Cholesterol and recurrent events trial

Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996 335(14) 1001-9. 

Sacks, F.M., Moye, L.A., Davis, B.R., Cole, T.G., Rouleau, J.L., Nash, D.T., Pfeffer, M.A., Braunwald, E. 1998. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the cholesterol and recurrent events trial. Circulation. 97, 1446-1452. 

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. 

The ability of statins to lower hsCRP was first described for pravastatin using data accumulated in the Cholesterol and Recurrent Events (CARE) trial. These data were initially highly controversial because they suggested that statins have both hpid-lowering and antiinflammatory effects. However, confirmatory work rapidly showed the effect of statins on hsCRP to be a consistent and important class effect. Studies of atorvastatin, cerivastatin, lovastatin, pravastatin, and simvastatin have shown that, on average, median hsCRP concentrations decline 15% to 25% as early as 6 weeks after initiation of therapy. Importantly the magnitude of LDL cholesterol reduction caused by statin therapy is minimally correlated with the magnitude of hsCRP reduction. ... 

The Cholesterol and Recurrent Events (CARE) trial enrolled patients with a history of myocardial infarction and hypercholesterol-... 

Goldberg RB, Mellies MJ, Sacks EM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels Subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation 1998 98 2513-2519. 

With the advent of the statin class of drugs, lowering of low density lipoprotein (LDL) cholesterol to a meaningful degree became clinically achievable in most patients with vascular disease. There have been three large trials of statins in secondary prevention of MI (61) the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, the Cholesterol and Recurrent Events (CARE) study, and the Scandinavian... 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

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