Treatment Discontinuations With New Oral Agents for Long-term Anticoagulation: Insights From a Meta-analysis of 18 Randomized Trials Including 101,801 Patients |
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| Institution: | 1. St Luke''s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, NY;2. Division of Cardiology, Texas Tech University Health Sciences Center, El Paso, TX;3. Division of Cardiology, University of Pennsylvania, Philadelphia;4. Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, NY;1. Department of Medicine and Cardiology, The Wright Center for Graduate Medical Center, Scranton, Pennsylvania;2. Department of Cardiology, Seth N.H.L. Municipal Medical College, Ahmedabad, India;3. Department of Cardiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania;1. Department of Internal Medicine, Hurley Medical Center/Michigan State University, Flint, MI 48503, United States;2. Division of Hematology & Oncology, Ascension St. John Hospital, Grosse Pointe Woods, MI 48236, United States;3. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, United States;4. Advanced Cancer Research Group, and University of Washington, Seattle, WA 98109, United States;5. Hutchinson Institute for Cancer Outcomes Research, Public Health Sciences and Clinical Research Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States;1. Department of Cardiology, Texas Tech University Health Sciences Center, El Paso, Texas, USA;2. Department of Cardiovascular Diseases, St Luke''s-Roosevelt Hospital of the Mount Sinai Health System, New York, New York, USA;3. Department of Cardiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA;4. Department of Cardiovascular Diseases, The Cardiovascular Institute, Mount Sinai Medical Center, New York, New York, USA |
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| Abstract: | ObjectiveTo systematically examine discontinuation rates with new US Food and Drug Administration–approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.Patients and MethodsPoor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.ResultsEighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.ConclusionStudy drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs. |
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