Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease
- David M Rind, MD
David M Rind, MD
- Section Editor — General Medicine
- Chief Medical Officer
- Institute for Clinical and Economic Review
- Assistant Professor of Medicine, Part-time
- Harvard Medical School
- Rodney A Hayward, MD
Rodney A Hayward, MD
- Professor of Medicine and Public Health
- University of Michigan
Patients with known cardiovascular disease (CVD) are at high risk for CV events. Treatment in such patients, as well as in other patients known to have a similar risk of CV events, is discussed as secondary prevention. In secondary prevention, statins have been shown in multiple large trials to reduce CV events and to reduce all-cause mortality. Trials of other lipid-lowering agents have generally only shown reductions in CV events.
Trials of statins, and other medications used in combination with statins, have provided additional information that is related to the appropriate serum low-density lipoprotein cholesterol (LDL-C) target in patients being treated for secondary prevention. However, the results of these trials are open to various interpretations and the ideal target LDL-C level has not been completely defined.
This topic will review the evidence for LDL-C goals in patients treated with statins for secondary prevention of CHD, as well as the evidence for using agents other than statins in patients who are unable to tolerate statins or who do not achieve LDL-C goals with statins alone. The general approach to lipid lowering therapy for secondary prevention and in patients with an acute coronary syndrome, as well as an overview of the treatment of hypercholesterolemia, are discussed separately. (See "Prevention of cardiovascular disease events in those with established disease or at high risk", section on 'Dyslipidemia' and "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention".)
Treatment to prevent cardiovascular events in patients with known coronary heart disease (CHD; including myocardial infarction, angina, and prior coronary revascularization), other cardiovascular disease (CVD; including stroke, transient ischemic attack, and peripheral arterial disease), or combinations of risk factors that result in a 10-year risk of CVD events of more than 20 percent (table 1), is discussed as secondary prevention. (See "Treatment of lipids (including hypercholesterolemia) in secondary prevention", section on 'Identification of patients at risk'.)
Moderate-intensity statin therapy includes daily treatment with:
Subscribers log in hereTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:Literature review current through: May 2017. | This topic last updated: Apr 19, 2017.References
- Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:227.
- Stone NJ, Robinson JG, 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. Circulation 2014; 129:S1.
- Mills EJ, O'Regan C, Eyawo O, et al. Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients. Eur Heart J 2011; 32:1409.
- Mills EJ. University of Ottawa. Personal communication 2011.
- Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011; 365:2078.
- Heart 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.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372:2387.
- Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495.
- de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292:1307.
- 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.
- Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005; 294:2437.
- Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage J, Bowman L, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010; 376:1658.
- Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation 2007; 115:700.
- Wenger NK, Lewis SJ, Herrington DM, et al. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med 2007; 147:1.
- Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med 2015; 163:40.
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376:1713.
- Jarcho JA, Keaney JF Jr. Proof That Lower Is Better--LDL Cholesterol and IMPROVE-IT. N Engl J Med 2015; 372:2448.
- Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376:1670.
- Snow V, Aronson MD, Hornbake ER, et al. Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2004; 140:644.
- Hayward RA, Hofer TP, Vijan S. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med 2006; 145:520.
- Hsia J, MacFadyen JG, Monyak J, Ridker PM. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol <50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol 2011; 57:1666.
- Everett BM, Mora S, Glynn RJ, et al. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (<30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER). Am J Cardiol 2014; 114:1682.
- Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res 2009; 50 Suppl:S172.
- Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372:1489.
- Rosenson R, Lloyd-Jones D, Working group from the Adult Treatment Panel III of the National Cholesterol Educational Program. Critical appraisal of revised cholesterol guidelines for the very high-risk patient. Expert Rev Cardiovasc Ther 2005; 3:173.
- Dale KM, White CM, Henyan NN, et al. Impact of statin dosing intensity on transaminase and creatine kinase. Am J Med 2007; 120:706.
- SEARCH Collaborative Group, Link E, Parish S, et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med 2008; 359:789.
- Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005; 165:725.
- Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366:1849.
- ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362:1563.
- Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341:410.
- Saha SA, Kizhakepunnur LG, Bahekar A, Arora RR. The role of fibrates in the prevention of cardiovascular disease--a pooled meta-analysis of long-term randomized placebo-controlled clinical trials. Am Heart J 2007; 154:943.
- Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357:2109.
- AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365:2255.
- HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371:203.
- Anderson TJ, Boden WE, Desvigne-Nickens P, et al. Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med 2014; 371:288.
- Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med 2009; 151:622.
- INTENSIVE THERAPY
- Baseline LDL-C
- Differential effects on events and mortality
- - Acute coronary syndrome
- - Stable CHD
- - Pleiotropic effects
- Medication choice versus goal LDL
- - Medication choice strategy
- - Minimum LDL
- Putting the evidence together
- USE OF MEDICATIONS OTHER THAN STATINS
- RECOMMENDATIONS OF OTHERS
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Acute coronary syndrome
- Stable CVD