03840nab a2200421 i 4500 publ24064 20241217173112.0 220412s2017 hu o 000 eng d 0028-4793 10.1056/NEJMoa1615664 doi 32750827 mtmt SZTE Publicatio Repozitórium hun eng Sabatine Marc S. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease [elektronikus dokumentum] / Sabatine Marc S. 2017 1713-1722 NEW ENGLAND JOURNAL OF MEDICINE 376 No. 18 Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years.At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%).In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633 .). Klinikai orvostan Giugliano Robert P. aut Keech Anthony C. aut Honarpour Narimon aut Wiviott Stephen D. aut Murphy Sabina A. aut Kuder Julia F. aut et al. aut FOURIER Steering Committee and Investigators aut Tóth Kálmán aut László Zoltán aut Merkely Béla Péter aut Piros Györgyike Ágnes aut Nagy András aut Papp Előd aut Kiss Róbert Gábor aut Karádi István aut et al. aut http://publicatio.bibl.u-szeged.hu/24064/1/Sabatine.pdf Dokumentum-elérés