ANGIOGENIC EFFECTS OF LOW-MOLECULAR-WEIGHT HEPARIN IN PATIENTS WITH STABLE CORONARY-ARTERY DISEASE - A PILOT-STUDY

Objectives. The study was designed to assess the feasibility of conduc ting a trial to investigate whether exercise and low molecular weight heparin therapy with dalteparin sodium (Fragmin) would improve collate ral function to the ischemic myocardium in patients with coronary arte ry disease. Background. The severity of myocardial ischemia in patient s with coronary artery disease is at least partly dependent on the sta tus of the collateral circulation. Therefore, improvement in collatera l function would potentially provide a unique way of alleviating myoca rdial ischemia. Because the combination of ischemia and heparin has pr eviously been demonstrated to enhance collateral growth, we studied th e anti-ischemic effects of combined treatment with dalteparin sodium a nd exercise-induced ischemia in patients with coronary artery disease. Methods. Twenty-three patients with stable coronary artery disease we re randomized to receive either subcutaneous dalteparin sodium or plac ebo for a 4-week period. Patients received either placebo or 10,000 IU of dalteparin sodium by subcutaneous injection once daily for weeks 1 and 2 and 5,000 IU daily for weeks 3 and 4. During the 1st 2 weeks, p atients were exercised to ischemia three times a day. At baseline and 4 weeks after treatment, treadmill exercise testing, exercise radionuc lide ventriculography and 48-h ambulatory ST segment monitoring were p erformed. Results. Eight (80%) of the 10 dalteparin sodium-treated pat ients compared with 4 (31%) of 13 placebo-treated patients (p < 0.02) had an increased rate-pressure product at the onset of 1 mm of ST segm ent depression. The duration of exercise to ischemia increased in all patients treated with low molecular weight heparin and in 62% of place bo-treated patients (p < 0.03). The number and duration of episodes of ST segment depression during ambulatory monitoring decreased by 30% a nd 35%, respectively (p < 0.05), in the dalteparin sodium group but we re unchanged in the placebo group. The decrease in left ventricular ej ection fraction with exercise was lower in 80% of dalteparin sodium-tr eated patients compared with 54% of placebo-treated patients (p = 0.06 ). When all five factors reflecting collateral function were considere d together in a multivariate analysis of variance, there was a signifi cant improvement in low molecular weight heparin-treated patients comp ared with placebo-treated patients (p = 0.014). Conclusions. This stud y provides preliminary evidence suggesting that exercise and low molec ular weight heparin therapy with dalteparin sodium lessen myocardial i schemia and that the improvement is likely to be mediated by enhanced collateral function.