Safety of Controlled-onset Extended-release Verapamil
Safety of Controlled-onset Extended-release Verapamil
Background. Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients.
Methods. Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (
65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test.
Results. In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup.
Conclusion. These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.
For cardiovascular diseases, in which the duration of therapy is indefinite, the issue of drug tolerability and safety becomes an important factor determining whether a patient will remain adherent to therapy. This is especially true for hypertension, a disease that often has no overt symptoms. Because hypertension and chronic stable angina pectoris have such a broad impact on risk for cardiovascular events, implementation of successful treatment programs in affected patients is critical. Enhanced drug tolerability and patient satisfaction with treatment may improve adherence to regimens for these diseases and thus improve long-term cardiovascular outcomes.
Patients with poorly controlled blood pressure tend to have a higher incidence of most side effects than do those with well-controlled blood pressure. Moreover, poor medication adherence among hypertensive patients also increases health care utilization and costs. Because patients >65 years old may have altered pharmacokinetics of certain medications (delayed clearance, longer half-lives), they may be more prone to enhanced efficacy or increased incidence of adverse events. Therefore clinical trials of new drug agents should specifically assess drug safety in the elderly, and agents chosen for these patients should be those that are safe and well tolerated. There is a general lack of well-controlled studies evaluating differences in the occurrence of adverse events between elderly and younger populations treated with antihypertensive and antianginal medications.
For these reasons, the current analysis was undertaken to evaluate the safety and tolerability of a chronotherapeutic formulation of a calcium antagonist controlled-onset, extended-release (COER) verapamil in patients with hypertension or angina. Because verapamil has the potential for specific cardiac effects, we especially investigated safety in elderly patients.
Background. Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients.
Methods. Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (
65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test.
Results. In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup.
Conclusion. These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.
For cardiovascular diseases, in which the duration of therapy is indefinite, the issue of drug tolerability and safety becomes an important factor determining whether a patient will remain adherent to therapy. This is especially true for hypertension, a disease that often has no overt symptoms. Because hypertension and chronic stable angina pectoris have such a broad impact on risk for cardiovascular events, implementation of successful treatment programs in affected patients is critical. Enhanced drug tolerability and patient satisfaction with treatment may improve adherence to regimens for these diseases and thus improve long-term cardiovascular outcomes.
Patients with poorly controlled blood pressure tend to have a higher incidence of most side effects than do those with well-controlled blood pressure. Moreover, poor medication adherence among hypertensive patients also increases health care utilization and costs. Because patients >65 years old may have altered pharmacokinetics of certain medications (delayed clearance, longer half-lives), they may be more prone to enhanced efficacy or increased incidence of adverse events. Therefore clinical trials of new drug agents should specifically assess drug safety in the elderly, and agents chosen for these patients should be those that are safe and well tolerated. There is a general lack of well-controlled studies evaluating differences in the occurrence of adverse events between elderly and younger populations treated with antihypertensive and antianginal medications.
For these reasons, the current analysis was undertaken to evaluate the safety and tolerability of a chronotherapeutic formulation of a calcium antagonist controlled-onset, extended-release (COER) verapamil in patients with hypertension or angina. Because verapamil has the potential for specific cardiac effects, we especially investigated safety in elderly patients.