For Hypertension ADULT PATIENTS: The antihypertensive efficacy of amlodipine was demonstrated in 15 double-blind, randomized, placebo-controlled studies of 800 people in the amlodipine group and 538 people in the placebo group. Placebo-corrected, patients with mild-to-moderate hypertension treated with once-daily administration of the drug experienced statistically significant reductions in prone and standing blood pressure 24 hours after dosing, with mean reductions in standing blood pressure of 12/6 mm Hg and in prone blood pressure of 13/7 mm Hg. 24-hour intervals between dosing were observed to allow for a 24-hour persistence of the drug's antihypertensive effects (with peak and trough antihypertensive effects being virtually identical). Tolerance to the drug was not demonstrated in patients who had been on the drug for 1 year. 3 parallel, fixed-dose dose-response studies showed dose-related reductions in prone and standing blood pressure within the recommended dose range. The drug had a similar effect on diastolic blood pressure in young and elderly patients. The greater effect on systolic blood pressure in elderly patients may be related to their higher baseline systolic blood pressure. The effects on black and white populations were similar. Pediatric Patients; 268 hypertensive patients aged 6 to 17 years were first randomized to receive amlodipine 2.5 or 5 mg once daily for 4 weeks and then re-randomized to receive the same dose of amlodipine or placebo for 4 weeks. At the end of 8 weeks, blood pressure was lower in patients receiving 5 mg of amlodipine than in patients randomized again to placebo. The intensity of the drug's antihypertensive effect is difficult to quantify, but the systolic blood pressure drop was less than 5 mm Hg with the 5-mg dose.Adverse events were similar to those in adults. For Chronic Stable Angina: The role of amlodipine, 5-10 mg/day, in exercise-induced angina has been evaluated in eight placebo-controlled, double-blind, clinical studies of 6-week duration*** comprising 1,038 patients with chronic stable angina (684 on amlodipine tablets and 354 on placebo). In five of the studies, a 10mg dose was applied and their exercise (pedaling or activity plate) time was significantly increased. The mean increase in symptom-limited activity time was 12.8% (63 seconds) as well as 7.9% (38 seconds) for amlodipine 10mg versus 5mg, respectively. In some studies, amlodipine 10mg also prolonged the time to 1mm ST-segment excursion and reduced the frequency of angina attacks. The long-lasting efficacy of amlodipine has been demonstrated in long-term studies in patients with angina pectoris. Reductions in blood pressure (4/1 mmHg) and changes in heart rate (+0.3 bpm) were not clinically significant in patients with angina pectoris. Effect on Vasospastic Angina: In a double-blind, placebo-controlled clinical study lasting 4 weeks and including 50 patients, amlodipine treatment was able to reduce anginal episodes by approximately 4 episodes/week, and the placebo group was able to reduce anginal episodes by approximately 1 apoplexy (p<0.01). Patients who withdrew from the study due to insufficient improvement in clinical symptoms were 2/23 in the loxapro group and 7/27 in the placebo group. Role in proven coronary artery disease: The PREVENT study enrolled 825 patients with angiographically proven coronary artery disease who were randomized to amlodipine (5-10 mg once daily) or placebo and followed for 3 years. Although this study did not detect significant changes in the primary endpoint of coronary artery lumen diameter by coronary angiography, the data showed a trend toward a reduction in the proportion of patients with coronary artery disease who were admitted to the hospital for angina episodes and the proportion who required coronary revascularization. The CAMELOT study enrolled 1318 patients with recently confirmed coronary artery disease by angiography, with no lesions in the left main branch of the coronary artery, not accompanied by ejection fraction <40% or heart failure. Patients (76% male, 89% Caucasian, 93% American, 89% with a history of angina pectoris, 52% without PCI, 4% with PCI but no stenting, and 44% with stenting) were randomly assigned to a double-blind treatment group that was treated with a combination of anticoagulants in the standard treatment (of which they received aspirin 89% of the time, statins 83% of the time, β-blockers 74% of the time, nitroglycerin 50% of the time, anticoagulants 40%, diuretics 32%, but excluding other calcium channel antagonists) received either loxapro 5-10 mg/day treatment or placebo on top of standard treatment. The mean duration of follow-up was 19 months. The time of the patient's first one of the following events was the primary endpoint: angina admission; coronary artery revascularization; myocardial infarction; cardiovascular death; cardioversion; heart failure admission; stroke/TIA; or peripheral vascular disease. There were 110 (16.6%) and 151 (23.1%) first events in the amlodipine and placebo groups, respectively, with a risk ratio of 0.691 (95% CI: 0.540-0.884, p=0.003). A summary of the primary endpoints is shown in Figure 1.The conclusions of this study are mainly derived from the preventive effect of the drugs on hospital admissions due to angina episodes, and on coronary revascularization (see Table 1). Figure 2 shows the effects of the different subgroups. In the CAMELOT study subgroup, where coronary angiography was performed (274 cases), amlodipine did not reduce coronary plaque volume (intravascular ultrasound) compared to placebo. Figure 1: Kaplan-Meier Analysis of Composite Clinical Endpoints in the Amlodipine Group vs. Placebo Group Clinical outcomes for the various primary endpoints that were significant are summarized in Table 1 below, Other primary endpoints included cardiovascular death, cardiac resuscitation, myocardial infarction, heart failure admissions, stroke/TIA, or peripheral vascular disease, which were not significantly different in the amlodipine group compared to the placebo group. Studies in Patients with Heart Failure Amlodipine benzenesulfonate was compared to placebo in four 8- to 12-week studies that included 697 patients with NYHA class II/III heart failure. There was no evidence of worsening of heart failure with amlodipine besylate, as measured by exercise tolerance, NYHA class, clinical symptoms, or left ventricular ejection fraction. In a long-term (follow-up of at least 6 months, mean 13.8 months), placebo-controlled, morbidity/mortality study of amlodipine benzenesulfonate, 1,153 patients with NYHA class III (n=931) or NYHA class IV (n=222) heart failure received amlodipine benzenesulfonate 5-10 mg on top of stabilized doses of diuretics, digoxin, and ACEI. Amlodipine benzenesulfonate had no effect on the primary endpoint of the study, NYHA classification, or heart failure symptoms. These composite endpoints were all-cause mortality and cardiovascular morbidity (specifically fatal arrhythmia, acute myocardial infarction, or hospital admission for heart failure exacerbation). In the amlodipine benzenesulfonate group versus the placebo group, the total number of all-cause deaths as well as cardiovascular events was 222/571 (39%) versus 246/583 (42%), respectively, and cardiovascular events accounted for approximately 25% of the study endpoint events in the study. In another randomized study (PRAISE-2), NYHA III (80%) or IV (20%) patients with heart failure without clinical symptoms or definite ischemic disease received placebo (n=827) or amlodipine (n=827) on top of stable doses of ACEI (99%), digitalis (99%), and diuretics (99%). At a mean follow-up of 33 months, the primary endpoint of all-cause mortality was not significantly different in the product as well as the placebo groups (95% confidence intervals, ranging from an 8% decrease to a 29% increase in the amlodipine group). However, more pulmonary edema was reported in the amlodipine group.