Net clinical benefit of antithrombotic therapy in patients with heart failure and sinus rhythm: A network meta-analysis from 5 clinical trials

Abstract

Background: Heart failure (HF) is associated with an increased incidence of thromboembolic events. Antithrombotic treatment could reduce the stroke risk, whereas increase the bleeding risk. Whether antithrombotic treatment should be a routine therapy for HF and sinus rhythm (SR) patients remains unanswered.

Methods: We systematically searched Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website for randomized controlled trials (RCTs) studying antithrombotic therapy in HF and SR patients. The primary outcomes of efficacy and safety were defined as stroke and major bleeding, respectively. The network meta-analysis was conducted. The results were expressed as relative risks (RRs) with 95% confidence intervals (95% CIs), and pooled using a random-effects model. The surface under the cumulative ranking curves (SUCRA) was calculated and trade-off analysis of net clinical benefit (NCB) was estimated.

Results: Five studies totally involving 9390 patients were included. A significantly decreased risk of stroke was found for patients with HF and SR, when rivaroxaban was compared with placebo (RR: 0.67, 95%CI: 0.47-0.96) and warfarin was compared with antiplatelets (RR: 0.49, 95%CI: 0.33-0.73). Warfarin (RR: 7.96, 95%CI: 1.06-59.88) and rivaroxaban (RR: 1.65, 95%CI: 1.16-2.33) were associated with a significant increase in the risk of major bleeding when compared with placebo. Considering the ranking of each antithrombotic therapy for primary outcomes, warfarin (SUCRA: 78.2) emerged with the highest cumulative ranking probability for stroke, with rivaroxaban (SUCRA: 73.9) and antiplatelet agents (SUCRA: 19.6) ranked behind. In terms of major bleeding, rivaroxaban (SUCRA: 57.6) was the safer intervention compared with antiplatelet agents (SUCRA: 43.5) or warfarin (SUCRA: 2.9). No difference was observed considering all-cause death, MI and hospitalization of HF among all different antithrombotic regimens. Rivaroxaban was considered as a reasonably effective and the safe antithrombotic agent for HF and SR patients.

Conclusions: Rivaroxaban might the optimal antithrombotic regimen balancing stroke and major bleeding for HF patients with SR. The results might support the attempt to anticoagulation on HF and SR patients. However, further specialized designs of RCTs are necessary to draw a robust conclusion.

Keywords: Heart failure (HF); Net clinical benefit (NCB); Network meta-analysis (NMA); Oral antithrombotic therapy; Sinus rhythm (SR); Trade-off analysis.