Influence of baseline lipids on effectiveness of pravastatin in the CARE trial

Pfeffer, Marc A.; Sacks, Frank M.; Moyé, Lemuel A.; East, Cara; Goldman, Steven; Nash, David T.; Rouleau, Jacques R.; Rouleau, Jean L.; Sussex, Bruce; Théroux, Pierre; Belt, Ron J. Vanden; Braunwald, Eugene

doi:10.1016/s0735-1097(98)00522-1

Cited by 75 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CARE trial (22) provided evidence of cardiovascular benefits despite cholesterol levels in the normal range before statin treatment. Furthermore, multiple experimental studies have demonstrated reductions in myocardial infarct size in the absence of cholesterol lowering (16,26).…”

Section: Discussionmentioning

confidence: 99%

“…The cholesterol-lowering effects of statins and their ability to reduce morbidity and mortality in cardiovascular disease have been proven in multiple clinical trials (23a, 24). Although reductions in serum lipids and plaque stabilization may account for part of the clinical benefit of statins (18,19), additional clinical evidence suggests mechanisms independent of diminishing hypercholesterolemia (22). A growing body of evidence implicates improvements in endothelial function and endothelium-derived nitric oxide (NO) as potential mediators (6,17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure

Greer

Kakkar²,

Elrod³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

-methylglutaryl coenzyme A reductase inhibitors increase endothelial nitric oxide synthase (eNOS) activity by multiple mechanisms. We previously reported that genetic overexpression of eNOS improves survival and cardiac function in congestive heart failure (CHF). In the present study, we tested the hypothesis that low-dose treatment with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor exerts beneficial effects on survival and/or cardiac function in a murine model of CHF. Mice were subjected to permanent ligation of the left coronary artery and randomized to receive either saline vehicle or simvastatin (0.25 mg/kg) 2 h after myocardial infarction and daily (0.25 mg/kg) for 7 days, followed by 21 days of administration every other day for a total duration of 28 days. Myocardial infarct size was not reduced by simvastatin therapy (P ϭ not significant between groups). Simvastatin treatment did significantly (P Ͻ 0.05) improve survival (45%) compared with vehicle treatment (25%). In addition, simvastatin treatment significantly improved (P Ͻ 0.01) left ventricular function and significantly (P Ͻ 0.01) abrogated cardiac hypertrophy and pulmonary edema compared with vehicle treatment. The protective effects of simvastatin were abrogated by delayed initiation of treatment or genetic ablation of eNOS. In conclusion, low-dose simvastatin therapy significantly improves survival and cardiac function and reduces both cardiac hypertrophy and pulmonary edema via an eNOS-dependent mechanism in a murine model of CHF.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure

Greer

Kakkar²,

Elrod³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…In the Program On the Surgical Control of the Hyperlipidaemias (POSCH), 15 Scandinavian Simvastatin Survival Study (4S), 16 Cholesterol And Recurrent Events (CARE) 17 and West of Scotland Coronary Prevention Study studies (WOSCOPS), 18 total plasma cholesterol and triglycerides values were positively correlated with cardiovascular risk.…”

Section: Discussionmentioning

confidence: 99%

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

et al. 2002

View full text Add to dashboard Cite

Interindividual variation in the concentration of plasma lipids which are associated with coronary artery disease (CAD) risk is determined by a combination of genetic and environmental factors. This study investigates the effects of apoE genotype and plasma concentration on cholesterol and triglycerides (TG) levels in subjects from five countries: Finland, France, Northern Ireland, Portugal, and Spain. Age and sex significantly influenced serum cholesterol, TG and apoE concentrations. The age effect differs in males and females. The allele frequencies of the apoE gene, one of the most widely studied CAD susceptibility genes, were determined: the e2 allele frequency and the apoE concentration showed a north -south increasing gradient while the e4 allele frequency showed the reverse. ApoE plays an important role in lipid metabolism. Total cholesterol and TG concentrations were significantly dependent on apoE genotype in both sexes. These differences in lipids between genotypes were more pronounced when plasma apoE concentrations were taken into account.

show abstract

“…[18][19][20] Furthermore, in the CARE and LIPID trials, the benefits of pravastatin were diminished in patients with baseline LDL-C values less than 130 mg/dL. 19,21) In contrast, LIPS showed that the benefit of fluvastatin is equal regardless of the baseline cholesterol values, indicating that fluvastatin has beneficial effects other than its lipid-lowering effect in cardiac events. Recent reports have demonstrated that in addition to their lipid-lowering effects, statins have many pleiotropic effects, such as inhibiting oxidative stress, improving endothelial function, decreasing vascular inflammation, and enhancing plaque stability.…”

Section: Discussionmentioning

confidence: 99%

Effects of Statins on Circulating Oxidized Low-density Lipoprotein in Patients With Hypercholesterolemia

et al. 2004

View full text Add to dashboard Cite

SUMMARYRecently, it has been reported that circulating oxidized low-density lipoprotein (Ox-LDL) might be a pivotal indicator for coronary artery disease and the severity of acute coronary syndromes. The purpose of this study was to investigate the effects of statins on Ox-LDL in patients with hypercholesterolemia.Sixteen patients with hypercholesterolemia were randomly assigned to 2 groups, one received 10 mg of pravastatin (n = 8) and the other received 20 mg of fluvastatin (n = 8).The plasma level of Ox-LDL was measured using a newly developed sandwich enzymelinked immunosorbent assay (ELISA) method.There were no differences between the two groups in Ox-LDL, total cholesterol (TC), or LDL cholesterol (LDL-C) at the baseline. The reduction in Ox-LDL in the fluvastatin group was significantly higher than that in the pravastatin group (47.5% versus 25.2%, P = 0.033). The reductions in TC and LDL-C did not differ between the two groups. Conclusion: The present study has shown for the first time that the level of circulating Ox-LDL was significantly decreased by treatment with statins. In addition, the lowering effect of statins on the circulating Ox-LDL was independent of their lipid-lowering effect. Fluvastatin was more effective than pravastatin with regard to decreasing the circulating Ox-LDL. (Jpn Heart J 2004; 45: 969-975)

show abstract

Influence of baseline lipids on effectiveness of pravastatin in the CARE trial

Abstract: Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.

Cited by 75 publications

References 23 publications

Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure

Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

Effects of Statins on Circulating Oxidized Low-density Lipoprotein in Patients With Hypercholesterolemia

Contact Info

Product

Resources

About