{"id":"fee45c203c2c","type":"article","url":"https://hartvaat.nl/2017/05/01/langetermijnveiligheid-van-zeer-lage-ldl-cholesterolniveaus-improve-it-analyse/","title":"Langetermijnveiligheid van zeer lage LDL-cholesterolniveaus: IMPROVE-IT-analyse","title_en":"Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol : A Prespecified Analysis of the IMPROVE-IT Trial.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["diabetes-en-hart","dyslipidemie","ezetimibe","familiaire-hypercholesterolemie-screening","ldl-cholesterol","lipidenverlaging","niet-statine-therapie","pcsk9-remmers","pelacarsen","statines"],"journal":"JAMA cardiology","doi":"10.1001/jamacardio.2017.0083","source_url":"https://doi.org/10.1001/jamacardio.2017.0083","authors":["Robert P Giugliano","Stephen D Wiviott","Michael A Blazing","Gaetano M De Ferrari","Jeong-Gun Park","Sabina A Murphy","Jennifer A White","Andrew M Tershakovec","Christopher P Cannon","Eugene Braunwald"],"significance":8,"published":"2017-05-01","source_date":"2017-05-01","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"This prespecified IMPROVE-IT analysis showed that achieving very low LDL cholesterol levels (as low as 30 mg/dL) with ezetimibe/simvastatin was safe over 6 years without excess adverse events. The safety data provided reassurance for the growing practice of aggressive LDL lowering.","created":"2026-07-03T10:26:41Z","updated":"2026-07-03T13:26:00Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"JAMA Cardiology gespecificeerde analyse van IMPROVE-IT naar de langetermijnveiligheid van het bereiken van zeer lage LDL-niveaus. Geruststellend voor intensieve LDL-verlaging.","abstract_original":"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."}