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Impact of atorvastatin treatment in first-degree relatives of patients with premature coronary artery disease with endothelial dysfunction: a double-blind, randomized, placebo-controlled crossover trial.

ABSTRACT: BACKGROUND:A family history of premature coronary artery disease (CAD) is a well-known risk factor for cardiovascular events. HYPOTHESIS:Atorvastatin may improve endothelial dysfunction (ED) in the first-degree relatives (FDRs) of patients with premature CAD with ED. METHODS:Thirty-five FDRs (median age, 52 years [interquartile range (IQR), 46-57 years], 21 male) of patients with premature CAD with ED were recruited in a prospective trial with a crossover double-blind design: 6 weeks of treatment with atorvastatin 40 mg/day followed by placebo, or vice versa. After each treatment, the digital pulse wave amplitude was determined by EndoPAT to obtain the reactive hyperemia index (RHI), a measure for endothelial function. The primary outcome was the difference of RHI between atorvastatin and placebo treatment. RESULTS:Low-density lipoprotein cholesterol was lower after atorvastatin compared with placebo treatment (124 [102-145] mg/dL vs 67 [50-73] mg/dL, P < 0.001). However, RHI was not different after atorvastatin compared with placebo treatment (1.9 [1.5-2.4] vs 1.9 [1.6-2.2], P = 0.902). Also, the augmentation index was similar after each treatment. These results were observed both in subjects who had indications for statin treatment (31%) and those who did not (69%) according to National Cholesterol Education Program Adult Treatment Panel III guidelines. CONCLUSIONS:Despite improvement in the lipid profile, atorvastatin failed to improve ED in the FDRs of patients with premature CAD with ED. Although we identified those with ED in FDRs of patients with premature CAD as a high-risk group for future cardiovascular events, atorvastatin treatment may not be a beneficial primary prevention strategy for this population.

SUBMITTER: Hong SJ

PROVIDER: S-EPMC6649483 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Impact of atorvastatin treatment in first-degree relatives of patients with premature coronary artery disease with endothelial dysfunction: a double-blind, randomized, placebo-controlled crossover trial.

Hong Sung-Jin SJ Chang Hyuk-Jae HJ Park Sungha S Kang Dae Ryong DR Shin Sanghoon S Shin Sanghoon S Cho In-Jeong IJ Shim Chi Young CY Hong Geu-Ru GR Ha Jong-Won JW Chung Namsik N

Clinical cardiology 20130610 8

<h4>Background</h4>A family history of premature coronary artery disease (CAD) is a well-known risk factor for cardiovascular events.<h4>Hypothesis</h4>Atorvastatin may improve endothelial dysfunction (ED) in the first-degree relatives (FDRs) of patients with premature CAD with ED.<h4>Methods</h4>Thirty-five FDRs (median age, 52 years [interquartile range (IQR), 46-57 years], 21 male) of patients with premature CAD with ED were recruited in a prospective trial with a crossover double-blind desig ...[more]

PMID: 23754711

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Project description:BackgroundGlucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus.MethodsThe LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating?>?0.1 mV of planar or downsloping ST-segment depression (STD). Those randomised to active agent started with a 1-week run-in phase of 0.6 mg liraglutide daily, an established injectable GLP-1R agonist, followed by 1 week of 1.2 mg liraglutide, after which patients performed a week 2 ETT. Patients then self-administered 1.8 mg liraglutide for a week before completing a week 3 ETT. The placebo arm received visually and temporally matched daily saline injections. Participants then crossed over to a 3-week course of saline injections interspersed with a week 5 ETT and week 6 ETT and vice versa. Co-primary endpoints were rate pressure product (RPP) at 0.1 mV STD and magnitude of STD at peak exercise.ResultsTwenty-two patients (21 without diabetes) were randomised. There was no significant difference between saline versus liraglutide in the co-primary endpoints of RPP achieved at 0.1 mV STD (saline vs. liraglutide 1.2 mg p?=?0.097; saline vs. liraglutide 1.8 mg p?=?0.48) or the degree of STD at peak exercise (saline vs. liraglutide 1.2 mg p?=?0.68; saline vs. liraglutide 1.8 mg p?=?0.57). Liraglutide did not cause symptomatic hypoglycaemia, renal dysfunction, acute pancreatitis or provoke early withdrawal from the trial. Liraglutide significantly reduced weight (baseline 88.75?±?16.5 kg vs. after liraglutide 87.78?±?16.9 kg; p?=?0.0008) and improved the lipid profile (mean total cholesterol: at baseline 3.97?±?0.88 vs. after liraglutide 3.56?±?0.71 mmol/L; p?<?0.0001).ConclusionLiraglutide did not enhance exercise tolerance or haemodynamics compared with saline placebo during serial treadmill testing in patients with established obstructive CAD. It did, however, significantly reduce weight and improve the lipid profile. Trial Registration ClinicalTrials.gov Identifier NCT02315001. Retrospectively registered on 11th December 2014.

Dataset Information

Impact of atorvastatin treatment in first-degree relatives of patients with premature coronary artery disease with endothelial dysfunction: a double-blind, randomized, placebo-controlled crossover trial.

Publications

Impact of atorvastatin treatment in first-degree relatives of patients with premature coronary artery disease with endothelial dysfunction: a double-blind, randomized, placebo-controlled crossover trial.

Similar Datasets

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