Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol : A Prespecified Analysis of the IMPROVE-IT Trial
Giugliano RP, Wiviott SD, Blazing MA, De Ferrari GM, Park JG, Murphy SA, White JA, Tershakovec AM, Cannon CP, Braunwald E
JAMA cardiology · 167 citas
Etiquetas de revisión
Financiación no declaradaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
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 no declarada
Publicación
- Publicado
- 2017-03-14 · JAMA Cardiol · vol. 2 · número 5 · pág. 547
- Editorial
- American Medical Association
- Citado
- 205 citas · más que el 100% de estudios similares · 20.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 31 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Acute Myocardial Infarction Research · Antiplatelet Therapy and Cardiovascular Diseases
- Palabras clave
- very low LDL cholesterol, ezetimibe/simvastatin, simvastatin, long-term safety, cardiovascular events, acute coronary syndrome, drug discontinuation, adverse drug reactions, hemorrhagic stroke, heart failure, cancer, statin therapy, hypercholesterolemia, cardiovascular risk reduction
- MeSH
- humans, neoplasms, muscular diseases, rhabdomyolysis, liver diseases, cardiovascular diseases, myocardial infarction, anticholesteremic agents, treatment outcome, multivariate analysis, proportional hazards models, longitudinal studies, double-blind method, aged, middle aged, patient care planning, female, male, cholesterol, ldl, practice guidelines as topic, stroke, acute coronary syndrome, ezetimibe, simvastatin drug combination
10 autores
- Robert Patrick Giugliano🇺🇸 · autor de correspondenciaBrigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Stephen D. Wiviott🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Michael A. Blazing🇺🇸Duke University
- Gaetano Maria De Ferrari🇮🇹Policlinico San Matteo Fondazione
- Jeong‐Gun Park🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Sabina A. Murphy🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Jennifer A. White🇺🇸Duke University
- Andrew M. Tershakovec🇺🇸Merck & Co., Inc., Rahway, NJ, USA (United States)
- Christopher Paul Cannon🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
- Eugene Braunwald M. D🇺🇸Brigham and Women's Hospital; Thrombolysis in Myocardial Infarction Study Group
Resumen
El texto original del estudio, en el idioma en que se publicó.
Importance
In the Improved Reduction of Outcomes: Vytorin Efficacy International Trial, intensive low-density lipoprotein cholesterol (LDL-C)-reducing therapy with ezetimibe/simvastatin compared with simvastatin alone was associated with a significant reduction in cardiovascular events in 18 144 patients after acute coronary syndrome. The safety of very low LDL-C levels over the long-term is unknown.
Objective
To assess the safety and clinical efficacy of achieving a very low (<30 mg/dL) level of LDL-C at 1 month using data from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial.
Design, setting, and participants
This prespecified analysis compared outcomes in patients stratified by achieved LDL-C level at 1 month in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial and adjusted for baseline characteristics during 6 years' median follow-up. Patients were enrolled from October 26, 2005, to July 8, 2010, and the data analysis was conducted from December 2014 to February 2017.
Main outcomes and measures
Safety end points included adverse events leading to drug discontinuation; adverse muscle, hepatobiliary, and neurocognitive events; and hemorrhagic stroke, heart failure, cancer, and noncardiovascular death. Efficacy events were as specified in the overall trial.
Results
Among the 15 281 patients included in the study, 11 645 (76.2%) were men and the median age was 63 years (interquartile range, 56.6-70.7 years). In these patients without an event in the first month, the achieved LDL-C values at 1 month were less than 30 mg/dL, 30 to 49 mg/dL, 50 to 69 mg/dL, and 70 mg/dL or greater in 6.4%, 31%, 36%, and 26% of patients, respectively. Patients with LDL-C values less than 30 mg/dL (median, 25 mg/dL; interquartile range, 21-27 mg/dL) at 1 month were more likely randomized to ezetimibe/simvastatin (85%), had lower baseline LDL-C values, and were more likely older, male, nonwhite, diabetic, overweight, statin naive, and presenting with a first myocardial infarction. After multivariate adjustment, there was no significant association between the achieved LDL-C level and any of the 9 prespecified safety events. The adjusted risk of the primary efficacy composite of cardiovascular death, major coronary events, or stroke was significantly lower in patients achieving an LDL-C level less than 30 mg/dL at 1 month (adjusted hazard ratio, 0.79; 95% CI, 0.69-0.91; P = .001) compared with 70 mg/dL or greater.
Conclusions and relevance
Patients achieving an LDL-C level less than 30 mg/dL at 1 month had a similar safety profile (and numerically the lowest rate of cardiovascular events) over a 6-year period compared with patients achieving higher LDL-C concentrations. These data provide reassurance regarding the longer-term safety and efficacy of the continuation of intensive lipid-lowering therapy in very higher-risk patients resulting in very low LDL-C levels.
Trial registration
clinicaltrials.gov Identifier: NCT00202878.
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