Effects of Long-Term Therapy with the Association of Nisoldipine and a Beta-Blocker on Exercise Tolerance and Coronary Hemodynamics in Patients with Stable Angina: A Comparison with Monotherapy

Abstract

The effects on myocardial metabolism and exercise tolerance of long-term therapy with a β-blocker (propranol) or with the combination of a β-blocker with nisoldipine were studied in 31 patients with chronic stable angina. Ten patients received propranolol and 21 received the combination of propranolol and nisoldipine. Before the study a bicycle ergometry test was performed. Coronary sinus (CS) blood flow and CS and arterial blood samples were obtained at fixed heart rate (atrial pacing) at 10% above control resting sinus rhythm (basal conditions). Measurements were repeated during a pacing stress test at 135 beats/min. A second set of data was collected after 1 month of therapy. Exercise duration increased more with combined therapy than with propranolol alone (+63 ± 14 SEM s vs + 15 ± 15 s; P < 0.05), whereas the maximal exercise heart rate during therapy (118 ± 3 beats/min vs 121 ± 5 beats/min with propranolol) was of the same magnitude. Mean arterial pressure was insignificantly affected by propranolol but decreased significantly with the combined treatment, both in the basal state (94 vs 87 mmHg; (P < 0.05) and during the pacing stress test (97 vs 87 mmHg; P < 0.01). CS flow and myocardial O2 uptake tended to decrease in both groups. Coronary vascular resistance increased slightly in propranolol-treated patients (+9% in basal state and during pacing stress test) and tended to decrease in patients treated with the combination (–5%). These changes in O2 uptake, flow and resistance were not significantly different between groups. In the basal state the lactate extraction fraction did not improve in propranolol-treated patients (26% vs 25%; NS), and myocardial release of alanine increased (from −0.2 ± 1.1 to −2.2 ± 0.6 µmole/min; P < 0.05). In contrast the lactate extraction fraction improved (from 17% ± 3% to 35% ± 3%; P < 0.0001) in patients treated with the combination, and alanine production was reduced by 24% (NS). Changes in myocardial metabolism during the pacing stress test paralleled those observed in the basal state. It is concluded that the combination of nisoldipine with propranolol is superior to monotherapy with the β-blocker not only in terms of clinical results but also in terms of more favourable effects on myocardial metabolism. As changes in O2 uptake or CS flow cannot directly explain the beneficial effect of nisoldipine, these results suggest a direct positive effect of the calcium antagonist on myocardial metabolism.