Long Term Efficacy and Safety of Carvedilol, a New β-Blocking Agent with Vasodilating Properties, in Patients with Chronic Ischaemic Heart Disease

Abstract

The long term efficacy and safety of Carvedilol, a new vasodilating β-blocking drug, was evaluated in 32 patients with chronic stable angina, using a randomised double-blind, placebo-controlled protocol for 1 month, followed by an open phase of 5 months during which all patients received Carvedilol 25mg twice daily. Treadmill exercise testing was performed at the end of 1 (double-blind), 3 and 6 months (open phase). Five patients were withdrawn from the study, 2 because of adverse events and the rest because of noncompliance or surgical intervention during the study. Exercise time (mean ± SD) had improved significantly on Carvedilol at the end of the double-blind phase (1 month) from 6.6 ± 0.6 to 7.7 ± 0.7 min (p < 0.05) and this was maintained at 3 and 6 months (8.3 ± 0.7 min, p < 0.01 and 8.5 ± 0.7 min, p < 0.005, respectively). In the group started on placebo, exercise time also improved significantly from 6.4 ± 0.5 to 7.3 ± 0.5 min (p < 0.05), but this was further improved at 3 (8.0 ± 0.7 min) and 6 months (8.9 ± 0.8 min) with Carvedilol (p < 0.02 and p < 0.0001, respectively). Time to 1mm ST-segment depression did not alter significantly with placebo (4.8 ± 0.6 to 4.9 ± 0.4 min), but was significantly improved by Carvedilol at 1, 3 and 6 months (p < 0.05, p < 0.01 and p < 0.005, respectively). Similarly, time to development of angina during exercise did not alter with placebo (5.1 ± 0.4 to 5.4 ± 0.4 min), but was significantly increased by Carvedilol at 1 month (5.4 ± 0.4 to 6.3 ±0.6 min, p < 0.02), and this was maintained on long term therapy at 3 and 6 months (6.3 ±0.5 min, p < 0.005, and 6.9 ± 0.5 min, p < 0.001, respectively). Peak exercise heart rate and double product were reduced by active therapy only, at 1 month (124 ± 5 to 107 ± 3 beats/minute, p < 0.0001; 197 ± 11 to 160 ± 9, p < 0.0001), 3 months (108 ± 4, p < 0.0001; 162 ± 9, p < 0.001) and 6 months (108 ± 3, p < 0.0005; 157 ± 7, p < 0.0002), respectively. These results suggest that Carvedilol is a well tolerated and effective β-blocker; however, the lack of any significant difference in exercise time with placebo suggests that the dose of 25mg twice daily is insufficient in the management of chronic stable angina.