Rugheed Ghadban1, Tariq Enezate1, Jad Omran1, Rajaa Almourani2, Atul Singla3, Sudarshan Balla1. 1. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri, USA. 2. Division of Endocrinology, Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri, USA. 3. Division of Cardiovascular Medicine, Department of Internal Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Abstract
BACKGROUND: Previous studies of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is) were not designed to detect clinical benefit and were underpowered for this outcome. However, recently published trials reported improvement in clinical outcomes. The aim of this meta-analysis to assess the impact of PCSK9Is on clinical outcomes. METHODS: Medline, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were queried from January 2000 through March 2017. Only randomized controlled trials (RCTs) comparing clinical outcomes in patients treated with PCSK9I versus control group were included. Two independent reviewers selected the studies and extracted data in duplicate. Random-effects meta-analysis was used to pool outcomes across studies. Study endpoints included: major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, coronary revascularization, cardiovascular (CV) mortality and all-cause mortality. RESULTS: A total of 62,776 patients (mean age 61 years, 73% were males) were included from six randomized clinical trials. In comparison to control group, PCSK9I use was associated with lower MACE (RR =0.81, 95% CI, 0.70-0.93, P=0.003), MI (RR =0.78, 95% CI, 0.63-0.97, P=0.03), stroke (RR =0.74, 95% CI, 0.64-0.87, P=0.0002) and coronary revascularization (RR =0.79, 95% CI, 0.73-0.86, P<0.00001). There was no statistically significant difference between both groups in terms of all-cause mortality (RR =1.01, 95% CI, 0.86-1.20, P=0.86) or CV mortality (RR =0.98, 95% CI, 0.78-1.22, P=0.83). CONCLUSIONS: PCSK9Is should be strongly considered to improve clinical outcomes in patients at high risk for atherosclerotic CVD.
BACKGROUND: Previous studies of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is) were not designed to detect clinical benefit and were underpowered for this outcome. However, recently published trials reported improvement in clinical outcomes. The aim of this meta-analysis to assess the impact of PCSK9Is on clinical outcomes. METHODS: Medline, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were queried from January 2000 through March 2017. Only randomized controlled trials (RCTs) comparing clinical outcomes in patients treated with PCSK9I versus control group were included. Two independent reviewers selected the studies and extracted data in duplicate. Random-effects meta-analysis was used to pool outcomes across studies. Study endpoints included: major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, coronary revascularization, cardiovascular (CV) mortality and all-cause mortality. RESULTS: A total of 62,776 patients (mean age 61 years, 73% were males) were included from six randomized clinical trials. In comparison to control group, PCSK9I use was associated with lower MACE (RR =0.81, 95% CI, 0.70-0.93, P=0.003), MI (RR =0.78, 95% CI, 0.63-0.97, P=0.03), stroke (RR =0.74, 95% CI, 0.64-0.87, P=0.0002) and coronary revascularization (RR =0.79, 95% CI, 0.73-0.86, P<0.00001). There was no statistically significant difference between both groups in terms of all-cause mortality (RR =1.01, 95% CI, 0.86-1.20, P=0.86) or CV mortality (RR =0.98, 95% CI, 0.78-1.22, P=0.83). CONCLUSIONS: PCSK9Is should be strongly considered to improve clinical outcomes in patients at high risk for atherosclerotic CVD.
Authors: Alessandro Squizzato; Matteo Basilio Suter; Marta Nerone; Robert Patrick Giugliano; Francesco Dentali; Andrea Maria Maresca; Leonardo Campiotti; Anna Maria Grandi; Luigina Guasti Journal: Intern Emerg Med Date: 2017-07-10 Impact factor: 3.397
Authors: Naveed Sattar; David Preiss; Jennifer G Robinson; C Stephen Djedjos; Mary Elliott; Ransi Somaratne; Scott M Wasserman; Frederick J Raal Journal: Lancet Diabetes Endocrinol Date: 2016-02-08 Impact factor: 32.069
Authors: William E Boden; Jeffrey L Probstfield; Todd Anderson; Bernard R Chaitman; Patrice Desvignes-Nickens; Kent Koprowicz; Ruth McBride; Koon Teo; William Weintraub Journal: N Engl J Med Date: 2011-11-15 Impact factor: 91.245
Authors: Paul M Ridker; James Revkin; Pierre Amarenco; Robert Brunell; Madelyn Curto; Fernando Civeira; Marcus Flather; Robert J Glynn; Jean Gregoire; J Wouter Jukema; Yuri Karpov; John J P Kastelein; Wolfgang Koenig; Alberto Lorenzatti; Pravin Manga; Urszula Masiukiewicz; Michael Miller; Arend Mosterd; Jan Murin; Jose C Nicolau; Steven Nissen; Piotr Ponikowski; Raul D Santos; Pamela F Schwartz; Handrean Soran; Harvey White; R Scott Wright; Michal Vrablik; Carla Yunis; Charles L Shear; Jean-Claude Tardif Journal: N Engl J Med Date: 2017-03-17 Impact factor: 91.245
Authors: Michel Farnier; Peter Jones; Randall Severance; Maurizio Averna; Elisabeth Steinhagen-Thiessen; Helen M Colhoun; Yunling Du; Corinne Hanotin; Stephen Donahue Journal: Atherosclerosis Date: 2015-11-14 Impact factor: 5.162
Authors: Amand F Schmidt; Lucy S Pearce; John T Wilkins; John P Overington; Aroon D Hingorani; Juan P Casas Journal: Cochrane Database Syst Rev Date: 2017-04-28
Authors: C Baigent; L Blackwell; J Emberson; L E Holland; C Reith; N Bhala; R Peto; E H Barnes; A Keech; J Simes; R Collins Journal: Lancet Date: 2010-11-08 Impact factor: 79.321