Prospective, randomized, placebo-controlled, double-blind, multicenter study of exercise with enoxaparin pretreatment for stable-effort angina

In this double-blind, placebo-controlled, multicenter trial, we examined the combined effects of repeated exercise and intravenous enoxaparin (low-molecular-weight heparin) on treadmill exercise capacity and angiographic collateral growth and compared them with the effect of repeated exercise with placebo. Fifty-two patients with stable-effort angina were randomly assigned to receive one of two doses of enoxaparin (40 or 60 mg) or placebo. In each patient, 20 treadmill exercise sessions were performed with the pretreatment of enoxaparin or placebo for 2 to 3 weeks. Before and after treatment, coronary cineangiography was repeated to evaluate the changes in coronary and collateral circulation. Improvement of rate-pressure product (RPP) at the onset of angina was taken as an index of enhanced collateral flow reserve. Although the mean differences in the magnitude of increase in RPP were not significantly different between the 3 groups, a heterogeneous response was observed: 1620 beats/min · mm Hg in 40 mg ( p = 0.012). 3060 beats/min · mm Hg in 60 mg ( p = 0.02), and 1090 beats/min · mm Hg in placebo ( p = 0.44). The end-points of the exercise test were changed from chest discomfort to leg fatigue or dyspnea in 10 (28%) of 36 enoxaparin-treated patients but in only 1 (6%) of 16 placebo patients ( p = value not significant (NSS)). Similarly, the extent of coronary and collateral circulation to the completely obstructed coronary artery was increased in 17 (47%) of 36 enoxaparin-treated patients but only in 4 (25%) of 18 placebo patients ( p = NS). In this short-term study in patients with chronic-effort angina, treatment with a combination of exercise and enoxaparin resulted in a statistically significant improvement in treadmill exercise capacity, presumably as a result of the growth of collaterals to the jeopardized myocardium.