Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty

Background-The treatment of unstable angina targets the specific pathophysi ological thrombotic process at the site of the active culprit lesion. In un stable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus f ormation. Therefore, the relative benefits of nitroglycerin and heparin mig ht differ in unstable angina associated with restenosis compared with class ic unstable angina. Methods and Results-We randomized 200 patients hospitalized for unstable an gina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, hepari n, their combination, or placebo for 63+/-30 hours. Recurrent angina occurr ed in 75% of patients in the placebo and heparin-alone groups, compared wit h 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requir ing angiography occurred in 22.9%, 29.2%, 4.3%, and 4.2% of patients, respe ctively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1.73, P=NS) for heparin versus no heparin. No patient di ed or suffered myocardial infarction. Conclusions-Intravenous nitroglycerin is highly effective in preventing adv erse ischemic events (recurrent or refractory angina) in patients with unst able angina secondary to restenosis, whereas heparin has no effect.