| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Jaspers Focks, Jeroen Brouwer, Marc A. Thomas, Laine Verheugt, Freek W. A. Washam, Jeffrey B. Wojdyla, Daniel M. Lanas, Fernando Alexander, John H. Granger, Christopher B. Wallentin, Lars Husted, Steen Lopes, Renato D. Xavier, Denis |
| Description |
Author Affiliation: Jaspers Focks J ( Department of Cardiology, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB Nijmegen, Netherlands Jeroen.Jaspersfocks@radboudumc.nl.); Brouwer MA ( Department of Cardiology, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB Nijmegen, Netherlands.); Wojdyla DM ( Duke Clinical Research Institute, Durham, NC, USA.); Thomas L ( Duke Clinical Research Institute, Durham, NC, USA.); Lopes RD ( Duke Clinical Research Institute, Durham, NC, USA.); Washam JB ( Duke Heart Center, Duke University Medical Center, Durham, NC, USA.); Lanas F ( Department of Cardiology, Universidad de La Frontera, Temuco, Chile.); Xavier D ( Department of Pharmacology and Clinical Research, St John's Medical College and Research Institute, Bangalore, India.); Husted S ( Department of Medicine, Hospital Unit West, Herning, Denmark.); Wallentin L ( Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Upsala University, Uppsala, Sweden.); Alexander JH ( Duke Clinical Research Institute, Durham, NC, USA.); Granger CB ( Duke Clinical Research Institute, Durham, NC, USA.); Verheugt FW ( Department of Cardiology, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB Nijmegen, Netherlands.); |
| Abstract |
Objective To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation. Design Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)—a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011. Participants 18 201 ARISTOTLE trial participants. Interventions In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years. Main outcome measures Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country). Results Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs $(P_{interaction}=0.82).$ A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs $(P_{interaction}=0.017).$ Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin. Conclusions In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe. Trial registration ARISTOTLE trial, ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00412984","term_id":"NCT00412984"}}NCT00412984. |
| ISSN |
09598138 |
| e-ISSN |
17561833 |
| Journal |
BMJ (British Medical Journal) |
| Volume Number |
353 |
| Language |
English |
| Publisher |
British Medical Journal Publishing Group |
| Publisher Date |
2016-06-01 |
| Publisher Place |
Great Britain (UK) |
| Access Restriction |
Open |
| Subject Keyword |
Medicine |
| Content Type |
Text |
| Resource Type |
Article |
