Comparative effectiveness of warfarin management strategies: a systematic review and network meta-analysis

Abstract

Background: The management of warfarin therapy presents clinical challenges due to its narrow therapeutic index. We aimed to evaluate the comparative effectiveness of different management strategies in patients using warfarin.

Methods: PubMed, Embase, Cochrane CENTRAL, CINAHL, and EBSCO Open Dissertation were searched from inception to 8 May 2024. Randomized controlled trials that compared the following interventions: patient self-management (PSM), patient self-testing (PST), anticoagulation management services (AMS), and usual care in patients prescribed warfarin for any indication were included. Risk ratios (RR) with 95% confidence interval (CI) were estimated using a random-effects model. Surface under the cumulative ranking curves (SUCRA) were used to rank different interventions. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) online platform. This study is registered with PROSPERO (CRD42023491978).

Findings: Twenty-eight trials involving 8100 participants were included, with follow-up periods of 1-24 months. Mean warfarin dosages were 4.9-7.2 mg/day. Only PSM showed a significant reduction of major TE risk compared with usual care (RR = 0.41; 95% CI: 0.24, 0.71; I² = 0.0%) with moderate certainty of evidence. The 97.6% SUCRA also supported the beneficial effects of PSM over other interventions. The combined direct and indirect evidence showed significantly higher TTR in PSM compared with usual care (MD = 7.39; 95% CI: 2.39, 12.39), with very low certainty. However, direct evidence showed non-significant TTR improvement (MD = 6.49; 95% CI: -3.09, 16.07, I² = 96.1%). No differences across various strategies were observed in all-cause mortality, major bleeding, stroke, transient ischemic attack, and hospitalization.

Interpretation: PSM reduces the risk of major TE events compared with usual care, tends to improve anticoagulation control, and should be considered where appropriate.

Funding: Agency for Healthcare Research and Quality (grant ID 5R18HS027960).

Keywords: Anticoagulation management service; Self-management; Self-monitoring; Self-testing; Warfarin.

Fig. 1

PRISMA flow diagram of selected articles.

Fig. 2

Network geometry of treatment comparisons of warfarin self-care. Abbreviations: AMS = Anticoagulation management service; INR = International normalized ratio; PSM = Patient self-management; PST = Patient self-testing; UC = Usual care. The numbers along the connection lines in each network geometry indicate the number of studies for each direct comparison.