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Can the Reduction in Percent LDL Cholesterol or Attained LDL Cholesterol Levels or Both Add Incremental Prognostic Value?
EDITORIAL
Can the Reduction in Percent LDL Cholesterol or Attained LDL Cholesterol Levels or Both Add Incremental Prognostic Value? 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.1-4 The decrease in LDL-C levels leads to a significant reduction in the risk of atherosclerotic cardiovascular disease.5 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.3-5 In a recent meta-analysis involving 38,153 patients, Boekholdt et al6 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.6 In a meta-regression analysis of secondary prevention trials, LaRosa et al7 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 al8 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.8 Boekholdt et al6 performed a meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were Funding: None. Conflict of Interest: None. Authorship: The author had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Leonardo Roever, MHS, Department of Clinical Research, Av. Pará, 1720 - Bairro, Umuarama, Uberlândia, MG - CEP 38400-902, Brazil. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2015.11.002
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.6 In this issue of The American Journal of Medicine, Bangalore et al9 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.9 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%. Leonardo Roever, MHS Department of Clinical Research Federal University of Uberlândia Uberlândia, Brazil
References 1. Roy S. Atherosclerotic cardiovascular disease risk and evidencebased management of cholesterol. N Am J Med Sci. 2014;6: 191-198. 2. Gotto AM. Evolving concepts of dyslipidemia, atherosclerosis, and cardiovascular disease. J Am Coll Cardiol. 2005;46:1219-1224. 3. Kosmas CE, Frishman WH. New and emerging LDL cholesterol-lowering drugs. Am J Ther. 2015;22:234-241.
2 4. Adhyaru BB, Jacobson TA. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk. Cardiol Clin. 2015;33:181-196. 5. Stone NJ, Robinson J, Lichtenstein AH, 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;63:2889-2934. 6. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a metaanalysis of statin trials. J Am Coll Cardiol. 2014;64:485-494.
The American Journal of Medicine, Vol -, No -,
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2015
7. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-1435. 8. Baigent C, Keech A, Kearney PM, 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: 1267-1278. 9. Bangalore S, Fayyad R, Kastelein JJ, 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.
Can the Reduction in Percent LDL Cholesterol or Attained LDL Cholesterol Levels or Both Add Incremental Prognostic Value? 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.1-4 The decrease in LDL-C levels leads to a significant reduction in the risk of atherosclerotic cardiovascular disease.5 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.3-5 In a recent meta-analysis involving 38,153 patients, Boekholdt et al6 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.6 In a meta-regression analysis of secondary prevention trials, LaRosa et al7 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 al8 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.8 Boekholdt et al6 performed a meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were Funding: None. Conflict of Interest: None. Authorship: The author had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Leonardo Roever, MHS, Department of Clinical Research, Av. Pará, 1720 - Bairro, Umuarama, Uberlândia, MG - CEP 38400-902, Brazil. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2015.11.002
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.6 In this issue of The American Journal of Medicine, Bangalore et al9 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.9 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%. Leonardo Roever, MHS Department of Clinical Research Federal University of Uberlândia Uberlândia, Brazil
References 1. Roy S. Atherosclerotic cardiovascular disease risk and evidencebased management of cholesterol. N Am J Med Sci. 2014;6: 191-198. 2. Gotto AM. Evolving concepts of dyslipidemia, atherosclerosis, and cardiovascular disease. J Am Coll Cardiol. 2005;46:1219-1224. 3. Kosmas CE, Frishman WH. New and emerging LDL cholesterol-lowering drugs. Am J Ther. 2015;22:234-241.
2 4. Adhyaru BB, Jacobson TA. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk. Cardiol Clin. 2015;33:181-196. 5. Stone NJ, Robinson J, Lichtenstein AH, 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;63:2889-2934. 6. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a metaanalysis of statin trials. J Am Coll Cardiol. 2014;64:485-494.
The American Journal of Medicine, Vol -, No -,
-
2015
7. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425-1435. 8. Baigent C, Keech A, Kearney PM, 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: 1267-1278. 9. Bangalore S, Fayyad R, Kastelein JJ, 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.