Antithrombotic treatment and major adverse cardiac events after bleeding in patients with myocardial infarction: a retrospective analysis of nationwide registry data.

AIMS The aim of this study was to describe the use of antithrombotic therapy following a bleeding event among patients with myocardial infarction (MI), and the associated risk of major adverse cardiac events (MACE). METHODS AND RESULTS Using Danish nationwide registries patients hospitalized with a bleeding event within 1 year after MI were identified. Antithrombotic treatment with aspirin, clopidogrel and/or vitamin K antagonists (VKA) was determined at the bleeding and at Day 90 and 180 post bleed. Based on guidelines, patients were stratified into four groups: expected, reduced, discontinued, or intensified treatment. Risk of MACE (ischemic stroke, MI, or death) within the first year was assessed by Cox proportional hazard models. A total of 3324 patients with a bleeding after MI were included. At day 90 post bleed 1052 (31.7%) received expected antitrombotic treatment, 1301 (39.2%) reduced, 164 (4.9%) intensified, and 807 (24.3%) no treatment. MACE occurred in 637 (19.2%) patients. With dual antiplatelet therapy (DAPT) as reference, adjusted hazard ratios for MACE were: aspirin 1.81 (1.06-3.09), clopidogrel 1.08 (0.64-1.82), VKA 1.08 (0.47-2.48), VKA+aspirin 1.97 (0.95- 4.07), VKA+clopidogrel 0.26 (0.03-1.91), triple 1.73 (0.50-5.95), no treatment 1.93 (1.11-3.36). CONCLUSIONS The majority of MI patients reduced or discontinued their antithrombotic therapy post-bleed. Patients in monotherapy with aspirin or no treatment post-bleed had a higher risk of MACE Further studies of optimal antithrombotic treatments after a bleed are needed.

[1]  G. Specchia,et al.  Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. , 2002, European heart journal.

[2]  S. Yusuf,et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. , 2001, The New England journal of medicine.

[3]  P. Kirchhof,et al.  2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. , 2016, European heart journal.

[4]  S. Yusuf,et al.  Adverse Impact of Bleeding on Prognosis in Patients With Acute Coronary Syndromes , 2006, Circulation.

[5]  Sunil V. Rao,et al.  Bleeding as a predictor of mortality risk. , 2006, Reviews in cardiovascular medicine.

[6]  Seung‐Jung Park,et al.  Impact of in‐hospital bleeding according to the bleeding academic research consortium classification on the long‐term adverse outcomes in patients undergoing percutaneous coronary intervention , 2015, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[7]  J. Tu,et al.  Cardiovascular outcomes after a change in prescription policy for clopidogrel. , 2008, The New England journal of medicine.

[8]  K. Helweg-larsen.  The Danish Register of Causes of Death , 2011, Scandinavian journal of public health.

[9]  T. Gerds,et al.  Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study , 2018, European heart journal.

[10]  P. Kirchhof,et al.  2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. , 2016, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[11]  L. Pilote,et al.  Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. , 2005, Archives of internal medicine.

[12]  G. Stone,et al.  [Percutaneous coronary interventions. Guidelines of the European Society of Cardiology-ESC]. , 2005, Kardiologia polska.

[13]  Antonio Colombo,et al.  Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study , 2013, The Lancet.

[14]  L. Køber,et al.  Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data , 2009, The Lancet.

[15]  S. Steinhubl,et al.  Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis. , 2008, Journal of the American College of Cardiology.

[16]  J V Tu,et al.  Development and validation of the Ontario acute myocardial infarction mortality prediction rules. , 2001, Journal of the American College of Cardiology.

[17]  L. Newby,et al.  Patterns of discharge antiplatelet therapy and late outcomes among 8,582 patients with bleeding during acute coronary syndrome: a pooled analysis from PURSUIT, PARAGON-A, PARAGON-B, and SYNERGY. , 2010, American Heart Journal.

[18]  G. Lip,et al.  Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting. , 2008, Chest.

[19]  Samy Suissa,et al.  Immortal time bias in pharmaco-epidemiology. , 2008, American journal of epidemiology.

[20]  M. LeWinter,et al.  Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. , 1983, The New England journal of medicine.

[21]  G. Lip,et al.  Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis , 2016, European heart journal.

[22]  Sunil V. Rao,et al.  The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction. , 2012, European heart journal.

[23]  L. Køber,et al.  Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. , 2006, European heart journal.

[24]  Jeroen J. Bax,et al.  ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation , 2012 .

[25]  A. Vaag,et al.  Risk of cancer in patients using glucose-lowering agents: a nationwide cohort study of 3.6 million people , 2012, BMJ Open.

[26]  P. Kirchhof,et al.  2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. , 2016, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[27]  Sunil V. Rao,et al.  Antiplatelet Therapy Use After Discharge Among Acute Myocardial Infarction Patients With In-Hospital Bleeding , 2008, Circulation.

[28]  G. Lemesle,et al.  Impact of "nuisance" bleeding on clopidogrel compliance in patients undergoing intracoronary drug-eluting stent implantation. , 2008, The American journal of cardiology.

[29]  S. Yusuf,et al.  Improving clinical outcomes by reducing bleeding in patients with non-ST-elevation acute coronary syndromes. , 2008, European heart journal.

[30]  Jeroen J. Bax,et al.  2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). , 2011, European heart journal.

[31]  R. Califf,et al.  Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. , 2005, The American journal of cardiology.

[32]  William Wijns,et al.  [Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes]. , 2007, Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.

[33]  T. Lauer,et al.  Kardiologische Aspekte der präoperativen Risikostratifizierung , 2011 .

[34]  S. Werns.  Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes , 2011 .

[35]  Sunil V. Rao,et al.  Baseline Risk of Major Bleeding in Non–ST-Segment–Elevation Myocardial Infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Bleeding Score , 2009, Circulation.

[36]  S. Yusuf,et al.  Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. , 2010, The New England journal of medicine.

[37]  K. Kent,et al.  Incidence, correlates, and clinical impact of nuisance bleeding after antiplatelet therapy for patients with drug-eluting stents. , 2010, American heart journal.