Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR, FOURIER Steering Committee and Investigators
The New England journal of medicine · 4,638 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institute for Health and Care Research
- Gobierno
- Medical Research Council
- Gobierno
- National Institute for Health Research (NIHR)
- Subvenciones
- Medical Research Council (MC_EX_MR/M009203/1); Medical Research Council (MC_PC_14089); National Institute for Health and Care Research (NF-SI-0513-10059)
Según 3 financiadores declarados.
Publicación
- Publicado
- 2017-03-17 · N Engl J Med · vol. 376 · número 18 · págs. 1713–1722
- Editorial
- Massachusetts Medical Society
- Citado
- 6,121 citas · más que el 100% de estudios similares · 608.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 28 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Atherosclerosis and Cardiovascular Diseases · Acute Myocardial Infarction Research
- Palabras clave
- evolocumab, PCSK9 inhibition, LDL cholesterol lowering, atherosclerotic cardiovascular disease, cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, statin therapy, LDL cholesterol levels, new-onset diabetes, injection site reactions, primary prevention of cardiovascular disease, LDL-C lowering therapy
- MeSH
- humans, cardiovascular diseases, hypercholesterolemia, antibodies, monoclonal, anticholesteremic agents, hydroxymethylglutaryl-coa reductase inhibitors, drug therapy, combination, incidence, least-squares analysis, follow-up studies, double-blind method, aged, middle aged, female, male, atherosclerosis, cholesterol, ldl, antibodies, monoclonal, humanized, proprotein convertase 9, pcsk9 inhibitors
12 autores
- Marc Steven Sabatine🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Harvard University; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Robert Patrick Giugliano🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Harvard University; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- ANTHONY C. KEECH🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; National Health and Medical Research Council; Imperial College London
- Narimon Honarpour🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Amgen (United States); University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Stephen D. Wiviott🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Harvard University; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Sabina A. Murphy🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Harvard University; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Julia Kuder🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Harvard University; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Huei Wang🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Amgen (United States); University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Thomas Liu🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Amgen (United States); University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Scott M. Wasserman🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; Amgen (United States); University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Peter Sever🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
- Terje Rolf Pedersen🇳🇴🇺🇸🇦🇺🇬🇧Oslo University Hospital; Brigham and Women's Hospital; The University of Sydney; University of Oslo; Thrombolysis in Myocardial Infarction Study Group; Imperial College London
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
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.
Methods
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.
Results
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%).
Conclusions
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 .).
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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