Apixaban more effective than warfarin regardless of polypharmacy

Researchers found new anticoagulant consistently reduced stroke, although benefits for major bleeding risk declined as number of medicines increased.

Blood clot illustration

The oral anticoagulant apixaban is consistently more effective than warfarin for patients with atrial fibrillation regardless of the number of other drugs they take, a study has found. 

Apixaban (Eliquis; Bristol-Myers Squibb) is a new oral anticoagulant used to reduce the risk of stroke. While studies have found it to be more effective and safer than warfarin, it has been unclear whether this was the case in patients taking many medications. 

Reporting their findings in The BMJ
(online, 20 June 2016), researchers re-analysed data from the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, where 18,201 patients were randomised to either apixaban or warfarin. Patients were split into one of three groups according to the number of medicines they took at baseline: 0–5 medicines, 6–8 medicines or ≥9 medicines. Polypharmacy was observed in 13,932 patients (76.5%), which is defined as taking more than five medicines. 

The authors discovered that, while apixaban consistently reduced the risk of stroke or systemic embolism compared to warfarin for all medication groups, the benefit of apixaban over warfarin with regards to major bleeding risk declined as the number of medicines increased. 

The absolute rate reduction of major bleeding per 100 patient years was 1.28, 0.82, and 0.66 for the three groups (0–5, 6–8, and ≥9 drugs, respectively). Interestingly, the researchers note that the decline in benefit did not seem to be the result of patients taking interacting medicines that enhance anticoagulation. 

The risk of death increased significantly with increasing medication burden (P<0.001) as did the risk of stroke and systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0–5, 6–8, and ≥9 drugs, respectively). The risk of major bleeding also increased with the number of medicines taken (1.91, 2.46, and 3.88 per 100 patient years, respectively). As expected, the researchers found that the more health conditions a patient had, the more medicines they were prescribed and they say that the increase in health risk must be placed in the context of the increasing burden of illnesses, not just an increasing number of medications. 

Source: Sharron Gordon

Sharron Gordon, a consultant pharmacist in coagulation, says the results should be used as an opportunity to minimise risks by stopping other medicines that may no longer be required

Commenting on the study, Sharron Gordon, consultant pharmacist in anticoagulation at the Hampshire Hospitals NHS Foundation Trust, says the results will come as no surprise to pharmacists, who are always aware of concomitant medicines, but that this should not detract from the need to anticoagulate patients. 

“This must be used as an opportunity to minimise risks by stopping other medicines that may no longer be required, particularly antiplatelets and other interacting or potentiating medicines,” she says. 

She warns drawing any firm conclusions from a post-hoc review is not recommended because the study was “not powered to generate these findings”. 

In addition, Gordon points out that the trial had a patient demographic of reasonably low-risk patients who had relatively low scores on an assessment of both stroke risk and major bleeding risk, plus average follow-up was only 1.8 years. “In real life situations these outcomes could be different,” she says. 

Of note in the multi-region trial, which involved patients from North and Latin America, Europe and Asia, was that patients in the United States and Canada were prescribed many more medicines than those in other regions: 53% of US patients and 38% of Canadian patients were taking nine or more medicines, compared with 10–21% in other regions. 

The researchers say that although patients in the United States had more comorbidities than those in other regions, a greater number of drugs were used in US patients regardless of comorbidities.


[1] Focks, JJ, Brouwer, MA, Wojdyla, DM, et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. The BMJ. 2016;353:i2868 doi: 10.1136/bmj.i2868

Last updated
The Pharmaceutical Journal, PJ, July 2016, Vol 297, No 7891;297(7891):DOI:10.1211/PJ.2016.20201348

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