Evaluation of the cost-effectiveness of novel oral anticoagulants compared to oral anticoagulants in patients with atrial fibrillation: A meta-analysis

Atrial fibrillation has emerged as a critical public health issue worldwide due to its increasing prevalence, association with stroke and thromboembolic complications leading to high morbidity and mortality, and the substantial economic burden it imposes on healthcare systems. For many years, warfarin was the standard anticoagulant therapy; however, the need for frequent INR monitoring and numerous drug–food interactions posed significant challenges in practice. The advent of novel oral anticoagulants (NOACs; dabigatran, rivaroxaban, apixaban, edoxaban), characterized by a more predictable pharmacological profile, fixed dosing, and ease of use without routine monitoring, has rapidly transformed anticoagulation management. Nevertheless, their higher drug costs have raised the necessity for comprehensive cost-effectiveness evaluations. In the Turkish context, no meta-analytic synthesis addressing this issue currently exists. The aim of this thesis is to evaluate the cost-effectiveness of NOACs compared to warfarin in managing atrial fibrillation (AF) and to synthesize international literature through meta-analysis, thereby generating generalizable evidence for policymakers based on incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) measures. Conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42023447453), this systematic review and meta-analysis identified 105 eligible studies out of 14,637 records retrieved from PubMed, Scopus, Web of Science, ScienceDirect, EBSCOhost, Cochrane Library, ClinicalTrials, and Wiley databases. Cost, QALY, and ICER data extracted from the studies were standardized to 2023 purchasing power parity (PPP) and consumer price index (CPI) values. The methodological quality of publications was assessed using the ECOBIAS tool, and a random-effects model was applied in cases of heterogeneity. Publication bias was evaluated using funnel plots as well as Egger's and Begg's statistical tests. The findings revealed that NOACs tend to be cost-effective compared to warfarin in high-income countries, as indicated by positive INB values, whereas in low- and middle-income countries results often favored warfarin due to higher drug costs and lower willingness-to-pay (WTP) thresholds. Among the agents, apixaban demonstrated the most robust cost-effectiveness profile, while results for edoxaban varied across countries; findings for dabigatran and rivaroxaban were more context-dependent. The meta-analysis demonstrated that NOACs are generally more likely to be cost-effective than warfarin in high-income countries, as reflected by positive INB values. In contrast, in low- and middle-income countries, outcomes more often favored warfarin, primarily due to higher drug costs and lower willingness-to-pay (WTP) thresholds. Among individual agents, apixaban exhibited the most consistent and favorable cost-effectiveness profile, while results for edoxaban varied considerably across countries. Findings for dabigatran and rivaroxaban were more context-specific, indicating their cost-effectiveness is highly dependent on the healthcare setting.