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Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis - CAMELOT
Description:
CAMELOT was a multicenter, double-blinded, placebo-controlled randomized trial that sought to study the effects of amlodipine or enalapril compared to placebo in normotensive patients with coronary artery disease.
Hypothesis:
Treatment with amlodipine would be associated with a lower incidence of adverse cardiovascular events compared with placebo.
Study Design
Study Design:
Patients Screened: 2865
Patients Enrolled: 1991
Mean Follow Up: 2 years
Mean Patient Age: mean 58 years
Female: 25
Patient Populations:
Men and women, age 30-79, requiring coronary angiography for evaluation for chest pain or percutaneous coronary intervention, and with diastolic pressure <100 mm Hg, with or without treatment. Angiographic inclusion criteria required 1 or more lesions in a native coronary artery with >20% stenosis by visual estimation.
Exclusions:
Patients with a left main coronary artery obstruction > 50%, left ventricular ejection fraction <40%, or moderate to severe congestive heart failure.
Primary Endpoints:
Adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and any new diagnosis of peripheral vascular disease) for the comparison of amlodipine vs. placebo.
Secondary Endpoints:
Incidence of adverse events for enalapril treatment compared with placebo and comparison of the amlodipine treatment group with the enalapril group. Additional prespecified secondary end points included all-cause mortality and the incidence of revascularization in vessels that had undergone previous stent placement.
The end point for the IVUS substudy was the change in percent atheroma volume for all slices of anatomically comparable segments of the target coronary artery from baseline to 24 months.
Drug/Procedures Used:
ACE inhibitors, angiotensin receptor blockers, and calcium channel blockers were discontinued over a 2-6-week period and were prohibited during the study (with the exception of study medications). During this run-in period, patients were given placebo. Patients demonstrating >80% compliance with placebo were then randomized to take Amlodipine 5 mg qd + placebo Enalapril, Enalapril 10 mg + placebo Amlodipine, or placebo Amlodipine + placebo Enalapril. Study drug doses were doubled after two weeks.
Concomitant Medications:
Standard treatment. Treatment with beta-blockers, alpha-1 blockers, and diuretics were permitted.
Principal Findings:
1991 patients were enrolled, and 274 patients completed the intravascular ultrasound (IVUS) stubstudy. There were only minor differences between the patients in each of the study groups. There were relatively low rates of crossover between study medication classes between the study arms (<8% for both active treatment arms). 18% of patients had diabetes, the mean LDL cholesterol was approximately 102 mg/dL, and the mean systolic blood pressure was 129 mm Hg, with a mean diastolic blood pressure of 78 mmHg. Overall, the study medications were well-tolerated.
Over the follow-up period, the mean blood pressure decreased 4.8/2.5 mmHg in the amlodipine group, 4.9/2.4 mmHg in the enalapril group, and increased 0.7/0.6 mmHg in the placebo group (p<0.001 for both treatment groups vs. placebo). Cardiovascular events occurred less frequently in the amlodipine group (16.6%) compared to both enalapril (20.2%, HR 0.81 for amlodipine vs. enalapril, p=0.1) and placebo (23.1%; HR 0.69 for amlodipine vs. placebo, p=0.003; HR=0.85 for enalapril vs. placebo, p=0.16). The largest component of the reduction in events in the amlodipine arm was in a reduction in coronary revascularization and hospitalization from angina.
In the patients undergoing IVUS, the change in percent atheroma volume from baseline was 3.9% in the amlodipine group, 3.7% in the enalapril group, and 4.4% in the placebo group, with no statistically significant differences between the three groups. Within each group, there was no significant change from baseline in the amlodipine group (p=0.31), a trend towards progression from baseline in the enalapril group (p=0.08), and progression of atheroma from baseline in the placebo group (p=0.001).
Interpretation:
In this multicenter, randomized clinical trial of amlodipine, enalapril, or placebo among patients with coronary artery disease and relatively normal blood pressures, treatment with amlodipine was associated with a reduction in the composite endpoint of cardiovascular events compared to placebo, largely driven by a reduction in coronary revascularization and hospitalization from angina. These reductions were not seen with enalapril, despite a similar reduction in blood pressure, but may reflect the potent anti-anginal effects of amlodipine. For example, when “harder” clinical endpoints were considered (death, non-fatal myocardial infarction, and non-fatsl stroke), amlodipine and enalapril demonstrated similar but not statistically significant reductions in these endpoints compared to placebo.
Nonetheless, this study is the first to demonstrate the beneficial effects of a strategy of treating largely normotensive patients with anti-hypertensive therapy, and in addition provides the IVUS correlate of trends toward reduced atheroma progression with these therapies. These changes were observed on top of adequate medical regimens and lipid control (>90% aspirin, >80% statins). Further confirmatory studies are needed before blood pressure guidelines should be modified, but it appears from this study that “lower is better” may not only apply to lipid-lowering.
References:
Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA 2004;292:2217-25.
Keywords: Angiotensin Receptor Antagonists, Coronary Artery Disease, Myocardial Infarction, Enalapril, Stroke, Plaque, Atherosclerotic, Cholesterol, LDL, Blood Pressure, Constriction, Pathologic, Calcium Channel Blockers, Percutaneous Coronary Intervention, Coronary Angiography, Chest Pain, Amlodipine, Hospitalization, Diabetes Mellitus
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