Non-vitamin K antagonist oral anticoagulants (NOACs) post-percutaneous coronary intervention: a network meta-analysis

Abstract

<div class="section"> <a class="named-anchor" id="CD013252-abs1-0001"> <!-- named anchor --> </a> <h5 class="title" id="d446260e206">Background</h5> <p id="d446260e208">Clinicians must balance the risks of bleeding and thrombosis after percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. The potential of non‐vitamin K antagonists (NOACs) to prevent bleeding complications is promising, but evidence remains limited. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0002"> <!-- named anchor --> </a> <h5 class="title" id="d446260e211">Objectives</h5> <p id="d446260e213">To review the evidence from randomised controlled trials assessing the efficacy and safety of non‐vitamin K antagonist oral anticoagulants (NOACs) compared to vitamin K antagonists post‐percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0003"> <!-- named anchor --> </a> <h5 class="title" id="d446260e216">Search methods</h5> <p id="d446260e218">We identified studies by searching CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index – Science and two clinical trials registers in February 2019. We checked bibliographies of identified studies and applied no language restrictions. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0004"> <!-- named anchor --> </a> <h5 class="title" id="d446260e221">Selection criteria</h5> <p id="d446260e223">We searched for randomised controlled trials (RCT) that compared NOACs and vitamin K antagonists for people with an indication for anticoagulation who underwent PCI. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0005"> <!-- named anchor --> </a> <h5 class="title" id="d446260e226">Data collection and analysis</h5> <p id="d446260e228">Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random‐effects, pairwise analyses using Review Manager 5 and network meta‐analyses (NMA) using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons, and allow ranking of treatments on a continuous 0 to 1 scale. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0006"> <!-- named anchor --> </a> <h5 class="title" id="d446260e231">Main results</h5> <p id="d446260e233">We identified nine RCTs that met the inclusion criteria, but four were ongoing trials, and were not included in this analysis. We included five RCTs, with 8373 participants, in the NMA (two RCTs compared apixaban to a vitamin K antagonist, two RCTs compared rivaroxaban to a vitamin K antagonist, and one RCT compared dabigatran to a vitamin K antagonist). </p> <p id="d446260e235">Very low‐ to moderate‐certainty evidence suggests little or no difference between NOACs and vitamin K antagonists in death from cardiovascular causes (not reported in the dabigatran trial), myocardial infarction, stroke, death from any cause, and stent thrombosis. Apixaban (RR 0.85, 95% CI 0.77 to 0.95), high dose rivaroxaban (RR 0.86, 95% CI 0.74 to 1.00), and low dose rivaroxaban (RR 0.80, 95% CI 0.68 to 0.92) probably reduce the risk of recurrent hospitalisation compared with vitamin K antagonists. No studies looked at health‐related quality of life. </p> <p id="d446260e237">Very low‐ to moderate‐certainty evidence suggests that NOACs may be safer than vitamin K antagonists in terms of bleeding. Both high dose dabigatran (RR 0.53, 95% CI 0.29 to 0.97), and low dose dabigatran (RR 0.38, 95% CI 0.21 to 0.70) may reduce major bleeding more than vitamin K antagonists. High dose dabigatran (RR 0.83, 95% CI 0.72 to 0.96), low dose dabigatran (RR 0.66, 95% CI 0.58 to 0.75), apixaban (RR 0,67 , 95% Cl 0.51 to 0.88), high dose rivaroxaban (RR 0.66, 95% CI 0.52 to 0.83), and low dose rivaroxaban (RR 0.71, 95% CI 0.57 to 0.88) probably reduce non‐major bleeding more than vitamin K antagonists. </p> <p id="d446260e239">The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. </p> </div><div class="section"> <a class="named-anchor" id="CD013252-abs1-0007"> <!-- named anchor --> </a> <h5 class="title" id="d446260e242">Authors' conclusions</h5> <p id="d446260e244">Very low‐ to moderate‐certainty evidence suggests no meaningful difference in efficacy outcomes between non‐vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists following percutaneous coronary interventions (PCI) in people with non‐valvular atrial fibrillation. NOACs probably reduce the risk of recurrent hospitalisation for adverse events compared with vitamin K antagonists. </p> <p id="d446260e246">Low‐ to moderate‐certainty evidence suggests that dabigatran may reduce the rates of major and non‐major bleeding, and apixaban and rivaroxaban probably reduce the rates of non‐major bleeding compared with vitamin K antagonists. </p> <p id="d446260e248">Our network meta‐analysis did not show superiority of one NOAC over another for any of the outcomes. Head to head trials, directly comparing NOACs against each other, are required to provide more certain evidence. </p> </div><p id="d446260e253"> <b>Non‐vitamin K antagonist oral anticoagulants (NOACs) after a heart vessel stent placement</b> </p><p id="d446260e258"> <b>Background</b> </p><p id="d446260e263">Choosing the optimal treatment for people on long term blood thinners (due to atrial fibrillation), who require a heart vessel stent placement (after a heart attack or angina) remains a challenge in clinical practice. They need to take blood thinners to prevent a stroke, and antiplatelet drugs to prevent blood clots in the stents. However, this combination increases the risk of potentially life‐threatening bleeding, and thus, the optimal treatment remains uncertain. The aim of this review was to investigate whether next‐generation blood thinners (NOACs) are safer and more effective than older blood‐thinning medications (such as warfarin) in this group of individuals. </p><p id="d446260e265"> <b>Study characteristics</b> </p><p id="d446260e270">We identified nine studies that compared NOACs with warfarin, four of which were ongoing studies. We included five trials involving 8373 participants in this review. Evidence is current to February 2019. </p><p id="d446260e272"> <b>Key results</b> </p><p id="d446260e277">There may be little or no difference in effect between NOACs and warfarin in people with atrial fibrillation, who underwent heart vessel stenting. However, NOACs probably reduce the need for hospitalisation compared to warfarin. </p><p id="d446260e279">NOACs may be safer than warfarin. One of NOACs drugs (dabigatran) may reduce the rate of both major and non‐major bleeding. Other NOAC drugs (apixaban and rivaroxaban) probably reduce the rate of non‐major bleeding. There was no significant difference between NOACs agents in any primary or secondary outcomes. </p><p id="d446260e281"> <b>Quality of evidence:</b> </p><p id="d446260e286">The evidence ranged from Very low‐ to moderate‐certainty, indicating the need for more research on this issue. </p>