Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk)
Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda AL, Kanevsky E, Kuder J, Murphy SA, Jukema JW, Lewis BS, Tokgozoglu L, Somaratne R, Sever PS, Pedersen TR, Sabatine MS
Circulation · 571 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
- National Institute for Health Research (NIHR)
- Subvenciones
- National Institute for Health and Care Research (NF-SI-0513-10059)
Según 2 financiadores declarados.
Publicación
- Publicado
- 2017-11-13 · Circulation · vol. 137 · número 4 · págs. 338–350
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 767 citas · más que el 100% de estudios similares · 75.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 43 trabajos
- Acceso
- Acceso abierto (copia en repositorio) · OTHER-OA
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Peripheral Artery Disease Management · Atherosclerosis and Cardiovascular Diseases
- Palabras clave
- evolocumab, PCSK9 inhibitors, peripheral arterial disease, LDL cholesterol lowering, major adverse limb events, acute limb ischemia, major amputation, cardiovascular events, FOURIER trial, statin therapy, atherosclerosis, acute coronary syndrome, acute myocardial infarction, acute stroke, acute myocardial infarction prevention
- MeSH
- humans, antibodies, monoclonal, anticholesteremic agents, serine proteinase inhibitors, treatment outcome, limb salvage, risk factors, down-regulation, time factors, aged, middle aged, female, male, dyslipidemias, cholesterol, ldl, peripheral arterial disease, antibodies, monoclonal, humanized, biomarkers, proprotein convertase 9, pcsk9 inhibitors, amputation, surgical
15 autores
- Marc P. Bonaca🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Patrice Nault🇨🇦McGill University
- Robert Patrick Giugliano🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- ANTHONY C. KEECH🇦🇺The University of Sydney; National Health and Medical Research Council
- Armando Lira Pineda🇺🇸Amgen (United States)
- Estella Kanevsky🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Julia Kuder🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Sabina A. Murphy
- J. Wouter Jukema🇳🇱Leiden University Medical Center
- Basil S. Lewis🇮🇱Technion – Israel Institute of Technology; Carmel Medical Center
- Lâle Tokgözoğlu🇹🇷Hacettepe University
- Ransi M. Somaratne🇺🇸Amgen (United States)
- Peter Sever🇬🇧Imperial College London
- Terje Rolf Pedersen🇳🇴Oslo University Hospital; University of Oslo
- Marc Steven Sabatine🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events.
Methods
FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years. Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of <0.85, or if they had a prior peripheral vascular procedure. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularization. The key secondary end point was a composite of cardiovascular death, myocardial infarction, or stroke. An additional outcome of interest was major adverse limb events defined as acute limb ischemia, major amputation, or urgent peripheral revascularization for ischemia.
Results
Three thousand six hundred forty-two patients (13.2%) had PAD (1505 with no prior myocardial infarction or stroke). Evolocumab significantly reduced the primary end point consistently in patients with PAD (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.0098) and without PAD (HR 0.86; 95% CI, 0.80-0.93; P=0.0003; Pinteraction=0.40). For the key secondary end point, the HRs were 0.73 (0.59-0.91; P=0.0040) for those with PAD and 0.81 (0.73-0.90; PPinteraction=0.41). Because of their higher risk, patients with PAD had larger absolute risk reductions for the primary end point (3.5% with PAD, 1.6% without PAD) and the key secondary end point (3.5% with PAD, 1.4% without PAD). Evolocumab reduced the risk of major adverse limb events in all patients (HR, 0.58; 95% CI, 0.38-0.88; P=0.0093) with consistent effects in those with and without known PAD. There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events (P=0.026 for the beta coefficient) that extended down to <10 mg/dL.
Conclusions
Patients with PAD are at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions. Moreover, lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events.
Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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