Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists' Collaboration meta-analysis for low-density lipoprotein Lowering
ABSTRACT Researchers from the Cholesterol Treatment Trialists' (CTT) Collaboration have argued for maximal lowering of low-density lipoprotein cholesterol (LDL-C) by the use of pharmacologic agents, with the strongest evidence coming from the five comparison statin studies in their second meta-analysis. The CTT meta-analysis has many strengths but also a number of limitations, which have not been discussed and which, given the clinical implications, require consideration. Among these are: (1) the impact and validity of including revascularizations within a composite primary end point; (2) the inclusion of the A-Z study, whose design does not allow for valid comparisons of two statin regimens; (3) the fact that baseline LDL-C levels in the comparison studies were not low enough to test whether statin therapy reduces risk significantly in groups with an initial low LDL-C; and, most important, (4) authors of the five studies compared doses at the extremes of statin regimens. However, the clinical choice is not between the lowest and the greatest dose of a statin statin regimens, for example, between 10 and 80 mg atorvastatin, but, more realistically, between intermediate and high dose, that is, between 40 and 80 mg atorvastatin. On the basis of the CTT meta-analysis, we calculate that any potential gain from increasing the dose from 40 to 80 mg atorvastatin would be very small, at best a further 2% further reduction in clinical events. The increase in dose, unfortunately, would likely be associated with increased side effects and decreased compliance. Accordingly, whether net benefit would be demonstrable cannot be assumed. It follows that definitive evidence supporting maximal lowering of LDL-C or maximal dose of statins is still lacking and guidelines, if they are to be evidence-based, should acknowledge this uncertainty.
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ABSTRACT: CHD morbidity and mortality rates have more than halved since their peak in the 1960s and 1970s. This trend is a result of many factors; however, primary prevention provides the bulk of this benefit. Despite this tremendous progress, cardiovascular disease remains the major cause of death and this trend is projected to persist given the continuous growth in those aged 65 years or greater. Although statin therapy has been a main contributor to a primary prevention strategy, there is still controversy about exposing a large healthy population to long-term statin therapy. Advocates contend the mortality benefits from an aggressive statin approach would remove heart disease from its perch as the greatest killer of Americans and stroke mortality would drop from third to fifth place. Those advocating a much more conservative approach contend the data are not available to expose a healthy population to lifelong statin therapy given limited data on mortality, potential adverse events, and considerable costs. Given these opposing views, this summary of the evolution of statin therapy for the primary prevention of cardiovascular disease will review the major factors fueling this debate.Current Atherosclerosis Reports 02/2013; 15(2):298. DOI:10.1007/s11883-012-0298-0 · 3.06 Impact Factor