1. Cholesterol-Lowering Therapy in Women and Elderly Patients with Myocardial Infarction or Angina Pectoris Findings From the Scandinavian Simvastatin Survival Study (4S) Tatu A. Miettinen, MD; Kalevi Pyorala, MD; Anders G. Olsson, MD; Thomas A. Musliner, MD; Thomas J. Cook, MD; Ole Faergeman, MD; Kare Berg, MD; Terje Pedersen, MD; John Kjekshsus, MD; for the Scandinavian Simvastatin Survival Study Circulation. 1997;96:4211-4218

2. Women and Elderly in 4S  827 women (age range 35-70 years) who comprised 19% of the total study population (407 in the simvastatin group and 420 in the placebo group).  1021 patients > 65 years of age comprised 23% of the total population (518 in the simvastatin group and 503 in the placebo group). Circulation. 1997;96:4211-4218

3. Women and Elderly Substudy in 4S -Between-Treatment Changes in Lipid Parameters- TCLDLHDLTrigs Circulation. 1997;96:4211-4218

4. Kaplan-Meier Survival Curves for Women and Men in the 4S Trial - Major CHD Event - FemalesMales Circulation. 1997;96:4211-4218 P=0.01P<0.00001

5. Kaplan-Meier Survival Curves for Patients > 65 years of age, and patients 65 years of age, and patients < 65 years of age in the 4S Trial - Major CHD Event - Age < 65 Years Age > Age >  65 Years Circulation. 1997;96:4211-4218 P<0.00001P<0.001 P<0.00001

6. Kaplan-Meier Survival Curves for Women and Men in the 4S Trial - Revascularization - FemalesMales Circulation. 1997;96:4211-4218 P=0.01P<0.00001

7. Kaplan-Meier Survival Curves for Patients > 65 years of age, and patients 65 years of age, and patients < 65 years of age in the 4S Trial - Revascularization - Age < 65 Years Age > Age >  65 Years Circulation. 1997;96:4211-4218 P<0.00001P<0.001

8. Kaplan-Meier Survival Curves for Patients > 65 years of age, and patients 65 years of age, and patients < 65 years of age in the 4S Trial - All Cause Mortality - Age < 65 Years Age > Age >  65 Years Circulation. 1997;96:4211-4218 P<0.01P<0.01

9. Clinical End Points in 4S Subpopulations -Women- Circulation. 1997;96:4211-4218 Number of Patients

10. Clinical Endpoints in 4S Subpopulations - - Women - Circulation. 1997;96:4211-4218 TotalMortalityCHDMortalityMCENonfatalMI Any acute CHD-relatedend-pointeventAnyatherosclerosis-related end-point event Revascularizationprocedure P=0.58 P=0.67 P=0.012 P=0.011 P=0.014P=0.006 P=0.012

11. Women Substudy in 4S Decrease in Hospital Bed Days for all CV 1457 days 2391 days 39% Decrease p < 0.05 Circulation. 1997;96:4211-4218

12. Clinical End Points in 4S Populations -Age >  65 y- Circulation. 1997;96:4211-4218 Number of Patients

13. Clinical Endpoints in 4S Subpopulations - Age >  65 y - Circulation. 1997;96:4211-4218 TotalMortalityCHDMortalityMCENonfatalMI Any acute CHD-relatedend-pointeventAnyatherosclerosis-related end-point event Revascularizationprocedure P=0.009P=0.003P<0.001P=0.004P<0.001P<0.001P=0.003

14. Clinical End Points in 4S Populations -Age <  65 y- Circulation. 1997;96:4211-4218 Number of Patients

15. Clinical Endpoints in 4S Subpopulations - Age <  65 y - Circulation. 1997;96:4211-4218 TotalMortalityCHDMortalityMCENonfatalMI Any acute CHD-relatedend-pointeventAnyatherosclerosis-related end-point event Revascularizationprocedure P=0.007P<0.001P<0.001P<0.001P<0.001P<0.001P<0.001

16. Elderly Substudy in 4S Decrease in Hospital Bed Days for all CV 2776 days 3843 days 28% Decrease p < 0.01 Circulation. 1997;96:4211-4218

17. Discussion - Women  Differences in baseline characteristics for women compared with men in 4S included a lower proportion of prior MI, more nonsmokers, more baseline diagnoses of HTN, greater use of nitrates & CCBs and fewer prior coronary revascularization procedures.  Females were slightly older than males and they had higher HDL levels with comparable LDL levels.  Some of these differences undoubtedly contributed to the lower incidence of CHD mortality and nonfatal CHD events in women compared with men. Circulation. 1997;96:4211-4218

18. Discussion - Women  4S is the first clinical trial to convincingly demonstrate that cholesterol-lowering therapy reduces the risk of major coronary events in women with preexisting CHD.  The magnitude of the reduction (34%) was similar to that observed in men.  Small numbers of CHD and total deaths in women precluded meaningful assessment of simvastatin effects on all-cause or CHD mortality in women. Circulation. 1997;96:4211-4218

19. Discussion - Elderly  The most notable baseline differences between the age subgroups were fewer smokers and greater numbers of patients entered on basis of MI in older versus younger patients  Because of the randomization process, however, between-treatment group differences for the age subpopulations were minor and did not significantly affect the results Circulation. 1997;96:4211-4218

20. Discussion - Elderly  4S is also the first clinical trial to clearly demonstrate that cholesterol-lowering therapy reduces the risk of all-cause mortality (34%) and major coronary events (34%) in CHD patients >  65 years of age.  The observed RR reduction in both mortality categories, as well as for other secondary and tertiary CHD end points were as great as, or greater than those seen in younger patients.  Because mortality and CHD event rates increased with age, the absolute reductions in deaths and events were substantially greater for patients >  65 compared with those  65 compared with those < 65 years of age. Circulation. 1997;96:4211-4218

21. Conclusions  Cholesterol lowering with simvastatin produced similar reductions in relative risk for MCE in women compared with men and in elderly (>65 years of age) compared with younger patients.  There were too few female deaths to assess the effects on mortality in women.  Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause mortality and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients. Circulation. 1997;96:4211-4218