Effects of Amlodipine
Effects of Amlodipine
Background: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction.
Methods:Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design.
Results:Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 ± 9 (SE) seconds; exercise time for those taking placebo increased 66 ± 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3.4% ± 0.5% in amlodipine-treated patients and 1.5% ± 0.5% in placebo-treated patients (P = .007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups.
Conclusions:The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.
The addition of vasodilating calcium channel blockers to standard therapy in heart failure from left ventricular (LV) systolic dysfunction is conceptually attractive, based on the potential for favorable hemodynamic effects associated with afterload reduction, heart rate lowering effects with certain agents, and the potential for improved coronary blood flow and diastolic function. However, other characteristics, such as the potential for negative inotropic and adverse neurohormonal effects with long-term therapy, may result in unfavorable outcomes. The effects of different calcium channel blocking agents on exercise tolerance in these patients has been inconsistent. Although some studies have shown improvement in treadmill time, unfavorable clinical effects such as worsening heart failure have also been reported.
In a preliminary study with the third-generation calcium channel blocker amlodipine, exercise tolerance over an 8-week period of therapy was found to be improved compared with placebo in conjunction with improvement in symptom status and a favorable effect on neurohormonal profile. On the basis of these preliminary results, larger studies were designed to assess the effect of the addition of the amlodipine to standard therapy in heart failure from LV systolic dysfunction. Thus the objective of these randomized, double-blind, placebo-controlled trials was to determine the effect on exercise time, quality of life, LV function, and safety parameters of adding amlodipine to standard therapy in patients with heart failure.
Background: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction.
Methods:Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design.
Results:Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 ± 9 (SE) seconds; exercise time for those taking placebo increased 66 ± 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3.4% ± 0.5% in amlodipine-treated patients and 1.5% ± 0.5% in placebo-treated patients (P = .007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups.
Conclusions:The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.
The addition of vasodilating calcium channel blockers to standard therapy in heart failure from left ventricular (LV) systolic dysfunction is conceptually attractive, based on the potential for favorable hemodynamic effects associated with afterload reduction, heart rate lowering effects with certain agents, and the potential for improved coronary blood flow and diastolic function. However, other characteristics, such as the potential for negative inotropic and adverse neurohormonal effects with long-term therapy, may result in unfavorable outcomes. The effects of different calcium channel blocking agents on exercise tolerance in these patients has been inconsistent. Although some studies have shown improvement in treadmill time, unfavorable clinical effects such as worsening heart failure have also been reported.
In a preliminary study with the third-generation calcium channel blocker amlodipine, exercise tolerance over an 8-week period of therapy was found to be improved compared with placebo in conjunction with improvement in symptom status and a favorable effect on neurohormonal profile. On the basis of these preliminary results, larger studies were designed to assess the effect of the addition of the amlodipine to standard therapy in heart failure from LV systolic dysfunction. Thus the objective of these randomized, double-blind, placebo-controlled trials was to determine the effect on exercise time, quality of life, LV function, and safety parameters of adding amlodipine to standard therapy in patients with heart failure.
