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Cost-Effectiveness of Clopidogrel plus Aspirin versus Aspirin Alone
- Mark D. Schleinitz, MD, MS; and
- Paul A. Heidenreich, MD, MS
- From Brown University, Providence, RI 02903, and VA Palo Alto Healthcare System, Palo Alto, CA 94304.
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IN RESPONSE:
Dr. Rothberg suggests that our analysis would have been stronger if we had used outcome-specific estimates of the efficacy of clopidogrel when added to aspirin. We agree in theory and have used this approach in an analysis of clopidogrel monotherapy (1). The CURE trial (2), however, did not report the numbers of each type of event that made up the composite outcomes. The cardiovascular death rate cited by Rothberg, for example, is itself a composite of deaths due to stroke, myocardial infarction, and other cardiovascular causes. We felt that the potential to introduce bias by estimating event rates for aspirin monotherapy as well as combination therapy and using these calculations to approximate outcome-specific efficacy was too great to justify this method.
Dr. Eriksson emphasizes our point that balancing protection from thrombotic events with the risk for hemorrhage is critical in determining the benefit of adding clopidogrel to aspirin, and thereby its cost-effectiveness. Assuming constant relative efficacy of combination therapy, we found that the diminishing absolute benefit in thrombotic event rates is negated by the constant risk for hemorrhage after 5 years.
Cost may help specify the “ideal” duration of therapy in 1 of 2 ways: at the average individual level, as reflected by the incremental cost-effectiveness ratio, or at the societal budgetary level, a function of both the incremental cost-effectiveness ratio and the size of the affected population. Variation in both societal preference and available resources means that this “ideal” duration may differ among countries.
Eriksson also notes that in a post hoc evaluation, the efficacy estimate of adding clopidogrel to aspirin varied with the dose of aspirin (3). Aspirin dose was determined at the physician's discretion. We have shown that efficacy estimates of antiplatelet therapies derived from nonrandomized studies may be statistically distinct from results of randomized comparisons (4), and we agree that a randomized comparison is warranted to clarify the optimal dose of aspirin for combination therapy.
Paul A. Heidenreich, MD, MS
VA Palo Alto Healthcare System
Palo Alto, CA 94304
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
Article and Author Information
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Potential Financial Conflicts of Interest: None disclosed.
