidogrel between one month and one year after PCI significantly reduces the incidence of myocardial infarction (MI). The relative risk (RR) of MI was estimated to be 0.56 with clopidogrel long-term, but the 95% confidence interval (CI) was 0.3 to 1.0, suggesting a possibility of no effect at all. Consequently, the costs per year of life saved may actually be unlimited, as shown in Figure 2 in the study by Cowper et al. (1). Moreover, by using per-protocol rather than intent-to-treat data, an even distribution of confounders produced by randomization was altered, which may have incorrectly favored extended clopidogrel therapy. In fact, the one-year intention-to-treat analysis of the CREDO trial did not show a significant reduction of MI between day 0 and one year or between one month and one year (RR reduction between day 0 to one year, 21.7%; 95% CI −7.1% to 42.7%) (2,3). Similarly, the observational PCI substudy of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial (4) did not show an advantage of long-term clopidogrel use over placebo in terms of death or MI beyond 30 days after PCI (RR reduction 23%; 95% CI, −17% to 50%) (5).
An increase of major bleeding occurs when clopidogrel is added to aspirin long-term (2,6,7), and bleeding (like MIs) may influence prognosis adversely (8). Only the costs of bleeding, but not a potential negative effect on life expectancy, were incorporated into the model used by Cowper et al. (1). In addition, the low compliance with therapy in the CREDO trial (∼60%) may have obscured the true risk of severe bleedings with dual antiplatelet therapy.
Finally, the conclusions of Cowper et al. (1) should be viewed with caution—they seem overenthusiastic and may be incorrect. Health economics cannot help to guide decisions on therapy when there is no firm evidence of clinical efficacy. Combining clopidogrel and aspirin long-term may actually do more harm than good.
- American College of Cardiology Foundation
- Cowper P.A.,
- Udayakumar K.,
- Sketch M.H. Jr.,
- Peterson E.D.
- Eriksson P.