prevention of acute coronary events with lovasta急性冠脉事件的一级预防与课件

Primary Prevention of Acute Coronary Events with Lovastatin in Men and Women with Average Cholesterol Levels Results of AFCAPS/TexCAPS John R. Downs, Michael Clearfield, Stephen Weis, Edwin Whitney, Deborah R. Shapiro, Polly A. Beere, Alexandra Langendorfer, Evan A. Stein, William B. Kruyer, Antonio M. Gotto; for the AFCAPS/TexCAPS Research Group JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Major Statin Trials LDL-CLDL-C 1 Prevention1 Prevention2 Prevention2 Prevention AFCAPS/AFCAPS/ TexCAPSTexCAPS 4S4SWOSCOPSWOSCOPS CARECARE LIPIDLIPID Gotto, et. al. AHA Nov 97 Preliminary ResultsGotto, et. al. AHA Nov 97 Preliminary Results Objective To compare lovastatin with placebo for prevention of the first acute major coronary event: -unstable angina, fatal and non-fatal MI and sudden cardiac death in a cohort of men and women without clinically evident atherosclerotic CVD, who have average TC and LDL-C and below-average HDL-C. JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 AFCAPS/TexCAPS Study Design Design: -Randomized, double-blind, placebo-controlled trial Setting: -Outpatient clinics in Texas Participants: -5608 men and 997 women with at baseline, average TC (221 mg/dL) and LDL-C (150 mg/dL) and below-average HDL-C (37 mg/dL). Intervention: -Lovastatin (20-40 mg daily - to achieve an LDL-C of 90% stenosis in major epicardial coronary artery.cardiac catheterization: 90% stenosis in major epicardial coronary artery. JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Fatal or Non-Fatal Coronary Fatal or Non-Fatal Coronary RevascularizationRevascularization Fatal or Non-Fatal MIFatal or Non-Fatal MI Unstable AnginaUnstable Angina Fatal or Non-Fatal Cardiovascular Fatal or Non-Fatal Cardiovascular EventsEvents Fatal or Non-Fatal Coronary EventsFatal or Non-Fatal Coronary Events Cardiovascular MortalityCardiovascular Mortality CHD MortalityCHD Mortality Secondary Endpoints JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Total MortalityTotal Mortality Non-Cardiovascular MortalityNon-Cardiovascular Mortality Fatal and Non-Fatal CancerFatal and Non-Fatal Cancer Discontinuation of Medication Discontinuation of Medication because of Adverse Effectsbecause of Adverse Effects Tertiary Endpoints JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Baseline Demographics AFCAPS/TexCAPS NHANES III* Gender Women ( 997) 15% 42% Race White - 89% 85% Hispanic - 7% 7% Black - 3% 8% Mean Age 58 + 7 y.o.60 + 8 y.o. Men (45-73) 57 + 7 y.o. 57 + 8 y.o. Women (55-73)63 + 5 y.o.64 + 5 y.o. 65 at Randomization 21% 33% JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Risk Factors AFCAPS/TexCAPS NHANES III* Hypertension 22% 35% Active Smoker13% 26% NIDDM 2% 4% Family History15% 9% HDL-C Median Median by Ageby Age N=3180N=3180 SmokersSmokers N=818N=818 HypertensionHypertension N=1448N=1448 DiabetesDiabetes N=156N=156 Lovastatin Reduced the Risk of First Acute Major Coronary Events in All Baseline LDL Tertiles Baseline LDL TertilesBaseline LDL Tertiles Poster Presentation at the 1998 ACC Meeting, Atlanta GAPoster Presentation at the 1998 ACC Meeting, Atlanta GA AFCAPS/TexCAPS Role of Baseline LDL on Outcomes Baseline LDL Level (mg/dL)Baseline LDL Level (mg/dL) JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 AFCAPS/TexCAPS Role of Baseline HDL on Outcomes JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 AFCAPS/TexCAPS Role of Baseline HDL on Outcomes Baseline HDL Level (mg/dL)Baseline HDL Level (mg/dL) JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Secondary Endpoint Analyses Fatal and Non-Fatal MIFatal and Non-Fatal MI N=3304N=3281N=3249N=3214N=3174N=1717 N=3301N=3270N=3237N=3200N=3148N=1692 # At Risk Lovastatin Placebo 0.00 0.01 0.02 0.03 Years of Follow-up 0123455+ years Lovastatin Lovastatin PlaceboPlacebo Cumulative IncidenceCumulative Incidence 40% Risk Reduction40% Risk Reduction (p = 0.002)(p = 0.002) 25% Risk Reduction25% Risk Reduction ( (p = 0.003)p = 0.003) Cardiovascular Events*Cardiovascular Events* N=3304N=3260N=3206N=3147N=3088N=1651 N=3301N=3242N=3187N=3124N=3045N=1615 # At Risk Lovastatin Placebo Cumulative Incidence 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 Years of Follow-up 0123455+ years Lovastatin Lovastatin PlaceboPlacebo N=3304N=3281N=3250N=3217N=3174N=1707 N=3301N=3267N=3240N=3205N=3150N=1678 # At Risk Lovastatin Placebo Years of Follow-up Unstable AnginaUnstable Angina Cumulative Incidence 0.00 0.01 0.02 0.03 0123455+ years Lovastatin Lovastatin PlaceboPlacebo32% Risk Reduction32% Risk Reduction (p = 0.02)(p = 0.02) N=3304N=3264N=3215N=3160N=3106N=1666 N=3301N=3246N=3201N=3141N=3069N=1634 # At Risk Lovastatin Placebo Coronary Events*Coronary Events* Cumulative Incidence 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 Years of Follow-up 0123455+ years Lovastatin Lovastatin PlaceboPlacebo 25% Risk Reduction25% Risk Reduction (p = 0.006)(p = 0.006) JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Coronary RevascularizationsCoronary Revascularizations N=3304N=3277N=3237N=3192N=3148N=1691 N=3301N=3258N=3221N=3174N=3108N=1659 # At Risk Lovastatin Placebo Lovastatin Placebo 0.00 0.01 0.02 0.03 0.04 0.05 Years of Follow-up 0123455+ Years 33% Risk Reduction33% Risk Reduction (p = 0.001)(p = 0.001) Cumulative Incidence JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Placebo Placebo Lovastatin Lovastatin EventEvent n=3301 n=3301 n=3304 n=3304 P-valueP-value Total MortalityTotal Mortality 77 77 80 80 N.S. N.S. CardiovascularCardiovascular 25 25 17 17too few* too few* Non-cardiovascular 52Non-cardiovascular 52 63 63 N.S. N.S. Mortality *Too few for survival analyses*Too few for survival analyses JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Tertiary AnalysisTertiary Analysis Fatal and Non-Fatal Cancer*Fatal and Non-Fatal Cancer* N=3304N=3249N=3188N=3117N=3059N=1626 Lovastatin N=3301N=3234N=3171N=3105N=3043N=1603 Placebo # At Risk Lovastatin Placebo 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 Years of Follow-up 0123455+ years Cumulative Incidence P = NS *Excludes non-melanoma skin cancer*Excludes non-melanoma skin cancer Poster Presentation Poster Presentation 1998 ACC Meeting, Atlanta GA1998 ACC Meeting, Atlanta GA PlaceboPlaceboLovastatinLovastatin n=3301n=3301n=3304n=3304P-valueP-value All Fatal and Non-FatalAll Fatal and Non-Fatal259259252252.75.75 Most Frequently ReportedMost Frequently Reported ProstateProstate108108109109 0.99 0.99 MelanomaMelanoma272714140.040.04 ColonColon20202525.55 .55 LungLung17172222.52.52 LymphomaLymphoma11111212 0.99 0.99 BladderBladder11111212 0.99 0.99 BreastBreast 9 91313.52.52 Cancer JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Safety Laboratory *Consecutive elevations*Consecutive elevations # # Treatment group differences were not significantTreatment group differences were not significant JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Summary of Results Men and women who are free of clinical evidence of atherosclerotic CVD, with average TC and LDL-C but below average HDL-C can obtain significant benefit from LDL-C reduction with lovastatin 20-40 mg/day. Lovastatin 20-40 mg/day, (mean dose 30 mg/day) significantly reduced the risk of: The first acute major coronary event - by 37 % (p 45 years, women 55 years HDL 130 mg/dl JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Conclusions Lovastatin 20-40 mg/day reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C and below- average HDL-C These findings support the inclusion of HDL-C in risk-factor assessment and confirm the benefit of LDL-C reduction to a target goal JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 Conclusions Treatment was beneficial for women, and persons with any active risk factor and appeared to neutralize the risk conferred by HTN, smoking and low HDL JAMA 1998;279:1615-1622JAMA 1998;279:1615-1622 AFCAPS/TexCAPS Implications “Using NHANES III survey data, approximately 8