ArticlesRisk 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
Introduction
Treatment with aspirin and clopidogrel is recommended after acute myocardial infarction to reduce recurrent ischaemic events.1, 2, 3 Some patients have an additional indication for treatment with a vitamin K antagonist.4 Treatment with multiple antithrombotic drugs after myocardial infarction represents a clinical dilemma because risk of bleeding is exacerbated with combination therapy and longer duration of treatment. Although several studies have reported rates of bleeding,5, 6, 7, 8, 9 research on antithrombotic drugs has generally focused on improving efficacy rather than safety. Additionally, the safety of several drug combinations has not been investigated in clinical trials. Guidelines for the management of patients with myocardial infarction who also have an indication for vitamin K antagonists are unclear.1, 2, 4, 10 Combination treatment is widely used and some guidelines recommend an untested combination of clopidogrel plus vitamin K antagonist as the preferred option for patients with myocardial infarction who are treated with an intracoronary stent.4, 10 Since bleeding episodes in patients with myocardial infarction are associated with increased morbidity and mortality,11, 12 the use of undocumented treatment combinations raises concerns.
We undertook a nationwide study of 40 812 unselected patients treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists after myocardial infarction to examine the risk of non-fatal and fatal bleeding in a real-life setting and to identify the safest combinations of antithrombotic drugs.
Section snippets
Study population
Four nationwide administrative registers were linked on an individual level and used in this study: (1) the Danish National Patient Register, which holds information about all admissions to Danish hospitals since 1978 with diagnoses coded according to the International Classification of Diseases (ICD)-8 and ICD-10; (2) the Danish Register of Medicinal Product Statistics (the national prescription register), which contains information about all prescriptions dispensed in Danish pharmacies since
Results
We identified 40 812 patients who were admitted to hospital with first-time myocardial infarction in Denmark during 2000–05, and who claimed a prescription of aspirin, clopidogrel, or a vitamin K antagonist within 90 days of hospital discharge. Table 1 shows the baseline characteristics of patients by first drug exposure group. See webappendix p 1 for baseline characteristics of patients according to PCI status. Several patients changed treatment regimen, and therefore drug exposure group,
Discussion
We examined the association between occurrence of non-fatal and fatal bleeding and treatment with combinations of aspirin, clopidogrel, and vitamin K antagonists in a nationwide cohort of patients with first-time myocardial infarction. All drug combinations were associated with an increased risk of hospital admission for non-fatal and fatal bleeding, apart from monotherapy with a vitamin K antagonist. Increased risk of bleeding was proportional to the number of drugs used. Notably, dual therapy
References (31)
- et al.
Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study
Lancet
(2001) - et al.
Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes
Am J Cardiol
(2005) - et al.
Development and validation of the Ontario acute myocardial infarction mortality prediction rules
J Am Coll Cardiol
(2001) - et al.
Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis
J Am Coll Cardiol
(2008) - et al.
Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting
Chest
(2008) - et al.
Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial
Lancet
(2002) - et al.
The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the Danish MONICA registry
J Clin Epidemiol
(2003) - et al.
ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
Circulation
(2007) - et al.
Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes
Eur Heart J
(2007) - et al.
Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology
Eur Heart J
(2005)