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Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

ABSTRACT: The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine.Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (? 2 attacks/week), CAD history, ? 3 transient myocardial ischaemia (TMI) episodes, and/or ? 15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26. There was a comparable, highly significant decrease in TMI with amlodipine and atorvastatin, but no additional benefit for the combination. More than 50% of patients became TMI-free in all three groups and this was accompanied by a comparable, marked reduction in angina and nitroglycerin consumption. High-sensitivity C-reactive protein fell by 40% in patients receiving atorvastatin but there was no change with amlodipine. Adverse events were comparable among groups.Atorvastatin was as potent an anti-ischaemic agent as amlodipine. Future studies of combination therapies will be instructive.National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/.

SUBMITTER: Deanfield JE

PROVIDER: S-EPMC2966969 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

Deanfield John E JE Sellier Phillipe P Thaulow Erik E Bultas Jan J Yunis Carla C Shi Harry H Buch Jan J Beckerman Bruce B

European heart journal 20100521 21

<h4>Aims</h4>The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine.<h4>Methods and results</h4>Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: ...[more]

PMID: 20494902

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Project description:Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs) contributing to this variation, we performed a combined analysis of genome-wide association (GWA) results from three trials of statin efficacy.Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks), Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks), and Treating to New Targets (10 mg/day atorvastatin, 8 weeks). Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8)). This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6)). Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol.Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin, pravastatin, or atorvastatin, we have identified SNPs that may be associated with variation in the magnitude of statin-mediated reduction in total and LDL-cholesterol, including one in the CLMN gene for which statistical evidence for association exceeds conventional levels of genome-wide significance.PRINCE and TNT are not registered. CAP is registered at Clinicaltrials.gov NCT00451828.

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Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

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Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

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