Can the Reduction in Percent LDL Cholesterol or Attained LDL Cholesterol Levels or Both Add Incremental Prognostic Value?

SEE RELATED ARTICLE p. 384 SEE RELATED ARTICLE p. 384 The role of low-density lipoprotein cholesterol (LDL-C) in the pathophysiology of atherosclerotic cardiovascular disease, which may present as coronary heart disease, stroke, and peripheral arterial disease, has been well documented in several studies.1Roy S. Atherosclerotic cardiovascular disease risk and evidence-based management of cholesterol.N Am J Med Sci. 2014; 6: 191-198Crossref PubMed Scopus (21) Google Scholar, 2Gotto A.M. Evolving concepts of dyslipidemia, atherosclerosis, and cardiovascular disease.J Am Coll Cardiol. 2005; 46: 1219-1224Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 3Kosmas C.E. Frishman W.H. New and emerging LDL cholesterol-lowering drugs.Am J Ther. 2015; 22: 234-241Crossref PubMed Scopus (13) Google Scholar, 4Adhyaru B.B. Jacobson T.A. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk.Cardiol Clin. 2015; 33: 181-196Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar The decrease in LDL-C levels leads to a significant reduction in the risk of atherosclerotic cardiovascular disease.5Stone N.J. Robinson J. Lichtenstein A.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014; 63: 2889-2934Abstract Full Text Full Text PDF PubMed Scopus (3312) Google Scholar Statins have become the first line in primary and secondary prevention of atherosclerotic cardiovascular disease because of their level of clinical benefit. Nevertheless, there are individuals at risk of atherosclerotic cardiovascular disease who fail to achieve treatment goals of LDL-C despite the use of maximal doses of statins.3Kosmas C.E. Frishman W.H. New and emerging LDL cholesterol-lowering drugs.Am J Ther. 2015; 22: 234-241Crossref PubMed Scopus (13) Google Scholar, 4Adhyaru B.B. Jacobson T.A. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk.Cardiol Clin. 2015; 33: 181-196Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 5Stone N.J. Robinson J. Lichtenstein A.H. et al.2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014; 63: 2889-2934Abstract Full Text Full Text PDF PubMed Scopus (3312) Google Scholar In a recent meta-analysis involving 38,153 patients, Boekholdt et al6Boekholdt S.M. Hovingh G.K. Mora S. et al.Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.J Am Coll Cardiol. 2014; 64: 485-494Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar showed that compared with patients who achieved an LDL-C level >175 mg/dL, those who reached very low levels (<50 mg/dL) had a significant decrease in major cardiovascular events.6Boekholdt S.M. Hovingh G.K. Mora S. et al.Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.J Am Coll Cardiol. 2014; 64: 485-494Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar In a meta-regression analysis of secondary prevention trials, LaRosa et al7LaRosa J.C. Grundy S.M. Waters D.D. et al.Intensive lipid lowering with atorvastatin in patients with stable coronary disease.N Engl J Med. 2005; 352: 1425-1435Crossref PubMed Scopus (3015) Google Scholar showed a significant reduction in cardiovascular events down to an LDL-C of 50 to 70 mg/dL. In a prospective meta-analysis of data from 90,056 individuals in 14 randomized trials of statins, Baigent et al8Baigent C. Keech A. Kearney P.M. et al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.Lancet. 2005; 366: 1267-1278Abstract Full Text Full Text PDF PubMed Scopus (5760) Google Scholar showed that for each 1.0 mmol/L reduction in LDL-C, there was a 12% proportional reduction in all-cause mortality and a 19% reduction in coronary mortality. There were corresponding reductions in myocardial infarction or coronary death and the need for coronary revascularization in fatal or nonfatal stroke.8Baigent C. Keech A. Kearney P.M. et al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.Lancet. 2005; 366: 1267-1278Abstract Full Text Full Text PDF PubMed Scopus (5760) Google Scholar Boekholdt et al6Boekholdt S.M. Hovingh G.K. Mora S. et al.Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.J Am Coll Cardiol. 2014; 64: 485-494Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar performed a meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were determined at baseline and 1-year follow-up. Among 38,153 patients allocated to statin therapy, 6286 major cardiovascular events occurred in 5387 study participants. More than 40% of trial participants did not reach an LDL-C target <70 mg/dL. The authors concluded that patients who achieve very low LDL-C levels have a lower risk of major cardiovascular events.6Boekholdt S.M. Hovingh G.K. Mora S. et al.Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.J Am Coll Cardiol. 2014; 64: 485-494Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar In this issue of The American Journal of Medicine, Bangalore et al9Bangalore S. Fayyad R. Kastelein J.J. et al.2013 cholesterol guidelines revisited: percent low-density lipoprotein cholesterol reduction or attained low-density lipoprotein cholesterol level or both for prognosis?.Am J Med. 2015; Google Scholar describe the implications of percent LDL-C reduction adding incremental prognostic value over both statin dose and attained LDL-C levels. This study combined individual patient-level data from 3 trials with different inclusion and exclusion criteria, but the patients included in the study were those with established atherosclerotic cardiovascular disease. Among patients who attained an LDL-C level ≤70 mg/dL, those with percent LDL-C reduction <50% had a significantly higher risk of primary outcome and stroke and a numerically higher risk of death when compared with the group with percent LDL-C reduction of ≥50%. The results of this study suggest that even patients with percent LDL-C reduction <50% from baseline had a considerable increase in the risk of cardiovascular events.9Bangalore S. Fayyad R. Kastelein J.J. et al.2013 cholesterol guidelines revisited: percent low-density lipoprotein cholesterol reduction or attained low-density lipoprotein cholesterol level or both for prognosis?.Am J Med. 2015; Google Scholar Clearly, additional trials need to be performed. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who fail to achieve percent LDL-C reduction <50%. 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?The American Journal of MedicineVol. 129Issue 4PreviewThe 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether percent low-density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known. Full-Text PDF