Relative efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation by network meta-analysis

Abstract

BackgroundMuch direct evidence has proved that the novel oral anticoagulants (NOACs) are noninferior or superior to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, and lead to a relevant decrease in bleeding profiles. However, no study has compared NOACs with each other head-to-head. The current study is a network meta-analysis aiming to assess the efficacy and safety of NOACs.MethodsCochrane library, Pubmed NCBI, EMBASE and MEDLINE were systematically searched for randomized controlled trials that assessed the efficacy and safety profiles of NOACs compared with warfarin. The primary outcome was the rate of stroke or systemic embolism, and the secondary outcome was the rate of bleeding events. Network meta-analysis was performed using Markov chain Monte Carlo methods.ResultsA total of four phase III randomized controlled trials (n = 71683) met the inclusion criteria. All NOACs except low dose of edoxaban showed noninferior efficacies to warfarin in stroke prevention. In the field of hemorrhage, apixaban was safer than edoxaban 60 mg in any bleeding events and had fewer major bleeding events compared with dabigatran 150 mg and rivaroxaban.ConclusionNOACs are promising candidates for stroke prevention in patients with nonvalvular atrial fibrillation due to a favorable risk–benefit profile. All NOACs other than edoxaban 30 mg had parallel efficacies with respect to stroke prevention. Apixaban had an advantage over the other NOACs in safety.

Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis

“…In other NMAs assessing the efficacy and safety of NOACs in the prevention of thromboembolic events in NVAF patients apixaban was found to be associated with fewer bleeding events compared with edoxaban, dabigatran and rivaroxaban [Fu et al 2014;Mantha and Ansell, 2012;Lip et al 2012]. In a previously published indirect comparison analysis of NOACs on secondary IS prevention in patients with NVAF, dabigatran 110 mg was associated with a lower risk for hemorrhagic stroke (HR 0.15;) and intracranial bleeding (HR 0.27; 95% CI 0.10-0.73) compared with rivaroxaban.…”

Estimating the cost-effectiveness of treatment for prevention of thromboembolic events in at-risk adults with non-valvular atrial fibrillation

“…In pivotal RCTs, DOACs have demonstrated net clinical benefit compared with warfarin, mainly driven by a significant reduction of intracranial bleedings [6][7][8][9]. However, relevant differences in the incidence of major and gastrointestinal bleeding have been observed among DOACs, and apixaban seems to have the best safety profile, with a lower incidence of major bleeding [10][11][12] including gastrointestinal bleeding [13,14]. The economic value of apixaban has been demonstrated in an independent cost-effectiveness analysis conducted in UK and based on the data from a network meta-analysis of 23 RCTs [12], which showed that apixaban has a slightly higher expected quality-adjusted life expectancy (QALYs: 5.49 vs. 5.45 of rivaroxaban, 5.42 of dabigatran 150 mg, and 5.41 of edoxaban 60 mg) and the highest probability of being the most cost-effective first-line therapy for AF (close to 60% for willingness to pay thresholds of £ 20,000-30,000).…”

“…The results show that apixaban has a better safety profile in comparison to the other DOACs. Indeed it was associated with fewer bleeding events of any type (OR = 0.81; CI95%: 0.89-0.74) than edoxaban 60 mg QD and less major and GI bleeds than dabigatran 150 mg (major: OR = 0.75; CI95%: 0.61-0.90; GI: OR = 0.59; CI95%: 0.41-0.82) and rivaroxaban (major: OR = 0.67; CI95%: 0.82-0.55; GI: OR = 0.58; CI95%: 0.86-0.43) [11]. Finally, an indirect comparison analysis based on the phase III clinical trials found that there were no significant efficacy differences between edoxaban 60 mg QD and apixaban 5 mg BID, but apixaban was associated with lower clinically relevant non-major bleeding (HR = 0.79; CI95%: 0.70-0.90) and gastrointestinal bleeding (HR = 0.72; CI95%: 0.55-0.96) [14].…”

“…Edoxaban was included in a network meta-analysis of the four phase III RCTs with the aim to assess the relative efficacy and safety of DOACs [11]. The results show that apixaban has a better safety profile in comparison to the other DOACs.…”

“…The DOACs currently indicated are factor Xa inhibitors apixaban, edoxaban, and rivaroxaban; and the direct thrombin inhibitor dabigatran; they have demonstrated a more predictable effect and a more favorable risk-benefit ratio, without the need for INR monitoring, compared to standard therapy. In phase III trials (Table I), and in several indirect comparisons, both the individual DOACs and the entire class were considered non-inferior, or superior, to warfarin in the reduction of stroke, systemic embolism (SE), intracranial bleeding, and mortality [6][7][8][9][10][11][12][13][14] and are recommended in the first-line treatment of patient with AF in preference to VKAs [1].…”