title: Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study.
abstract: BACKGROUND
  Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown.
  
  
  METHODS
  The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events.
  
  
  RESULTS
  Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P=0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29-0.58; P<0.001; interaction P=0.103). Comparing continued thienopyridine versus placebo, rates of major adverse cardiovascular and cerebrovascular events were 4.2% versus 5.0% among patients on OMT (HR, 0.82; CI, 0.66-1.02; P=0.077) and 4.5% versus 7.0% among those off OMT (HR, 0.63; CI, 0.49-0.82; P<0.001; interaction P=0.250); rates of bleeding for thienopyridine versus placebo in patients on OMT were 2.2% versus 1.0% (HR, 2.13; CI, 1.43-3.17; P<0.001), and in patients off OMT were 2.8% versus 2.2% (HR, 1.30; CI, 0.88-1.92; P=0.189; interaction P=0.073). Overall, patients on OMT had lower rates of myocardial infarction (2.7% versus 3.7%, P=0.003), major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%, P=0.007), and bleeding (1.6% versus 2.5%, P<0.001) in comparison with patients off OMT. Rates of stent thrombosis (0.8% versus 1.0%, P=0.171) and death (1.6% versus 1.9%, P=0.155) did not differ.
  
  
  CONCLUSIONS
  Continued thienopyridine therapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov. Unique identifier: NCT00977938.
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Charles D
authors: CD
authors: Resor
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Ashwin
authors: A
authors: Nathan
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Dean J
authors: DJ
authors: Kereiakes
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Robert W
authors: RW
authors: Yeh
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Joseph M
authors: JM
authors: Massaro
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Donald E
authors: DE
authors: Cutlip
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: P
authors: P
authors: Gabriel Steg
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.).
authors: Wen-Hua
authors: WH
authors: Hsieh
authors: From Division of Cardiology and Center for Clinical Biometrics, Department of Medicine, Brigham and Women's Hospital, Boston, MA (C.D.R., L.M.); Harvard Clinical Research Institute, Boston, MA (R.W.Y., D.E.C., W.-H.H., L.M.); Harvard Medical School, Boston, MA (R.W.Y., L.M.); Division of Cardiology, University of Pennsylvania Medical Center, Philadelphia (A.N.); Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (R.W.Y., D.E.C.); Department of Biostatistics, Boston University School of Public Heath, MA (J.M.M.); The Christ Hospital Heart and Vascular Center and The Lindner Center for Research and Education, Cincinnati, OH (D.J.K.); Université Paris-Diderot, INSERM U-1148, Hôpital Bichat, Département Hospitalo-Universitaire Fibrosis, Inflammation, and Remodeling, Assistance Publique-Hôpitaux de Paris, Paris, France (P.G.S.); and National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, UK (P.G.S.). lmauri1@partners.org.
authors: Laura
authors: L
authors: Mauri
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D062645:Percutaneous Coronary Intervention / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
keywords: antiplatelet agents; medical therapy; stents