Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation
Archives of Internal MedicinePublished 13 September 2010
Morten Lock Hansen, Rikke Sørensen, Mette T. Clausen, Marie Louise Fog-Petersen, Jakob Raunsø, Niels Gadsbøll
Citations839
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding.
Abstract
In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
Keywords
Medicine
The LancetA randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)
6,453 Citations1996
Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death.
The LancetA randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee
2,732 Citations1996Martin Dennis
New England Journal of MedicineEffect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation
2,098 Citations2009Stuart J. Connolly
In patients with atrial fibrillation for whom vitamin K-antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the riskof major hemorrhage.
The LancetClopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial
1,962 Citations2006‡
Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoAGulation therapy.
The LancetPLACEBO-CONTROLLED, RANDOMISED TRIAL OF WARFARIN AND ASPIRIN FOR PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN CHRONIC ATRIAL FIBRILLATION
1,826 Citations1989Palle Petersen, J Godtfredsen +3 more
The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly.
CirculationStroke Prevention in Atrial Fibrillation Study. Final results.
1,712 Citations1991
Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation and patients with nonrheumatic atrialfibrillation who can safely take either aspirin or warfarIn should receive prophylactic antithrombotic therapy to reduce the risk of stroke.
The LancetWarfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial
1,558 Citations2007Jonathan Mant, Richard Hobbs +5 more
These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.
New England Journal of MedicineThe Effect of Low-Dose Warfarin on the Risk of Stroke in Patients with Nonrheumatic Atrial Fibrillation
1,535 Citations1990Daniel E. Singer
Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring.
Journal of the American College of CardiologyACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—Executive Summary
1,167 Citations2006Valentı́n Fuster, Lars Rydén +12 more
Journal of the American College of CardiologyCanadian atrial fibrillation anticoaguiation (CAFA) study
1,119 Citations1991Stuart J. Connolly, Andreas Laupacis +4 more
The LancetAdjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial
1,095 Citations1996
Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-doseWarfarin (target INR 2.0-3.0) importantly reduces stroke for high- risk patients.
CirculationMajor Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation
1,064 Citations2007Elaine M. Hylek, Carmella Evans‐Molina +3 more
Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice, and this finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization.
Annals of Internal MedicineRisk Factors for Intracranial Hemorrhage in Outpatients Taking Warfarin
920 Citations1994Elaine M. Hylek, Daniel E. Singer
The results emphasize the importance of maintaining the prothrombin time ratios under 2.0 and the need for especially careful use of warfarin in the elderly.
CHEST JournalAntithrombotic Therapy in Atrial Fibrillation
755 Citations2008Daniel E. Singer, Gregory W. Albers +6 more
This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition).
JAMAOral Anticoagulants vs Aspirin in Nonvalvular Atrial Fibrillation
717 Citations2002Carl van Walraven, Robert G. Hart +7 more
Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding.
Annals of Internal MedicineRisk Factors for Complications of Chronic Anticoagulation: A Multicenter Study
671 Citations1993Stephan D. Fihn, Mary McDonell +6 more
The incidence of bleeding and thromboembolic complications and related risk factors from a retrospective study of 980 patients followed in five anticoagulation clinics through 1990 are described.
European Heart JournalACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary
646 Citations2006Authors/Task Force Members, Valentı́n Fuster +40 more
Patients With Atrial Fibrillation—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiological Committee for Practice Guidelines developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.
The LancetRisk 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
570 Citations2009Rikke Sørensen, Morten Lock Hansen +9 more
In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used, and treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment.
PubMedThe Danish prescription registries.
570 Citations1997David Gaist, Henrik Toft Sørensen +1 more
The degree of completeness of the Danish prescription registries is excellent for reimbursed prescription drugs and a small number of comparison studies also indicate high validity of the register information.
Annals of Internal MedicineMeta-analysis: Anticoagulant Prophylaxis to Prevent Symptomatic Venous Thromboembolism in Hospitalized Medical Patients
539 Citations2007Francesco Dentali, James D. Douketis +3 more
A meta-analysis of randomized, controlled trials of anticoagulant prophylaxis in medical patients, focusing on the effects of treatment on clinically important efficacy outcomes (any PE, fatal PE, symptomatic DVT, and all-cause mortality) and safety outcomes (major bleeding).
Archives of Internal MedicineFixed Minidose Warfarin and Aspirin Alone and in Combination vs Adjusted-Dose Warfarin for Stroke Prevention in Atrial Fibrillation
300 Citations1998Annette Lemche Gulløv, Birgitte Gade Koefoed +5 more
The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.
European Heart JournalLong-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction
300 Citations2006Gunnar Gislason, Jeppe Nørgaard Rasmussen +9 more
A focused effort in the immediate post-infarction period would appear to provide long-term benefit in patients after acute myocardial infarction and likely targets for improvement are identified.
European Heart JournalSafety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting
288 Citations2007Pasi P. Karjalainen, Pekka Porela +8 more
It is shown that the prognosis is unsatisfactory in warfarin-treated patients irrespective of the drug combination used, and aspirin plus Warfarin combination seems to be inadequate to prevent stent thrombosis.
Journal of the American College of CardiologyAnticoagulant and Antiplatelet Therapy Use in 426 Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention and Stent Implantation
269 Citations2008Juan M. Ruiz-Nodar, Francisco Marı́n +8 more
Patients with AF undergoing PCI with stenting represent a high-risk population because of age, comorbidities, and presence of stroke risk factors and have a high mortality and MACE rate, which is reduced by anticoagulation therapy.
CirculationAlcohol Consumption and Risk of Atrial Fibrillation in Men and Women
266 Citations2005Kenneth J. Mukamal, Janne Schurmann Tolstrup +3 more
Heavy alcohol consumption is associated with a higher risk of atrial fibrillation, at least among men, and this relationship does not appear to be related to the adverse effects of heavy drinking on coronary heart disease or blood pressure.
StrokeCombined Anticoagulant–Antiplatelet Use and Major Bleeding Events in Elderly Atrial Fibrillation Patients
230 Citations2004Theresa I. Shireman, Patricia Howard +2 more
PubMedCombination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding.
185 Citations2006Zakaria Khurram, Eric T. Chou +6 more
In patients requiring warfarin therapy, the addition of dual antiplatelet therapy is associated with an approximately 7% major bleeding risk, and novel regimens are needed to reduce the bleeding risk.
American Heart JournalRisks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: An exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials
182 Citations2006Greg C. Flaker, Michael J. Gruber +7 more
The results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit and that the benefits of aspirin combined with warfarin or ximelagatran outweigh the risks.
Thrombosis ResearchOptimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal
164 Citations2004Anders Odén, Martin Fahlén +1 more
It is concluded that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.
Pharmacoepidemiology and Drug SafetyThe pattern of use of non‐steroidal anti‐inflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people
143 Citations2008Emil Loldrup Fosbøl, Gunnar Gislason +10 more
To describe the nationwide pattern of use of non‐steroidal anti‐inflammatory drugs (NSAIDs) in the Danish population, a large number of NSAIDs are prescribed to the general population.
Annals of MedicineAntithrombotic therapy in patients treated with oral anticoagulation undergoing coronary artery stenting. An expert consensus document with focus on atrial fibrillation
125 Citations2008Andrea Rubboli, Jonathan L. Halperin +9 more
It is acknowledged that the optimal antithrombotic treatment for patients with AF at medium or high thromboembolic risk undergoing PCI-S is currently undefined, triple therapy of warfarin, aspirin, and clopidogrel is currently recommended, although associated with an increased risk of major bleeding.
CHEST JournalIncreased Major Bleeding Complications Related to Triple Antithrombotic Therapy Usage in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Artery Stenting
122 Citations2008Sergio Manzano‐Fernández, Juan Francisco Pastor +8 more
A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.
European Heart JournalCombining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent?
121 Citations2007M.C. Nguyen, Yu Liang Lim +9 more
There was no difference in mortality or myocardial infarction at 6 months in the single vs. dual antiplatelet group and larger trials are needed to assert any firm recommendations.
Journal of Internal MedicineMajor haemorrhagic complications during oral anticoagulant therapy in a Danish Population‐based cohort
104 Citations1997Flemming Hald Steffensen, Kurt Kristensen +3 more
Major haemorrhagic complications during oral anticoagulant therapy in a Danish population‐based cohort is found to be a major cause of death in these patients.
JACC: Cardiovascular InterventionsDual Antiplatelet Therapy After Percutaneous Coronary Intervention With Stent Implantation in Patients Taking Chronic Oral Anticoagulation
97 Citations2008Renata Rogacka, Alaide Chieffo +13 more
The purpose of this study was to evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation with warfarin is recommended, and to identify the optimal antithrombotic strategy after percutaneous coronary intervention for patients receiving AC.
Pharmacotherapy The Journal of Human Pharmacology and Drug TherapyRisk of Major Bleeding with Concomitant Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients Receiving Long‐Term Warfarin Therapy
93 Citations2007Deborah DeEugenio, Louis Kolman +11 more
The safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention is characterized and patient characteristics that increase the risk of hemorrhage are identified.
Journal of Internal MedicineAspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation
85 Citations2008Nikolaus Sarafoff, Gjin Ndrepepa +7 more
This work investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC.
CHEST JournalOutcomes Associated With Combined Antiplatelet and Anticoagulant Therapy
81 Citations2008Samuel G. Johnson, Kristina Rogers +2 more
The findings suggest that clinicians should carefully consider the risks and benefits when recommending combined antiplatelet therapy for patients receiving warfarin who do not meet the evidence-based criteria for such therapy.
British Journal of Clinical PharmacologyUse of sumatriptan in Denmark in 1994–5: an epidemiological analysisof nationwide prescription data
53 Citations1997David Gaist, Morten Andersen +3 more
It is concluded that sumatriptan had a considerable impact on the treatment of migraine with prescription drugs in Denmark and the underlying reasons for high use of the drug in a smaller fraction of the patients deserve further study.
Medical CareHospital Variation in Mortality After First Acute Myocardial Infarction in Denmark From 1995 to 2002
50 Citations2005Søren Rasmussen, Ann‐Dorthe Zwisler +3 more
Type of hospital, and especially total MI volume at the hospital level, were significantly associated with mortality after AMI, and individual hospitals varied substantially in both short- and long-term mortality.
NeuroepidemiologyTrends in Risk of Stroke in Patients with a Hospital Diagnosis of Nonvalvular Atrial Fibrillation: National Cohort Study in Denmark, 1980–2002
37 Citations2006Lars Frost, Ljubica Vukelic Andersen +3 more
A modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980–2002 is observed, however, the authors could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrium fibrillillation.
Seminars in Arthritis and RheumatismGastroduodenal mucosal damage with salsalate versus aspirin: Results of experimental models and endoscopic studies in humans
32 Citations1990James M. Scheiman, Grace H. Elta
Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans and an endoscopic study in rheumatoid arthritics confirmed the ability of salsalates to spare gastroduODenal mucosa when compared to naproxen administration.
EP EuropaceAtrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers
24 Citations2008Morten Lock Hansen, Niels Gadsbøll +11 more
Pharmacotherapy of atrial fibrillation has changed towards increased beta-blocker use with a coincident decrease in the use of other rate-limiting drugs and sotalol and oral anticoagulant therapy increased considerably, but women and elderly were apparently undertreated.