Scandinavian Simvastatin Survival Study

In an elegant paper, Gerdes et al. [59] examined whether the risk of death or a major coronary event in survivors of myocardial infarction (MI) was related to the apo E genotype and whether risk reduction brought about by simvastatin was different between genotypes. They analyzed 5.5 years of follow-up data of 966 Danish and Finish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study and found that MI survivors with the apo E4 allele have a nearly 2-fold increased risk of death, and that treatment with simvastatin abolished excess mortality. They concluded that the effect of apo E4 may involve mechanisms unrelated to serum lipoproteins because... 

Gerdes LU, Gerdes C, Kervinen K, Sa-volainen M, Klausen IC, Hansen PS, et al. The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction a substudy of the Scandinavian simvastatin survival study. Circulation 2000 101 1366-1371. 

For clinical studies demonstrating that statins are effective in the various populations mentioned, see Scandinavian Simvastatin Survival Study T. R. Pedersen A. G Olsson,... 

Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease ... 

TR Pedersen, J Kjekshus, K Berg, T Haghfelt, O Faergeman, G Thorgeirsson, K Pyorala, T Miettinen, AG Olsson, H Wedel, L Wilhelmsen. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease the Scandinavian Simvastatin Survival Study (4S). Lancet 344 1383-1389, 1994. 

In a subgroup of patients treated with simvastatin in the Scandinavian Simvastatin Survival Study, the RR of new claudication or worsening of preexisting claudication was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 1.3% points), as compared with patients randomly assigned to placebo (12). 

Pedersen TR, Kjekshus J, Pyorala K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1998 81 333-335. 

The purpose of altering plasma lipoprotein levels is to reduce the risk of coronary events. The results of outcome trials are available for lovastatin (Downs et al, 1998), simvastatin (Scandinavian Simvastatin Survival Study Group 1994), and pravastatin (Shepherd et al, 1995 Sacks et al, 1996 The Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group, 1998). Three of these trials, 4S, Cholesterol and Recurrent Events (CARE), and LIPID, studied patients with CHD, whereas the West of Scotland Coronary Revention Study Group and the Air Force Coronary Atherosclesosis Prevention Study (AFCAPS) evaluated the benefits of therapy in patients without known CHD. The main results of these trials are summarized in Tables la and lb. 

In the megatrials, the impact of inhibitors of HMG-CoA reductase on CHD appears to begin after approximately 1 year of therapy and to increase steadily thereafter as exemplified by 4S (Scandinavian Simvastatin Survival Study Group 1994). The claim by the WOS investigators (Shepherd et al., 1995) that pravastatin produced an earlier effect than... 

Scandinavian Simvastatin Survival Study Group 1994. b Shepherd et al. (1995). 

FU, follow-up P, interaction between placebo and statin therapy NR, not reported RR, relative risk Cl, confidence interval 4S, Scandinavian Simvastatin Survival Study REGRESS, Regression Growth Evaluation Statin Study CARE, Cholesterol and Recurrent Events CETP, Cholestery 1 ester transfer protein GP, glycoprotein CV, cardiovascular MI, myocardial infarction. 

Finally, a pharmacogenomic study of the Scandinavian Simvastatin Survival Study (4S) investigated the impact of the apolipopro-tein E4 allele with the prognosis and treatment response to either simvastatin or placebo (121). Among myocardial infarction survivors who received placebo and had at least one apolipoprotein E4 allele, the relative risk for all cause mortality was 1.9 (95% Cl, 1.1-3.1). The detrimental impact of the E4 allele was not evident among patients who received simvastatin (RR 0.33 95% Cl, 0.16-0.69). 

Scandinavian Simvastatin Survival Study AC AT acyl CoA cholesterol acyltransferase AFCAPS/TexCAPS Air Eorce/Texas Coronary Atherosclerosis... 

---