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A substantial evidence base supports a direct association between low-density lipoprotein cholesterol (LDL-C) levels and morbidity and mortality from cardiovascular disease (CVD).1 Meta-analyses of the many randomised controlled clinical trials (RCTs) suggest that the clinical impact is directly related to the magnitude of reduction and achieved levels of LDL-C.2 Together, these findings support a causal relationship leading to the mantra ‘Lower is Better’ with regard to LDL-C-lowering for CVD prevention. However, the vast majority of these RCTs were studies of statin therapy versus placebo or higher intensity versus standard doses of statins.
Ezetimibe inhibits cholesterol absorption by blocking Niemann-Pick C1-Like 1 (NPC1L1) protein on intestinal epithelial cells.3 The standard clinical dose of 10 mg/day consistently lowers LDL-C by 10–20% even in combination with statin.4 Its use in hypercholesterolaemia has been endorsed by a National Institute for Health and Care Excellence Health Technology Appraisal and is recommended in several national and international guidelines. However, these recommendations are based on modelling the impact of LDL-C reduction on clinical events in the absence of outcome studies. Recent negative RCTs with other lipid modifying therapies, including niacin, fibrates and cholesteryl ester transfer protein (CETP) inhibitors, question the received wisdom of extrapolating results from one drug class to another. The IMPROVE-IT study in acute coronary syndrome (ACS) patients is the only outcome trial directly evaluating ezetimibe in addition to statin. This will complete later this year and should report shortly thereafter. Ezetimibe is a safe, well-tolerated drug and has been extensively prescribed worldwide. Thus, considerable real world data are available to shed light on whether this alternative LDL-C management strategy might improve clinical outcomes.
To this end, Pauriah et al5 have conducted an interesting study investigating all-cause mortality in UK patients surviving their first acute myocardial infarction. They identified 9597 patients …
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