Samer Al Said1, Samer Alabed2, Klaus Kaier3, Audrey R Tan4, Christoph Bode1, Joerg J Meerpohl5, Daniel Duerschmied1. 1. University of Freiburg, Department of Cardiology and Angiology I, Heart Center, Freiburg, Germany. 2. University of Sheffield, Academic Unit of Radiology, Sheffield, UK. 3. Faculty of Medicine and Medical Center, University of Freiburg, Institute for Medical Biometry and Statistics, Freiburg, Germany. 4. University College London, Institute of Health Informatics Research, 222 Euston Road, London, UK, NW1 2DA. 5. Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Institute for Evidence in Medicine, Breisacher Str. 153, Freiburg, Germany, D-79110.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: We searched for randomised controlled trials (RCT) that compared NOACs and vitamin K antagonists for people with an indication for anticoagulation who underwent PCI. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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). 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. 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. The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. AUTHORS' CONCLUSIONS: 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. 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. 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.
BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: We searched for randomised controlled trials (RCT) that compared NOACs and vitamin K antagonists for people with an indication for anticoagulation who underwent PCI. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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). 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. 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. The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. AUTHORS' CONCLUSIONS: 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. 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. 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.
Authors: Jeremy S Paikin; Douglas S Wright; Mark A Crowther; Shamir R Mehta; John W Eikelboom Journal: Circulation Date: 2010-05-11 Impact factor: 29.690
Authors: Núria Casamira; Tamara García-Camarero; J Bruno Montoro-Ronsano; Gabriela Veiga; Bruno García Del Blanco; José María De La Torre; Blanca Gordon; David García-Dorado; Antonia Sambola Journal: Am J Med Sci Date: 2019-03-28 Impact factor: 2.378
Authors: Romina Brignardello-Petersen; M Hassan Murad; Stephen D Walter; Shelley McLeod; Alonso Carrasco-Labra; Bram Rochwerg; Holger J Schünemann; George Tomlinson; Gordon H Guyatt Journal: J Clin Epidemiol Date: 2018-09-22 Impact factor: 6.437
Authors: Stephan Windecker; Philippe Kolh; Fernando Alfonso; Jean-Philippe Collet; Jochen Cremer; Volkmar Falk; Gerasimos Filippatos; Christian Hamm; Stuart J Head; Peter Jüni; A Pieter Kappetein; Adnan Kastrati; Juhani Knuuti; Ulf Landmesser; Günther Laufer; Franz-Josef Neumann; Dimitrios J Richter; Patrick Schauerte; Miguel Sousa Uva; Giulio G Stefanini; David Paul Taggart; Lucia Torracca; Marco Valgimigli; William Wijns; Adam Witkowski Journal: Eur Heart J Date: 2014-08-29 Impact factor: 29.983
Authors: Renato D Lopes; John H Alexander; Sana M Al-Khatib; Jack Ansell; Raphael Diaz; J Donald Easton; Bernard J Gersh; Christopher B Granger; Michael Hanna; John Horowitz; Elaine M Hylek; John J V McMurray; Freek W A Verheugt; Lars Wallentin Journal: Am Heart J Date: 2010-03 Impact factor: 4.749
Authors: Clive Kearon; Elie A Akl; Joseph Ornelas; Allen Blaivas; David Jimenez; Henri Bounameaux; Menno Huisman; Christopher S King; Timothy A Morris; Namita Sood; Scott M Stevens; Janine R E Vintch; Philip Wells; Scott C Woller; Lisa Moores Journal: Chest Date: 2016-01-07 Impact factor: 9.410
Authors: Caroline Sindet-Pedersen; Laila Staerk; Morten Lamberts; Thomas Alexander Gerds; Jeffrey S Berger; Anders Nissen Bonde; Jannik Langtved Pallisgaard; Morten Lock Hansen; Christian Torp-Pedersen; Gunnar H Gislason; Jonas Bjerring Olesen Journal: Heart Date: 2017-11-01 Impact factor: 5.994
Authors: Jurriën M ten Berg; Wim B M Gerritsen; Fred J L M Haas; Johannes C Kelder; Freek W A Verheugt; H W Thijs Plokker Journal: Thromb Haemost Date: 2002-12 Impact factor: 5.249
Authors: Katherine C Hocking; Catriona R Wright; Utku Alhun; Frances Hughes; Vartan J Balian; Mohammed A K Kabuli; George Tse; Maria McGonnell; Annu Chopra; Nikhil Kotnis; Daniel Connelly; Samer Alabed Journal: Br J Radiol Date: 2022-01-05 Impact factor: 3.039