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Role of Dual Antiplatelet Therapy in Symptomatic Patients with Established Vascular Disease: Putting the CHARISMA Trial into Therapeutic Perspective

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Abstract

Introduction

The CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial has spurred debate over subgroup analysis interpretation and prompted renewed consideration of the long-term role of dual aspirin and clopidogrel therapy (DAPT) in patients with established vascular disease.

Discussion

Previous DAPT studies consistently demonstrated greater efficacy but an increased risk of bleeding compared with aspirin alone in patients with acute coronary syndromes or undergoing percutaneous coronary intervention. However, CHARISMA data were inconclusive and difficult to interpret. The principal subgroup analysis showed a significant benefit for clopidogrel plus aspirin in the 80% of patients with documented vascular disease, but unexpectedly showed potential harm in the ∼20% of asymptomatic patients.

Conclusions

Hypothesizing that dual antiplatelet therapy would provide benefit across the broad spectrum of atherothrombotic disease was plausible. In retrospect, it is apparent that by combining such a heterogeneous population, CHARISMA failed to show a clear treatment effect for DAPT and potentially masked important benefits in specific populations. Given the inherent clinical and biological variability among patients and disease states, difficult-to-interpret clinical data should not be dismissed. The current challenge is identifying clinically useful data from CHARISMA to determine the role of DAPT in contemporary clinical practice.

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Acknowledgments

Professional editorial assistance with searching the literature, creating tables, ensuring language accuracy, coordinating revisions, and ensuring version control in preparation of this manuscript was provided by Susan Abulhawa, Melanie Leiby, PhD, and Barbara Murphy of inScience Communications, part of the Wolters Kluwer organization.

The editorial assistance was funded by the Bristol-Myers Squibb (New York, NY)/Sanofi Pharmaceuticals (Paris, France) Partnership and performed in compliance with the good publishing practices outlined by the International Committee of Medical Journal Editors. The authors, who did not receive compensation for this work, had complete control of the writing and editing process and take full responsibility for all content.

Individual author disclosures

Dr. Bhatt has received research grants (to the institution) from: AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, sanofi-aventis, and The Medicines Company. He served as the international primary investigator of the CHARISMA trial, which was funded by sanofi-aventis and Bristol-Myers Squibb.

Dr. Flather has received institutional research grants from sanofi-aventis and Bristol-Myers Squibb and honoraria for speaker meetings. He was also an investigator in the CHARISMA trial, which was funded by sanofi-aventis and Bristol-Myers Squibb. He has also received institutional research grants from GlaxoSmithKline and Actelion, honoraria for speaker meetings and advisory panels from Eli Lilly & Co., Pfizer, and Daiichi Sankyo, Inc., and holds a consultancy contract with Eisai.

Dr. Boden has served as a consultant or received consulting fees or honoraria from Abbott Laboratories, Bristol-Myers Squibb, CV Therapeutics, Merck, PDL BioPharma, Pfizer, and sanofi-aventis.

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Authors and Affiliations

  1. Buffalo General Hospital and SUNY, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA

    William E. Boden

  2. Clinical Trials and Evaluation Unit, Royal Brompton Hospital and Imperial College, London, UK

    Marcus D. Flather

  3. VA Boston Healthcare System and Brigham and Women’s Hospital, Boston, MA, USA

    Deepak L. Bhatt

  4. Division of Cardiology, Buffalo General Hospital, SUNY at Buffalo School of Medicine, 100 High Street, Buffalo, NY, 14203, USA

    William E. Boden

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  1. William E. Boden
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Correspondence to William E. Boden.

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Boden, W.E., Flather, M.D. & Bhatt, D.L. Role of Dual Antiplatelet Therapy in Symptomatic Patients with Established Vascular Disease: Putting the CHARISMA Trial into Therapeutic Perspective. Cardiovasc Drugs Ther 24, 207–216 (2010). https://doi.org/10.1007/s10557-010-6245-9

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