Combination therapy with warfarin, aspirin may increase bleeding complications
Combining aspirin with warfarin led to increased bleeding complications in patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE) compared with warfarin alone, resulting in higher rates of major bleeding events and hospital admissions, according to data presented at ASH 2017.
“Over one-third of patients in an unselected practice-based setting are treated with warfarin-[aspirin] for AF and/or VTE without a clear indication … [which] place[s] patients at increased bleeding risk,” said Dr Jordan Schaefer from the University of Michigan, Dexter, Michigan, US.
To evaluate the outcomes of warfarin-aspirin combination therapy, a retrospective study on 6,572 patients from the MAQI* Initiative was conducted. Of these, 62 percent were on warfarin monotherapy, while the remaining 38 percent were treated with warfarin-aspirin combination therapy (56.7 percent males). Combination therapy recipients were also older than those on monotherapy (mean age, 70.2 vs 63.7 years). Mean follow-up duration was 21.2 months. [ASH 2017, Abstract 220]
Patients on combination therapy had a higher mean HAS-BLED** score (2.4 vs. 1.8; p<0.001) and CCI*** (4.8 vs 3.6; p<0.001) compared with those on monotherapy.
Furthermore, there was a higher rate of ischaemic/embolic strokes (0.7/100 patient-years [PY] vs 0.4/100 PY; p=0.02) but a lower incidence of deep venous thrombosis (0.7 vs 1.3/100 PY; p=0.002) and pulmonary embolism (0.1 vs 0.4/100 PY; p=0.002) among those treated with combination vs monotherapy.
Combination therapy was also associated with a higher likelihood of a major (6.1 percent vs 3.2 percent; p<0.001) or non-major (22.9 percent vs 18.7 percent; p=0.004) bleeding event at 1 year, as well as a higher rate of hospitalization for bleeding (8.4 vs 5.7/100 PY; p<0.001), blood transfusions (5.2 vs 4.1/100 PY; p=0.009), and all-cause mortality compared with monotherapy (4.1 vs 3.1/100 PY; p=0.005).
These findings support previous evidence suggesting no benefit and increased bleeding risk associated with warfarin-aspirin combination therapy, which have limited indications (ie, mechanical heart valves, or after percutaneous coronary intervention or acute coronary syndrome). [J Thorac Cardiovasc Surg 2014;148:e1-132; Circulation 2017;135:e1195; Chest 2012;141:e531S-600S; J Am Coll Cardiol 2013;61:e78-140]
Despite the large sample size, patients’ changing medications might not have been properly monitored thus limiting the findings, said Schaefer.
When asked how providers can be encouraged to stop aspirin when not needed, Schaefer highlighted the importance of history taking upon enrolment to be able to immediately flag inappropriate aspirin use, as most patients initiated on warfarin are already taking or consequently given aspirin due to other comorbidities.
Additionally, it is important to increase existing evidence to support guideline recommendations and provide more literature for clinicians who want to discontinue aspirin among patients using it inappropriately, noted Schaefer. “It is not clear what other patient populations should receive combination therapy … Further research is needed to better stratify who should receive aspirin while on warfarin.”