A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes


© 2018, © The European Society of Cardiology 2018. Background: The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design: Bayesian network meta-analysis was conducted to compare treatment groups. Methods: Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results: In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion: PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.






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Publication Info

Khan, Safi U, Swapna Talluri, Haris Riaz, Hammad Rahman, Fahad Nasir, Irbaz Bin Riaz, Sudhakar Sattur, Haitham Ahmed, et al. (2018). A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes. European Journal of Preventive Cardiology, 25(8). pp. 844–853. 10.1177/2047487318766612 Retrieved from https://hdl.handle.net/10161/17951.

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Richard Andrew Krasuski

Professor of Medicine

Dr. Richard Krasuski is Director of the Adult Congenital Heart Center at Duke University Medical Center, the Director of Hemodynamic Research, and the Medical Director of the CTEPH Program. He is considered a thought leader in the fields of pulmonary hypertension and congenital heart disease. His research focus is in epidemiologic and clinical studies involving patients with pulmonary hypertension and patients with congenital heart disease. He is involved in multiple multicenter studies through the Alliance for Adult Research in Congenital Cardiology (AARCC). He has also helped to develop multiple research databases in these patient populations. He is Co-PI in the upcoming EPIPHANY Study examining the impact of medical and transcatheter interventions on RV-PA coupling in patients with chronic thromboembolic pulmonary hypertension. Over his career he has mentored over 80 students, residents and fellows and has published over 300 peer reviewed publications, book chapters and meeting abstracts. He is also the Chief Editor of Advances in Pulmonary Hypertension and on the editorial boards of several leading medical journals.

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