Comparison of efficacy of low- (80 mg/day) and high- (160-320 mg/day) dose valsartan in the prevention of in-stent restenosis after implantation of bare-metal stents in type B2/C coronary artery lesions.
OBJECTIVE
Results from the VALVACE (VALsartan Versus ACE inhibition after bare metal stent implantation) trial suggest that prevention of in-stent restenosis after implantation of bare-metal stents in type B2/C coronary artery lesions is possible after administration of valsartan 80 mg/day. However, the restenosis rate in patients with stable angina was relatively high (27%) with this dosage and no different from patients taking ACE inhibitors. Therefore, a 1 : 1 matched comparison on a case-control basis was initiated in a prospective controlled registry using a higher dose of valsartan, 160-320 mg/day.


METHODS
A total of 450 patients (241 men, mean age 62.7 +/- 9.1 years) with matched demographic and angiographic characteristics to patients in the VALVACE trial were treated with high-dose oral valsartan 160-320 mg/day over 6 months until control angiography. Angiographic restenosis rate, target lesion revascularization (TLR) and target vessel revascularization (TVR) rates, major adverse cardiac event (MACE) rate (death, myocardial infarction, and stent thrombosis) and mean late lumen loss were analysed after 6 months. Results were compared with the results of the VALVACE trial. Analysis of the combined results of the current study together with the VALVACE trial data enabled calculation of the gender- and dose-dependent effects of valsartan.


RESULTS
In the high-dose valsartan group, the angiographic restenosis rate in 368 patients with control angiography was 7.3% compared with 19.5% in the low-dose group (VALVACE) [p < 0.0001]. Mean late lumen loss was 0.37 +/- 0.3 mm in the high-dose group compared with 0.53 +/- 0.31 mm in the VALVACE trial (p < 0.01). TLR and TVR rates were 4.3% in the high-dose group compared with 9% in the VALVACE trial (p < 0.01). The MACE rate was 0% in the high-dose group compared with 1.5% in the VALVACE trial (p < 0.01). Summarizing the data for valsartan, the in-stent restenosis rates in men were 22.7%, 13.3%, 6.7%, and 5.4% in patients receiving 80, 160, 240, and 320 mg/day, respectively. In women, the in-stent restenosis rates were 13.3% and 6.3% in patients receiving 80 and 160 mg/day, respectively; no restenosis occurred in patients receiving higher doses.


CONCLUSIONS
Administration of high-dose oral valsartan 160-320 mg/day after implantation of bare-metal stent in type B2/C coronary artery lesions reduces angiographic in-stent restenosis, TLR, TVR, late lumen loss, and MACE rates more effectively than low-dose valsartan 80 mg/day.
Peters
Stefan
S
Klinikum Quedlinburg, Academic Teaching Hospital of the University Hospital of Magdeburg, Quedlinburg, Germany. s.peters@klinikum-quedlinburg.de
D000284:Administration, Oral; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000628:therapy; D023903:Coronary Restenosis / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D015607:Stents; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine