ents receiving 2.5 mg or 5 mg at the end of 8 weeks hadsignificantly lower systolic blood pressure than those secondarily randomized to placebo. Themagnitude of the treatment effect is difficult to interpret, but it is probably less than 5 mmHgsystolic on the 5 mg dose and 3.3 mmHg systolic on the 2.5 mg dose. Adverse events weresimilar to those seen in adults.
14.2 Effects in Chronic Stable Angina
The effectiveness of 5–10 mg/day of amlodipine in exercise-induced angina has been eva luatedin 8 placebo-controlled, double-blind clinical trials of up to 6 weeks duration involving1038 patients (684 amlodipine, 354 placebo) with chronic stable angina. In 5 of the 8 studies,significant increases in exercise time (bicycle or treadmill) were seen with the 10 mg dose.
Increases in symptom-limited exercise time averaged 12.8% (63 sec) for amlodipine 10 mg, andaveraged 7.9% (38 sec) for amlodipine 5 mg. Amlodipine 10 mg also increased time to 1 mmST segment deviation in several studies and decreased angina attack rate. The sustained efficacyof amlodipine in angina patients has been demonstrated over long-term dosing. In patients withangina, there were no clinically significant reductions in blood pressures (4/1 mmHg) or changesin heart rate (+0.3 bpm).
14.3 Effects in Vasospastic Angina
In a double-blind, placebo-controlled clinical trial of 4 weeks duration in 50 patients, amlodipinetherapy decreased attacks by approximately 4/week compared with a placebo decrease ofapproximately 1/week (p<0.01). Two of 23 amlodipine and 7 of 27 placebo patientsdiscontinued from the study due to lack of clinical improvement.
14.4 Effects in Documented Coronary Artery Disease
In PREVENT, 825 patients with angiographically documented coronary artery disease wererandomized to amlodipine (5–10 mg once daily) or placebo and followed for 3 years. Althoughthe study did not show significance on the primary objective of change in coronary luminaldiameter as assessed by quantitative coronary angiography, the data suggested a favorableoutcome with respect to fewer hospitalizations for angina and revascularization procedures inpatients with CAD.
CAMELOT enrolled 1318 patients with CAD recently documented by angiography, without leftmain coronary disease and without heart failure or an ejection fraction <40%. Patients (76%males, 89% Caucasian, 93% enrolled at US sites, 89% with a history of angina, 52% withoutPCI, 4% with PCI and no stent, and 44% with a stent) were randomized to double-blindtreatment with either amlodipine (5–10 mg once daily) or placebo in addition to standard carethat included aspirin (89%), statins (83%), beta-blockers (74%), nitroglycerin (50%),anti-coagulants (40%), and diuretics (32%), but excluded other calcium channel blockers. Themean duration of follow-up was 19 months. The primary endpoint was the time to firstoccurrence of one of the following events: hospitalization for angina pectoris, coronaryrevascularization, myocardial infarction, cardiovascular death, resuscitated cardiac arrest,hospitalization for heart failure, stroke/TIA, or peripheral vascular disease. A total of
110 (16.6%) and 151 (23.1%) first events occurred in the amlodipine and placebo groups,respectively, for a hazard ratio of 0.691 (95% CI: 0.540–0.884, p = 0.003). The primaryendpoint is summarized in Figure 1 below. The outcome of this study was largely derived fromthe prevention of hospitalizations for angina and the prevention |
