Abstract 3022: Clopidogrel Improves Vascular Function and NT-proBNP Levels in Patients With Ischemic Cardiomyopathy
Various in vitro and in vivo observations indicate vasoprotective actions of clopidogrel beyond its antiaggregatory effects. In this prospective, double-blind, randomized study we sought to evaluate whether clopidogrel in comparison to ASS displays such pleiotropic effects in patients with left ventricular dysfunction.
Methods and results: 63 consecutive patients with an ejection fraction below 40% and angiographic evidence of coronary artery disease were randomized to either receive ASS 100mg/d or clopidogrel 75mg/d for 12 weeks. Ultrasono-graphic assessment of brachial flow mediated dilation (FMD) and determination of different inflammatory markers as well as B-natriuretic peptide (NT-proBNP) was performed at baseline and after 3 months. Patients receiving clopidogrel showed a significant improvement in FMD as compared to those receiving ASS (6.65±4.19 to 9.57±6.37, p=0.01 for clopidogrel vs. 7.80±5.05 to 8.23±4.55, p=0.48 for ASS). Moreover, plasma levels of RANTES, a marker of platelet activation, significantly declined after 3 months in the clopidogrel arm (4636.0 [interquartile range: 1941.0 – 6901.0] to 3117.4 [IR: 1347.3–3683.8] pg/ml, p<0.01). Clopidogrel did not significantly affect the levels of inflammatory markers such as hsCRP and MPO, respectively. Interestingly, clopidogrel treatment decreased plasma NT-proBNP levels after 3 months as compared to the ASS arm (311.0 [interquartile range: 170.0 – 830] to 229.5 [IR:120.5– 413.3] ng/ml, p=0.02). However, assessment of left ventricular cardiac function and dimensions with MRI revealed no advantageous effects of Clopidogrel over ASS, which suggests that the improved endothelial function with its potential effects on afterload might be the cause for the decreased NT-proBNP levels.
Conclusion: Our study for the first time displays long term NO preserving and NT-proBNP lowering effects of clopidogrel in a high risk group of patients with heart failure. These data reflect the significance of platelet activation for regulation of vascular NO bioavailability in heart failure. Given the prognostic implications of endothelial function and circulating levels of NT-proBNP in heart failure clopidogrel may evolve as an adjunct treatment strategy in this disease.