title: Role of dual antiplatelet therapy in symptomatic patients with established vascular disease: putting the CHARISMA trial into therapeutic perspective.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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 approximately 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.
authors.affiliation: Buffalo General Hospital and SUNY, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA. wboden@kaleidahealth.org
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012189:Retrospective Studies; D012306:Risk; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014652:Vascular Diseases / Q000188:drug therapy
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin