EFFECT OF THE DIRECT NITRIC-OXIDE DONORS LINSIDOMINE AND MOLSIDOMINE ON ANGIOGRAPHIC RESTENOSIS AFTER CORONARY BALLOON ANGIOPLASTY - THE ACCORD STUDY

Background Nitric oxide (NO) donors, in addition to their vasodilator effect, decrease platelet aggregation and inhibit vascular smooth musc le cell proliferation. These actions could have beneficial effects on restenosis after coronary balloon angioplasty. Methods and Results In a prospective multicenter, randomized trial, 700 stable coronary patie nts scheduled for angioplasty received direct NO donors (infusion of l insidomine followed by oral molsidomine) or oral diltiazem. Treatment was started before angioplasty and continued until 12 to 24 hours befo re follow-up angiography at 6 months. The primary study end point was minimal lumen diameter, assessed by quantitative coronary angiography, 6 months after balloon angioplasty. Clinical variables were well matc hed in both groups. However, despite intracoronary administration of i sosorbide dinitrate, the reference diameter in the NO donor group was significantly greater than in the diltiazem group on the preangioplast y, postangioplasty, and follow-up angiograms. Pretreatment with an NO donor was associated with a modest improvement in the immediate angiog raphic result compared with pretreatment with diltiazem (minimum lumin al diameter, 1.94 versus 1.81 mm; P=.001); this improvement was mainta ined at the 6-month angiographic follow-up (minimal lumen diameter, 1. 54 versus 1.38 mm; P=.007). The extent of late luminal narrowing did n ot differ significantly between groups (loss index in the NO donor and diltiazam groups, 0.35+/-0.78 and 0.46+/-0.74, respectively; P=.103). Restenosis, defined as a binary variable (greater than or equal to 50 % stenosis), occurred less often in the NO donor group (38.0% versus 4 6.5%; P=.026). Combined major clinical events (death, nonfatal myocard ial infarction, and coronary revascularization) were similar in the tw o groups (32.2% versus 32.4%). Conclusions Treatment with linsidomine and molsidomine was associated with a modest improvement in the long-t erm angiographic result after angioplasty but had no effect on clinica l outcome. The improved angiographic result related predominantly to a better immediate procedural result, because late luminal loss did not differ significantly between groups.