No effect of highly dosed nitric oxide donor molsidomine on the angiographic restenosis rate after percutaneous coronary angioplasty: a randomized, placebo controlled, double-blind trial.

BACKGROUND: Nitric oxide (NO) counteracts several mechanisms involved in the restenotic process after coronary angioplasty. NO mediates an antiproliferative effect on smooth muscle cells, inhibition of leukocyte-vessel wall interactions, and platelet aggregation and adhesion. Because these effects are mainly dose dependent, NO-releasing drugs have to be applied at a high dose to have an effect on restenotic mechanisms.

OBJECTIVES: To study the effect of the NO donor molsidomine at a high dose of 8 mg tid on angiographic restenosis rate in a randomized, placebo controlled, double-blind trial.

PATIENTS AND METHODS: One hundred and sixty-six patients with de novo stenosis were randomly assigned to molsidomine or placebo treatment for six months (83 patients each). The primary end point was the angiographic restenosis rate at six months. The secondary end points were major adverse cardiac events (MACE) including death, myocardial infarction and revascularization. Analyses were performed by intention to treat.

RESULTS: There were no differences in clinical, procedural and angiographic data, including minimum lumen diameter and reference diameter. Provisional stenting was performed in 28% of patients receiving molsidomine and 25% of patients treated with placebo. All other patients were treated with standard balloon angioplasty. Reangiography rate was 89.3% (molsidomine 90 lesions, placebo 97 lesions). Restenosis rate (greater than 50% diameter stenosis) was not significantly different (molsidomine 25.6% and placebo 29.9%). Patients receiving molsidomine improved significantly more in their anginal class than patients receiving placebo (P<0.026). Occurrence of MACE did not significantly differ between both groups (molsidomine 26.8% and placebo 34.9%, P=0.26).

CONCLUSION: Treatment with the NO donor molsidomine at a high dose of 8 mg tid for six months after coronary angioplasty has no effect on the angiographic restenosis rate. Due to the vasodilating effect of NO, the anginal status improves slightly more in patients receiving molsidomine.