The efficacy of combining gallopamil and iso-sorbide-5-mononitrate (IS-5-MN) was evaluated in 15 patients with “mixed” angina and documented coronary artery disease who participated in a 4-week, double-blind, double-dummy, crossover, placebo-controlled trial. After the first week of the placebo phase (single-blinded), all patients received in three different weeks IS-5-MN 20 mg three times daily, gallopamil 50 mg three times daily, and the same dosages of IS-5-MN and gallopamil three times daily. Exercise tolerance, and peak values of heart rate, systolic blood pressure, double product (DP/100), and ST-segment were evaluated with a treadmill test at the end of each phase. The improvement in exercise tolerance obtained by the combination of the two drugs was significantly greater (p < 0.01) than that achieved by IS-5-MN but not that by gallopamil monotherapy (NS). This effect was accompanied by significant (p < 0.05) reduction (-61%) in ST-segment and significant (p < 0.05) increment ( + 8%) in peak heart rate only after administration of the combination of the two drugs. The number of ST-depression (ST-) > 1 mm or ST-elevation (ST + ) episodes on 24-h Holter monitoring lasting ≥ 1 min were also noted in all patients at the end of each phase of the trial. Sixty-five (14 ST-, 51 ST + ) transient myocardial ischemic episodes were recorded on Holter monitoring during the placebo phase; 4 (ST-) during IS-5-MN phase (94% decrease p < 0.001); 9 (7 ST-, 2 ST+ ) during the gallopamil phase (84% decrease, p < 0.01); and 8 (5 ST- , 3 ST + ) during the combination phase (87% decrease p < 0.01). The effects obtained during the IS-5-MN phase were significantly greater (p < 0.05) than those observed during the gallopamil phase but not than those obtained during the combination phase (NS). Of the total transient myocardial ischemic episodes, 98% were painless and 88% were not preceded by an increase in heart rate. When compared with placebo, both IS-5-MN and gallopamil, alone and combined, improved exercise tolerance by 29% (p < 0.01), 33% (p < 0.01), and 38% (p < 0.001), respectively. Combining IS-5-MN and gallopamil was thus highly effective toward both painful demand and spontaneous silent ischemic events that occurred in patients with “mixed” angina and significantly better than either drug alone.
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