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• W2086348564 abstract "One unresolved issue of HPS1Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Summary Full Text Full Text PDF PubMed Scopus (7613) Google Scholar is whether there is a true and sustained linear relation between LDL cholesterol lowering and event reduction over a wide range of LDL cholesterol concentrations. The HPS investigators suggest that a threshold LDL cholesterol concentration does not exist, and call for aggressive LDL cholesterol lowering. Indeed, others have also suggested that lower is better by extrapolating data from the placebo and treated groups in other secondary prevention trials. Before HPS, interpretations of trial data, such as that represented in the figure by the dashed line, have been used to support the dogma that lower is better.2Kastelein JJP The future of best practice.Atherosclerosis. 1999; 143: S17-S21Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar Versions of the figure (minus the HPS data points) have been widely promulgated by proponents in lectures at international symposia. We suggest that, taken together with previous statin studies, HPS may not in fact support the lower is better concept. The overall event rates in the treated groups in HPS and 4S3Scandinavian Simvastatin Survival Study Group Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389Summary PubMed Scopus (11241) Google Scholar are similar, yet the lower absolute LDL cholesterol concentration in HPS did not translate into reduced events when compared with 4S (figure). This result cannot be explained by major baseline differences between the groups because the placebo groups in both trials had roughly the same major event rate. Additionally, the proportional reductions in risk did not seem to be associated with pretreatment LDL cholesterol concentrations in HPS.1Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Summary Full Text Full Text PDF PubMed Scopus (7613) Google Scholar If lower is better, the change in LDL cholesterol should have the highest effect in those with the highest baseline LDL cholesterol concentrations, and in those with the greatest LDL cholesterol reduction. The CARE study4Sacks FM Pfeffer MA Moye LA et al.for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.N Engl J Med. 1996; 335: 1001-1009Crossref PubMed Scopus (7182) Google Scholar also indicates that lower may not be better, and suggests a threshold LDL cholesterol concentration below which benefit is not apparent. Statin trials mainly show that the treatment with active medication results in clinical benefit. Mechanistic explanations of this finding, including that of cholesterol lowering, remain inferential. In aggregate, data from statin trials also support the existence of a set benefit, possibly drug-specific, that is largely dissociated from the degree to which LDL cholesterol is lowered. This set benefit in HPS amounted to about 25% reduction in event rate and is in keeping with other large secondary prevention studies. We await an analysis of HPS to examine the relation between LDL cholesterol decrease and risk reduction similar to that provided for the CARE4Sacks FM Pfeffer MA Moye LA et al.for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.N Engl J Med. 1996; 335: 1001-1009Crossref PubMed Scopus (7182) Google Scholar and WOSCOPS5West of Scotland Coronary Prevention Study Group Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS).Circulation. 1998; 97: 1440-1445Crossref PubMed Scopus (788) Google Scholar trials. Trials currently in progress directly address whether therapy should pursue the lowest achievable LDL cholesterol concentration. Until they report, it would seem prudent to treat patients with a statin in the categories for which benefit has been shown in HPS, even at LDL cholesterol concentrations of below 3·0 mmol/L, without necessarily forcing titration of LDL cholesterol to the lowest achievable level. C J Vaughan and B M Buckley have received funding for research and fees for consultancy and lecturing from all manufacturers of statin therapy. MRC/BHF Heart Protection StudyAuthors' reply Full-Text PDF" @default.
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• W2086348564 date "2002-11-01" @default.
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• W2086348564 title "MRC/BHF Heart Protection Study" @default.
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• W2086348564 doi "https://doi.org/10.1016/s0140-6736(02)11686-2" @default.
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