A Cost-Effectiveness Analysis of Combination Antiplatelet Therapy for High-Risk Acute Coronary Syndromes: Clopidogrel plus Aspirin versus Aspirin Alone

15 February 2005 | Volume 142 Issue 4 | Pages 251-259

Background: Although clopidogrel plus aspirin is more effective than aspirin alone in preventing subsequent vascular events in patients with unstable angina, the cost-effectiveness of this combination has yet to be examined in this high-risk population.

Objective: To determine the cost-effectiveness of clopidogrel plus aspirin compared with aspirin alone.

Design: Cost–utility analysis.

Data Sources: Published literature.

Target Population: Patients with unstable angina and electrocardiographic changes or non–Q-wave myocardial infarction.

Time Horizon: Lifetime.

Perspective: Societal.

Interventions: Combination therapy with clopidogrel, 75 mg/d, plus aspirin, 325 mg/d, for 1 year, followed by aspirin monotherapy, was compared with lifelong aspirin therapy, 325 mg/d.

Outcome Measures: Lifetime costs, life expectancy in quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio.

Results of Base-Case Analysis: Patients treated with aspirin alone lived 9.51 QALYs after their initial event and incurred expenses of $127 700; the addition of clopidogrel increased life expectancy to 9.61 QALYs and costs to $129 300. The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was $15 400 per QALY.

Results of Sensitivity Analyses: The analysis of 1 year of therapy was robust to all sensitivity analyses. In the probabilistic sensitivity analysis, fewer than 3% of simulations resulted in cost-effectiveness ratios over $50 000 per QALY. The cost-effectiveness of longer combination therapy depends critically on the balance of thrombotic event rates, durable efficacy, and the increased bleeding rate in patients taking clopidogrel.

Limitations: This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy, those recently managed with revascularization, or those undergoing short-term treatment with glycoprotein IIb/IIIa inhibitors.

Conclusions: In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits of cost-effectiveness. The durable efficacy of clopidogrel relative to the risk for hemorrhage should be further explored before more protracted therapy can be recommended.

Editors' Notes Context In patients with unstable angina, combination therapy with clopidogrel plus aspirin has been shown to be more effective than aspirin alone in preventing myocardial infarction, stroke, or cardiovascular death, but the cost-effectiveness of such therapy has yet to be determined. Contribution When the authors used a societal perspective and lifetime time horizon, combination therapy increased quality-adjusted life span at a cost that was within the traditionally accepted limits of cost-effectiveness. Cautions Data are not yet available to determine whether combination therapy for longer than 1 year remains cost-effective, due to the uncertainty of the relationship between long-term efficacy and risk for hemorrhage. –The Editors

 

Author and Article Information

From Brown University and Rhode Island Hospital, Providence, Rhode Island; and Stanford University Medical Center and VA Palo Alto Healthcare System, Palo Alto, California.

Grant Support: Dr. Schleinitz was supported in part by a Building Interdisciplinary Research Careers in Women's Health (BIRCWH) career development grant (HD43447) from the National Institutes of Health Office of Research on Women's Health, administered through Women and Infants' Hospital, Providence, Rhode Island. Dr. Heidenreich was supported by a Career Development Award from the Veterans Administration Health Services Research and Development Service (CD98326).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Mark D. Schleinitz, MD, MS, Division of General Internal Medicine, Brown University and Rhode Island Hospital, 593 Eddy Street, MPB-1, Providence, RI 02903; e-mail, Mark_Schleinitz{at}Brown.edu.

Current Author Addresses: Dr. Schleinitz: Brown University and Rhode Island Hospital, Division of General Internal Medicine, 593 Eddy Street, MPB-1, Providence, RI 02903.

Dr. Heidenreich: VA Palo Alto Healthcare System, 3801 Miranda Avenue, Palo Alto, CA 94304.

Author Contributions: Conception and design: M.D. Schleinitz, P.A. Heidenreich.

Analysis and interpretation of the data: M.D. Schleinitz, P.A. Heidenreich.

Drafting of the article: M.D. Schleinitz.

Critical revision of the article for important intellectual content: M.D. Schleinitz, P.A. Heidenreich.

Final approval of the article: M.D. Schleinitz, P.A. Heidenreich.

Statistical expertise: M.D. Schleinitz.

Collection and assembly of data: M.D. Schleinitz.

Read all Rapid Responses

Clopidogrel plus Aspirin. Can the Cost-Effectiveness Improve?

Enrique J. Sánchez-Delgado

Annals Online, 28 Feb 2005 [Full text]

Cost-Effectiveness of Extended Clopidogrel Therapy for High-Risk Acute Coronary Syndrome ? Some Addi

Peter Eriksson

Annals Online, 2 Mar 2005 [Full text]

Effectiveness assumption could overestimate the cost-effectiveness of clopidogrel

Michael B Rothberg

Annals Online, 15 Mar 2005 [Full text]

Authors' Response

Mark D. Schleinitz, et al.

Annals Online, 15 Apr 2005 [Full text]