Volume 376, Issue 9753, Pages (November 2010)

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Volume 376, Issue 9753, Pages 1658-1669 (November 2010) Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial  Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group  The Lancet  Volume 376, Issue 9753, Pages 1658-1669 (November 2010) DOI: 10.1016/S0140-6736(10)60310-8 Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 1 Trial profile Numbers lost to follow-up relate to those without information to the end of the scheduled treatment period for mortality (as well as morbidity) and for morbidity alone. The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 2 Effects of simvastatin dose allocation on first major vascular event Analyses are of the numbers of participants having a first event of each type during follow-up (with non-fatal and fatal events considered separately), so there is some non-additivity between different types of event. Risk ratios are plotted comparing outcomes in participants allocated 80 mg simvastatin with those in participants allocated 20 mg simvastatin, along with 95% CIs. The dashed vertical line shows the overall risk ratio. MI=myocardial infarction. CHD=coronary heart disease. The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 3 Effects of simvastatin dose allocation on first major vascular event by year of follow-up Risk ratios are plotted comparing outcomes in participants allocated 80 mg simvastatin with those in participants allocated 20 mg simvastatin, along with 95% CIs. The dashed vertical line shows the overall risk ratio. Analyses are of numbers of participants having a first event during each year of follow-up and of those still at risk of a first event at the start of each year. The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 4 Effects of simvastatin dose allocation on first major vascular event in different categories of participant Risk ratios are plotted comparing outcomes in participants allocated 80 mg simvastatin with those in participants allocated 20 mg simvastatin, along with 95% CIs. The dashed vertical line shows the overall risk ratio. p values of χ2 tests are given for heterogeneity between RRs within dichotomous categories and for trend within other categories (except for previous disease categories since there is some overlap between them). Lipid categories relate to measured values at the randomisation visit after all participants had been taking 20 mg simvastatin daily for 2 months during the run-in. MI=myocardial infarction. CHD=coronary heart disease. GFR (MDRD)=glomerular filtration rate estimated with modification of diet in renal disease equation. The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 5 Effects of simvastatin dose allocation on cause-specific mortality Risk ratios are plotted comparing outcomes in participants allocated 80 mg simvastatin with those in participants allocated 20 mg simvastatin, along with 95% CIs. The dashed vertical line shows the overall risk ratio. MI=myocardial infarction. CHD=coronary heart disease. The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 6 Effect of simvastatin dose allocation on site-specific cancer incidence Risk ratios are plotted comparing outcomes in participants allocated 80 mg simvastatin with those in participants allocated 20 mg simvastatin, along with 95% CIs. The dashed vertical line shows the overall risk ratio. Analyses are of the numbers of participants developing cancer at each site (excluding recurrences or new cancers at the same site), so there is some non-additivity between cancers at different sites. Connective tissue includes breast, melanoma, skin, and other connective tissue cancers, but not non-melanoma skin cancer (which was prospectively to be considered separately). The Lancet 2010 376, 1658-1669DOI: (10.1016/S0140-6736(10)60310-8) Copyright © 2010 Elsevier Ltd Terms and Conditions