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CAMELOT:CAMELOT: Study Design Study Design
A Morbidity and Mortality StudyA Morbidity and Mortality StudyA Morbidity and Mortality StudyA Morbidity and Mortality Study
Patients with Patients with documented documented
CAD on CAD on standard-of-care standard-of-care
therapies*therapies*(n=(n=19971997))
Patients with Patients with documented documented
CAD on CAD on standard-of-care standard-of-care
therapies*therapies*(n=(n=19971997))
Clinical events Clinical events (morbidity (morbidity
and mortality)and mortality)
Clinical events Clinical events (morbidity (morbidity
and mortality)and mortality)2 Yr2 Yr2 Yr2 Yr
PlaceboPlaceborun-inrun-in
(2-6 wk)(2-6 wk)
Placebo-controlled, multicenter, randomized, double-blind, Placebo-controlled, multicenter, randomized, double-blind, comparative, parallel trial comparative, parallel trial
Enalapril 10-20 mgEnalapril 10-20 mg
Amlodipine 5-10 mgAmlodipine 5-10 mg
PlaceboPlacebo
PCI indicates percutaneous coronary intervention.
Initial sample size was 3000 patients. This was reduced in an amendment to 2000.*Patients stratified by PCI/stent status.
2
CAMELOT:CAMELOT: Primary End Point 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:CAMELOT: Secondary End Points Secondary End Points
Individual MACE components of the primary end pointIndividual MACE components of the primary end point
Requirement for revascularization in vessels that have undergone Requirement for revascularization in vessels that have undergone stenting at baselinestenting at baseline
All-cause mortalityAll-cause mortality
Correlation between change from baseline in BP and time Correlation between change from baseline in BP and time to first MACEto first MACE
– – Rate of MACE tabulated by categories of mean SBP reductionRate of MACE tabulated by categories of mean SBP reduction
4
PlaceboPlaceborun-inrun-in
(2-6 wk)(2-6 wk)Enalapril 10-20 mgEnalapril 10-20 mg
Amlodipine 5-10 mgAmlodipine 5-10 mg
NORMALISE Substudy of CAMELOT:NORMALISE Substudy of CAMELOT:Study DesignStudy Design
CAMELOT CAMELOT patients patients (n=(n=431431))
CAMELOT CAMELOT patients patients (n=(n=431431))
2 Yr2 Yr2 Yr2 Yr
An IVUS Study of Coronary Artery PlaqueAn IVUS Study of Coronary Artery Plaque
IIVVUUSS
PlaquePlaqueprogression/progression/regressionregression
PlaquePlaqueprogression/progression/regressionregression
PlaceboPlacebo
• Multicenter, randomized, double-blind IVUS substudy of CAMELOT
QQCCAA
IIVVUUSS
QQCCAA
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.
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NORMALISE:NORMALISE: IVUS End Points IVUS End Points
Primary:Primary:
Change from baseline in IVUS percent atheroma volume Change from baseline in IVUS percent atheroma volume (PAV) for all slices of the target vessel(PAV) for all slices of the target vessel
Important secondary:Important secondary:
Change in normalized total atheroma volume (TAV)Change in normalized total atheroma volume (TAV)
6
Age, years 57.2 (9.5) 58.5 (9.9) 57.3 (9.7) 0.02
Male gender 73.0% 71.9% 76.3% 0.16
Caucasian 89.0% 89.3% 89.4% 0.97
BMI 29.7±5.0 29.7±5.5 29.9±5.5 0.72
History of hypertension 60.3% 59.7% 61.4% 0.82
BP, mm Hg 129/78 129/77 130/78 N/A
History of dyslipidemia 84.4% 83.7% 83.0% N/A
LDL-cholesterol, mg/dL 100 (32) 101 (31) 104 (32) 0.04
Diabetes 19.8% 17.5% 17.3% 0.42
Unstable angina† 9.9% 8.3% 8.1% 0.45
Prior bypass surgery 8.2% 6.8% 8.0% 0.59
Prior MI 37.7% 40.3% 37.4% 0.50
Current smoker 27.9% 24.8% 27.0% 0.41
Baseline DataBaseline DataBaseline Characteristics, Mean (SD) or Percentage of PatientsBaseline Characteristics, Mean (SD) or Percentage of PatientsBaseline Characteristics, Mean (SD) or Percentage of PatientsBaseline Characteristics, Mean (SD) or Percentage of Patients
Placebo(n=655)
Enalapril(n=673)
Amlodipine(n=663) P value*
*Analysis of variance *Analysis of variance PP value. value. ††Canadian Cardiovascular Society Class 4.Canadian Cardiovascular Society Class 4.
7
*Analysis of variance *Analysis of variance PP value. value.
Statins 84.3% 81.7% 83.1% 0.46
Diuretics 33.4% 26.8% 32.1% 0.02
Beta-blockers 78.8% 74.7% 74.2% 0.11
Aspirin 95.4% 94.7% 94.4% 0.69
ACEs 12.8% 7.0% 7.4% <0.001
ARBs 2.3% 1.6% 1.7% 0.61
CCBs 12.1% 6.1% 5.0% <0.001
Placebo(n=655)
Enalapril(n=673)
Amlodipine(n=663) P value*
Treatments Received and Concomitant Treatments Received and Concomitant MedicationsMedications
Mean (SD) or Percentage of PatientsMean (SD) or Percentage of PatientsMean (SD) or Percentage of PatientsMean (SD) or Percentage of Patients
Titrated to Full Target Dosage 89.80% 84.30% 86.70% 0.01
Mean (SD) Dose Received, mg N/A 17.4 (3.7) 8.6 (2.0) N/A
Completed Trial 93.7% 92.4% 93.4% 0.62
Discontinued Study Medication 31.1% 35.1% 29.3% 0.07
Treatments ReceivedTreatments ReceivedTreatments ReceivedTreatments Received
Concomitant MedicationsConcomitant Medications(Percentage of Patients)(Percentage of Patients)Concomitant MedicationsConcomitant Medications(Percentage of Patients)(Percentage of Patients)
8
CAMELOT Results—Cumulative Event RatesCAMELOT Results—Cumulative Event Rates
Cu
mu
lati
ve e
ven
ts,
pro
po
rtio
n
Months
0 6 12 18 240
0.25
0.20
0.15
0.10
0.5
PlaceboEnalaprilAmlodipine
No. at riskPlacebo 655 588 558 525 488Enalapril 673 608 572 553 529Amlodipine 663 623 599 574 535
31% 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%31%
9
CAMELOT Results—CAMELOT Results—Primary and Secondary End PointsPrimary and Secondary End PointsAmlodipine vs PlaceboAmlodipine vs Placebo
Major adverse CV eventMajor adverse CV event
Individual components Individual components of the primary end pointof the primary end point
Coronary revascularizationCoronary revascularization
Hospitalization for anginaHospitalization for anginaNonfatal MINonfatal MI
Stroke or TIAStroke or TIA
CV deathCV death
Hospitalization for CHFHospitalization for CHF
Resuscitated cardiac arrestResuscitated cardiac arrest
New onset of PVDNew onset of PVD
Secondary end pointsSecondary end points
Revascularization after baseline stentRevascularization after baseline stent
All-cause mortalityAll-cause mortality
Hazard Ratio (95% CI)Hazard Ratio (95% CI)Risk
ReductionRisk
Reduction P valueP value AmlodipineAmlodipine PlaceboPlacebo
2-year event rates2-year event rates
0.50.5 0.750.75 1.01.0 1.51.5 2.02.0Favors AmlodipineFavors Amlodipine Favors PlaceboFavors Placebo
31%31% 0.0030.003 16.6%16.6% 23.23.1%1%
27%27% 0.030.03 11.8%11.8% 15.7%15.7%
42%42% 0.0020.002 7.7%7.7% 12.8%12.8%NMNM 0.370.37 2.1%2.1% 2.9%2.9%
NMNM 0.150.15 0.9%0.9% 1.8%1.8%
NMNM 0.270.27 0.8%0.8% 0.3%0.3%
NMNM 0.460.46 0.5%0.5% 0.8%0.8%
NMNM 0.040.04 0.0%0.0% 0.6%0.6%
NMNM 0.240.24 0.8%0.8% 0.3%0.3%
51%51% 0.0020.002 4.1%4.1% 7.9%7.9%NMNM 0.820.82 1.1%1.1% 0.9%0.9%
NM=Not meaningful because too few events were reported.
10
CAMELOT Results—CAMELOT Results—Primary and Secondary End PointsPrimary and Secondary End PointsAmlodipine vs EnalaprilAmlodipine vs Enalapril
Major adverse CV eventsMajor adverse CV events
Individual components Individual components of the primary end pointof the primary end point
Coronary revascularizationCoronary revascularization
Hospitalization for anginaHospitalization for angina
Nonfatal MINonfatal MI
Stroke or TIAStroke or TIA
CV deathCV death
Hospitalization for CHFHospitalization for CHF
Resuscitated cardiac arrestResuscitated cardiac arrest
New onset of PVDNew onset of PVD
Hazard Ratio (95% CI)Hazard Ratio (95% CI) AmlodioineAmlodioine EnalaprilEnalapril
2-year event rates2-year event rates
0.50.5 0.750.75 1.01.0 1.51.5 2.02.0Favors AmlodipineFavors Amlodipine Favors EnalaprilFavors Enalapril
19%19% 0.100.10 16.6%16.6%20.2%20.2%
16%16% 0.240.24 11.8%11.8% 14.1%14.1%
41%41% 0.0030.003 7.7%7.7% 12.8%12.8%NMNM 0.490.49 2.1%2.1% 1.6%1.6%
NMNM 0.610.61 0.9%0.9% 1.2%1.2%
NMNM 0.910.91 0.8%0.8% 0.7%0.7%
NMNM 0.740.74 0.5%0.5% 0.6%0.6%
NMNM 0.310.31 0.0%0.0% 0.1%0.1%
NMNM 0.410.41 0.8%0.8% 1.2%1.2%
34%34% 0.090.09 4.1%4.1% 6.2%6.2%
NMNM 0.870.87 1.1%1.1% 1.2%1.2%
Risk Reduction
Risk Reduction P valueP value
Secondary end pointsSecondary end points
Revascularization after baseline stentRevascularization after baseline stent
All-cause mortalityAll-cause mortality
NM=Not meaningful because too few events were reported.
11
NORMALISE Results—NORMALISE Results—IVUS for All Substudy PatientsIVUS for All Substudy Patients
All Patients (n=274)
**PP value by ANCOVA (adjusting for randomization stratum and baseline values as covariates). value by ANCOVA (adjusting for randomization stratum and baseline values as covariates). ††PP value for change from baseline from least square mean using the same ANCOVA model. value for change from baseline from least square mean using the same ANCOVA model.
ANCOVA indicates analysis of covariance.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 withNote: 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 withcoronary intervention for the ANCOVA model.coronary intervention for the ANCOVA model.
Placebo(n=95)
Placebo(n=95)
Enalapril(n=88)
Enalapril(n=88)
Amlodipine(n=91)
Amlodipine(n=91)
P value Enalapril vs
placebo*
P value Enalapril vs
placebo*
P value Amlodipine vs
placebo*
P value Amlodipine vs
placebo*
P value Enalapril vs Amlodipine*
P value Enalapril vs Amlodipine*
Baseline percent atheroma volumeBaseline percent atheroma volume
Mean (SD)Mean (SD) 42.142.1 41.641.6 39.939.9 0.750.75 0.140.14 0.250.25(9.3)(9.3) (9.8)(9.8) (10.5)(10.5)
Follow-up percent atheroma volumeFollow-up percent atheroma volume
Mean (SD)Mean (SD) 43.443.4 42.442.4 40.440.4 0.500.50 0.050.05 0.200.20(9.6)(9.6) (10.4)(10.4) (10.8)(10.8)
Change in percent atheroma volumeChange in percent atheroma volume
Mean (SD)Mean (SD) 1.31.3 0.80.8 0.50.5 0.320.32 0.120.12 0.590.59(4.4)(4.4) (3.7)(3.7) (3.9)(3.9)
PP value compared value compared with baselinewith baseline†† 0.0010.001 0.080.08 0.310.31
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Results—Summary Results—Summary
Amlodipine reduced: Amlodipine reduced: – The primary end point, major adverse CV event, by 31%The primary end point, major adverse CV event, by 31%– Hospitalization for angina by 42% vs placeboHospitalization for angina by 42% vs placebo
And 41% vs enalaprilAnd 41% vs enalapril
– Coronary revascularization by 27% Coronary revascularization by 27% – Enalapril was not statistically different vs placeboEnalapril was not statistically different vs placebo
IVUS results demonstrate that Amlodipine appears toIVUS results demonstrate that Amlodipine appears toslow atherosclerotic progressionslow atherosclerotic progression