Presentation on theme: "1 CAMELOT: Study Design A Morbidity and Mortality Study Patients with documented CAD on standard-of-care therapies* (n=1997) Clinical events (morbidity."— Presentation transcript:
1 CAMELOT: Study Design A Morbidity and Mortality Study Patients with documented CAD on standard-of-care therapies* (n=1997) Clinical events (morbidity and mortality) 2 Yr Placebo run-in (2-6 wk) Placebo-controlled, multicenter, randomized, double-blind, comparative, parallel trial Enalapril mg Amlodipine 5-10 mg Placebo PCI indicates percutaneous coronary intervention. Initial sample size was 3000 patients. This was reduced in an amendment to *Patients stratified by PCI/stent status.
2 CAMELOT: Primary End Point Time to first composite major CV event (MACE): CV death Nonfatal MI Resuscitated cardiac arrest Need for coronary revascularization Hospitalization for: – –Angina – –CHF – –PVD procedure Stoke (fatal or nonfatal) or TIA PVD (new diagnosis) PVD indicates peripheral vascular disease; and TIA, transient ischemic attack.
3 CAMELOT: Secondary End Points Individual MACE components of the primary end point Requirement for revascularization in vessels that have undergone stenting at baseline All-cause mortality Correlation between change from baseline in BP and time to first MACE – Rate of MACE tabulated by categories of mean SBP reduction
4 Placebo run-in (2-6 wk) Enalapril mg Amlodipine 5-10 mg NORMALISE Substudy of CAMELOT: Study Design CAMELOT patients (n=431) 2 Yr An IVUS Study of Coronary Artery Plaque IVUSIVUSIVUSIVUS Plaque progression/ regression regression Placebo Multicenter, randomized, double-blind IVUS substudy of CAMELOT QCAQCAQCAQCA IVUSIVUSIVUSIVUS QCAQCAQCAQCA N = 274 Initial sample size was 750 patients. This was reduced in an amendment to 360, after 431 patients had undergone their initial IVUS. Ultimately, 274 patients received their second IVUS.
5 NORMALISE: IVUS End Points Primary: Change from baseline in IVUS percent atheroma volume (PAV) for all slices of the target vessel Important secondary: Change in normalized total atheroma volume (TAV)
6 Age, years57.2 (9.5)58.5 (9.9)57.3 (9.7)0.02 Male gender73.0%71.9%76.3%0.16 Caucasian89.0%89.3%89.4%0.97 BMI29.7± ± ± History of hypertension60.3%59.7%61.4%0.82 BP, mm Hg129/78129/77130/78N/A History of dyslipidemia84.4%83.7%83.0%N/A LDL-cholesterol, mg/dL100 (32)101 (31)104 (32)0.04 Diabetes19.8%17.5%17.3%0.42 Unstable angina † 9.9%8.3%8.1%0.45 Prior bypass surgery8.2%6.8%8.0%0.59 Prior MI37.7%40.3%37.4%0.50 Current smoker27.9%24.8%27.0%0.41 Baseline Data Baseline Characteristics, Mean (SD) or Percentage of Patients Placebo (n=655) Enalapril (n=673) Amlodipine (n=663) P value* *Analysis of variance P value. † Canadian Cardiovascular Society Class 4.
7 *Analysis of variance P value. Statins84.3%81.7%83.1%0.46 Diuretics33.4%26.8%32.1%0.02 Beta-blockers78.8%74.7%74.2%0.11 Aspirin95.4%94.7%94.4%0.69 ACEs12.8%7.0%7.4%<0.001 ARBs2.3%1.6%1.7%0.61 CCBs12.1%6.1%5.0%<0.001 Placebo (n=655) Enalapril (n=673) Amlodipine (n=663) P value* Treatments Received and Concomitant Medications Mean (SD) or Percentage of Patients Titrated to Full Target Dosage89.80%84.30%86.70%0.01 Mean (SD) Dose Received, mgN/A17.4 (3.7)8.6 (2.0)N/A Completed Trial 93.7%92.4%93.4%0.62 Discontinued Study Medication31.1%35.1%29.3%0.07 Treatments Received Concomitant Medications (Percentage of Patients) Concomitant Medications (Percentage of Patients)
8 CAMELOT Results—Cumulative Event Rates Cumulative events, proportion Months Placebo Enalapril Amlodipine No. at risk Placebo Enalapril Amlodipine % Risk reduction for Amlodipine vs placebo (P=0.003) 19% Risk reduction for Amlodipine vs enalapril (P=0.10) 15% Risk reduction for enalapril vs placebo (P=0.16) 31%
9 CAMELOT Results— Primary and Secondary End Points Amlodipine vs Placebo Major adverse CV event Individual components of the primary end point Coronary revascularization Hospitalization for angina Nonfatal MI Stroke or TIA CV death Hospitalization for CHF Resuscitated cardiac arrest New onset of PVD Secondary end points Revascularization after baseline stent All-cause mortality Hazard Ratio (95% CI) Risk Reduction P value Amlodipine Placebo 2-year event rates Favors Amlodipine Favors Placebo 31% %23. 1% 27% %15.7% 42% %12.8% NM %2.9% NM %1.8% NM %0.3% NM %0.8% NM %0.6% NM %0.3% 51% %7.9% NM %0.9% NM=Not meaningful because too few events were reported.
10 CAMELOT Results— Primary and Secondary End Points Amlodipine vs Enalapril Major adverse CV events Individual components of the primary end point Coronary revascularization Hospitalization for angina Nonfatal MI Stroke or TIA CV death Hospitalization for CHF Resuscitated cardiac arrest New onset of PVD Hazard Ratio (95% CI) Amlodioine Enalapril 2-year event rates Favors Amlodipine Favors Enalapril 19% %20.2% 16% %14.1% 41% %12.8% NM %1.6% NM %1.2% NM %0.7% NM %0.6% NM %0.1% NM %1.2% 34% %6.2% NM %1.2% Risk Reduction P value Secondary end points Revascularization after baseline stent All-cause mortality NM=Not meaningful because too few events were reported.
11 NORMALISE Results— IVUS for All Substudy Patients All Patients (n=274) *P value by ANCOVA (adjusting for randomization stratum and baseline values as covariates). † P value for change from baseline from least square mean using the same ANCOVA model. ANCOVA indicates analysis of covariance. Note: Since there were only 5–7 patients per treatment group in the stent stratum, the stent and non-stent intervention groups were combined into a stratum with coronary intervention for the ANCOVA model. Placebo (n=95) Enalapril (n=88) Amlodipine (n=91) P value Enalapril vs placebo* P value Amlodipine vs placebo* P value Enalapril vs Amlodipine* Baseline percent atheroma volume Mean (SD) (9.3)(9.8)(10.5) Follow-up percent atheroma volume Mean (SD) (9.6)(10.4)(10.8) Change in percent atheroma volume Mean (SD) (4.4)(3.7)(3.9) P value compared with baseline †
12 Results—Summary Amlodipine reduced: –The primary end point, major adverse CV event, by 31% –Hospitalization for angina by 42% vs placebo And 41% vs enalapril –Coronary revascularization by 27% –Enalapril was not statistically different vs placebo IVUS results demonstrate that Amlodipine appears to slow atherosclerotic progression