Haffner SM, Alexander CM, Cook TJ, Boccuzzi SJ, Haffner SM, Alexander CM, Cook TJ, Boccuzzi SJ, Musliner TA, Pedersen TR, Kjekshus J, Pyorala K for Musliner TA, Pedersen TR, Kjekshus J, Pyorala K for the 4S Group the 4S Group Reduced Coronary Events in Simvastatin-Treated Subjects with CHD and Diabetes or Impaired Fasting Glucose: Subgroup Analyses in the Scandinavian Simvastatin Survival Study Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Expanded 4S Diabetes AnalysisDiabetes Mellitus by HistoryDiabetes Mellitus by History 202 Subjects (Original 4S Diabetes Subgroup)202 Subjects (Original 4S Diabetes Subgroup)FG 126 mg/dl, but No History of DiabetesFG 126 mg/dl, but No History of Diabetes 281 Subjects281 SubjectsImpaired Fasting Glucose (FG 110-125 mg/dl)Impaired Fasting Glucose (FG 110-125 mg/dl) 678 Subjects678 SubjectsNormal (FG 110 mg/dl)Normal (FG 126 126 mg/dl)mg/dl)New Category of IFG (FG 110-125 mg/dl)(FG 110-125 mg/dl)GoalsConfirm previous dataPerform analysis of 4S subjects with IFGHaffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Baseline CharacteristicsNormalNormalIFGIFGDM-FGDM-FGDM - HxDM - Hxn n32373237678678281281202202AgeAge5959595959596060Male (%)Male (%)8080848489897878SBPSBP138138139139141141147147Tot-CTot-C261261261261261261259259LDL-CLDL-C189189189189186186189189HDL-CHDL-C4646454544444444TGTG130130137137142142153153FGFG9595117117136136175175Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Percent Change in Lipids and Lipoproteins in 4SHaffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Incidence of Major CHD Events by Glucose Status in the 4S Placebo GroupNFGNFG(n=1631)(n=1631)IFGIFG(n=335)(n=335)DM-FGDM-FG(n=135)(n=135)DM-historyDM-history(n=97)(n=97)Baseline Glucose StatusBaseline Glucose StatusHaffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-26674S Major Coronary Heart Disease EventsRR =RR = 0.68 0.68 0.62 0.62 0.580.58p value = 0.001p value = 0.001 0.003 0.003 0.0010.001n =n = 1631/1606 1631/1606 335/343 335/343 232/251232/251Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-26674S & RevascularizationsRR =RR = 0.67 0.67 0.57 0.57 0.520.52p value = 0.001p value = 0.001 0.01 0.01 0.0050.005n =n = 1631/1606 1631/1606 335/343 335/343 232/251232/251Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-26674S Total MortalityRR =RR = 0.72 0.72 0.57 0.57 0.790.79p value = 0.005p value = 0.005 0.02 0.02 0.340.34n =n = 1631/1606 1631/1606 335/343 335/343 232/251232/251Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667IFG Subjects (n=678)IFG Subjects (n=678)0.00.00.20.20.40.40.60.60.80.81.01.01.21.21.41.4Relative RiskRelative RiskMCEMCERevascularizationRevascularizationTot MortalityTot MortalityCHD MortalityCHD Mortalityp=0.003p=0.003p=0.009p=0.009p=0.02p=0.02p=0.007p=0.0070.620.620.570.570.570.570.450.45Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Diabetic Subjects (n=483)Diabetic Subjects (n=483)0.00.20.40.60.81.01.21.4Relative RiskMCERevascularizationTot MortalityCHD Mortalityp=0.001p=0.005p=0.34p=0.260.580.520.790.72Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667 Major CHD EventsMajor CHD EventsNFG SimvastatinNFG SimvastatinNFG PlaceboNFG PlaceboIFG SimvastatinIFG SimvastatinIFG PlaceboIFG PlaceboDM SimvastatinDM SimvastatinDM PlaceboDM PlaceboArch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Effects of Simvastatin on Major Coronary Events by Glucose Status Stratified by Level of Lipid ParametersArch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Absolute and Relative Risk Benefit of Simvastatin Therapy by Glucose Status for Major Coronary EventsNFGNFGIFGIFGDMDMSimvastatin group, No. (%)Simvastatin group, No. (%) 299/1606 (18.6) 67/343 (19.5) 59/251 (23.5) 299/1606 (18.6) 67/343 (19.5) 59/251 (23.5)Placebo group, No. (%)Placebo group, No. (%) 428/1631 (26.2) 102/335 (30.5) 87/232 (37.5) 428/1631 (26.2) 102/335 (30.5) 87/232 (37.5)Relative risk Relative risk 0.680.680.620.620.580.58P relative riskP relative risk0.0010.0010.0030.0030.0010.001Absolute benefit (Kaplan-Meier yearAbsolute benefit (Kaplan-Meier year 6 estimate) 6 estimate) 8.02/100 cases 12.11/100 cases 13.85/100 cases 8.02/100 cases 12.11/100 cases 13.85/100 casesNumber needed to treatNumber needed to treat12128 87 7Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Summary - Diabetes MellitusSummary - Diabetes MellitusHigher event rate in diabetes group, by history, compared to other groupsIn combined DM group (by history and fasting glucose):Major Coronary Events were reduced by 42% (p=0.001)Revascularizations were reduced by 48% (p=0.005)Total and coronary mortality were reduced, but reductions not significant due to small sample sizeHaffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667Summary - Impaired Fasting GlucoseSummary - Impaired Fasting GlucoseReduced total mortality by 43% (p=0.02) Reduced coronary mortality by 55% (p=0.007) Reduced major coronary events by 38% (p=0.003)Reduced the need for revascularization procedures by 43% (p=0.009)Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667ConclusionsConclusionsThis analysis confirms and extends the benefit of cholesterol lowering with simvastatin in an expanded cohort of patients with diabetes and overt CHDCHD patients with impaired fasting glucose (FG 110 to 125 mg/dL) benefit from treatment with simvastatin by significant & substantial reductions in total and coronary mortality, major CHD events and revascularizations.Haffner SM, et al. Haffner SM, et al. Arch Intern MedArch Intern Med 1999;159:2661-2667 1999;159:2661-2667