of revascularization procedures(see Table 1). Effects in various subgroups are shown in Figure 2.In an angiographic substudy (n=274) conducted within CAMELOT, there was no significantdifference between amlodipine and placebo on the change of atheroma volume in the coronaryartery as assessed by intravascular ultrasound.
Figure 1 - Kaplan-Meier Analysis of Composite Clinical Outcomes for Amlodipine versus
Placebo
Figure 2 – Effects on Primary Endpoint of Amlodipine versus Placebo across Sub-Groups
Table 4 below summarizes the significant composite endpoint and clinical outcomes from thecomposites of the primary endpoint. The other components of the primary endpoint includingcardiovascular death, resuscitated cardiac arrest, myocardial infarction, hospitalization for heartfailure, stroke/TIA, or peripheral vascular disease did not demonstrate a significant differencebetween amlodipine and placebo.
Table 4. Incidence of Significant Clinical Outcomes
Clinical Outcomes
N (%)
Amlodipine
(N=663)
Placebo
(N=655)
Risk Reduction
(p-value)
Composite CV Endpoint 110
(16.6)
151
(23.1)
31%
(0.003)
Hospitalization for Angina* 51
(7.7)
84
(12.8)
42%
(0.002)
Coronary Revascularization* 78
(11.8)
103
(15.7)
27%
(0.033)
* Total patients with these events
14.5 Studies in Patients with Heart FailureAmlodipine has been compared to placebo in four 8–12 week studies of patients with NYHAClass II/III heart failure, involving a total of 697 patients. In these studies, there was no evidenceof worsened heart failure based on measures of exercise tolerance, NYHA classification,
symptoms, or left ventricular ejection fraction. In a long-term (follow-up at least 6 months,mean 13.8 months) placebo-controlled mortality/morbidity study of amlodipine 5–10 mg in1153 patients with NYHA Classes III (n=931) or IV (n=222) heart failure on stable doses ofdiuretics, digoxin, and ACE inhibitors, amlodipine had no effect on the primary endpoint of thestudy which was the combined endpoint of all-cause mortality and cardiac morbidity (as definedby life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heartfailure), or on NYHA classification, or symptoms of heart failure. Total combined all-cause
mortality and cardiac morbidity events were 222/571 (39%) for patients on amlodipine and246/583 (42%) for patients on placebo; the cardiac morbid events represented about 25% of theendpoints in the study.
In another study, (PRAISE-2) randomized patients with NYHA Class III (80%) or IV (20%)heart failure without clinical symptoms or objective evidence of underlying ischemic disease, onstable doses of ACE inhibitors (99%), digitalis (99%), and diuretics (99%), to placebo (n=827)or amlodipine (n=827) and followed them for a mean of 33 months. There was no statisticallysignificant difference between amlodipine and placebo in the primary endpoint of all-causemortality (95% confidence limits from 8% reduction to 29% increase on amlodipine). Withamlodipine there were more reports of pulmonary edema.
16 HOW SUPPLIED/STORAGE AND HANDLING
KATERZIA (amlodipine) is a white to off-white, aqueous oral suspension that contains 1 mg ofamlodipine per milliliter (equivalent to 1.30 mg of amlodipine benzoate). It is supplied as 150mL in a 185 mL high-density polyethylene (HDPE) bottle with a child-resistant cap and tamperevidentseal. SHAKE BEFORE USI |
