Hyperlipidemia: Drugs for Cardiovascular Risk Reduction in Adults
Am Fam Physician. 2017 Jan 15;95(2):78-87.
Related editorial: The Cholesterol Dilemma: Treating the Risk or Treating to LDL-C Goal?
Related U.S. Preventive Services Task Force recommendation statement: Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement
Author disclosure: No relevant financial affiliations.
Guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) and the U.K. National Institute for Health and Care Excellence (NICE) indicate that lipid-lowering drugs have benefit for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) events. The evidence is strongest for statins. ACC/AHA, NICE, and U.S. Preventive Services Task Force (USPSTF) guidelines recommend statin therapy based on patients' risk of an ASCVD event, rather than treating to specific lipid levels. For patients with no previous ASCVD event, risk calculators should be used to determine the 10-year risk of ASCVD. The ACC/AHA guideline recommends starting moderate- to high-intensity statins if the risk is 7.5% or greater, whereas the NICE and USPSTF guidelines recommend statins if the risk is 10% or greater. Patients with known ASCVD should receive high-intensity statins unless they fall into special categories (e.g., older age) or do not tolerate high-intensity statins, in which case moderate-intensity statins are appropriate. Liver transaminase levels should be checked before starting statins; guidelines vary on if and when to recheck them in the absence of symptoms. Lipid levels should be rechecked one to three months after starting statins, although guidelines differ on subsequent checks. Other lipid-lowering drugs (e.g., bile acid sequestrants, ezetimibe) can be considered if patients do not tolerate statins. Niacin should not be used. Some evidence supports adding ezetimibe to statin therapy in patients with acute coronary syndrome or chronic kidney disease. The role of proprotein convertase subtilisin/kexin type 9 inhibitors is unclear, but initial studies suggest a decrease in the rate of acute ASCVD events in patients with hypercholesterolemia.
The American College of Cardiology (ACC) and the American Heart Association (AHA) jointly issued a new guideline in 2013 on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.1 This guideline presented significant changes to previous recommendations on the management of hyperlipidemia for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), which includes acute coronary syndrome, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, and peripheral arterial disease presumed to be of atherosclerotic origin.
WHAT IS NEW ON THIS TOPIC: HYPERLIPIDEMIA
A Cochrane review found that for every 1,000 persons treated with a statin for five years, 18 avoid myocardial infarction, angina, or stroke (number needed to treat = 56). This review focused on studies that included fewer than 10% of participants with known cardiovascular disease.
A meta-analysis of 13 trials involving more than 90,000 patients found that statin use increases the overall absolute risk of developing diabetes mellitus by 0.39% (number needed to harm = 255) over four years.
In early 2016, the U.S. Food and Drug Administration withdrew approvals for extended-release niacin and delayed-release fenofibric acid (fibrate) in combination with statins based on lack of cardiovascular benefit.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
|Clinical recommendation||Evidence rating||References||Comments|
Patients with a high risk of ASCVD (a 10-year risk of at least 7.5% or 10%, depending on the guideline) should receive statin therapy for primary prevention.
Inconsistent results from meta-analyses regarding benefit in low-risk patients
Statin therapy should be prescribed for secondary prevention in patients with known ASCVD, unless contraindicated.
Recommendation from consensus guidelines and meta-analyses
Niacin, fibrates, and omega-3 fatty acids should not be routinely prescribed for primary or secondary prevention of ASCVD. Although these agents lower cholesterol levels, they do not affect patient-oriented outcomes.
Consistent results in meta-analyses and systematic review
A moderate-intensity statin plus ezetimibe should be considered as an alternative in patients with acute coronary syndrome who do not tolerate high-intensity statin therapy.
One randomized controlled trial with high discontinuation rates
ASCVD = atherosclerotic cardiovascular disease.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.
REFERENCESshow all references
1. 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 [published corrections appear in J Am Coll Cardiol. 2015;66(24):2812, and J Am Coll Cardiol. 2014;63(25 pt B):3024–3025]. J Am Coll Cardiol. 2014;63(25 pt B):2889–2934....
2. National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. NICE clinical guideline CG181. July 2014. http://www.nice.org.uk/guidance/cg181. Accessed October 30, 2015.
3. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA. 2016;316(19):1997–2007.
4. Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ. 2008;336(7659):1475–1482.
5. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC Expert Consensus Decision Pathyway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016;68(1):92–125.
6. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet. 2013;382(9907):1762–1765.
7. Pursnani A, Massaro JM, D'Agostino RB Sr, O'Donnell CJ, Hoffmann U. Guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. JAMA. 2015;314(2):134–141.
8. Johnson KM, Dowe DA. Accuracy of statin assignment using the 2013 AHA/ACC Cholesterol Guideline versus the 2001 NCEP ATP III guideline: correlation with atherosclerotic plaque imaging. J Am Coll Cardiol. 2014;64(9):910–919.
9. Grundy SM, Cleeman JI, Merz CN, et al.; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines [published correction appears in Circulation. 2004;110(6):763]. Circulation. 2004;110(2):227–239.
10. Ioannidis JP. More than a billion people taking statins? Potential implications of the new cardiovascular guidelines. JAMA. 2014;311(5):463–464.
11. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816.
12. Sattar N, Preiss D, Murray HM, et al. Statins and the incident risk of diabetes: a collaborative meta-analyis of randomised statin trials. Lancet. 2010;375(9716):735–742.
13. American Academy of Family Physicians. Clinical practice guideline. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. June 2014. http://www.aafp.org/patient-care/clinical-recommendations/all/cholesterol.html. Accessed March 3, 2016.
14. Kelly RB. Diet and exercise in the management of hyperlipidemia. Am Fam Physician. 2010;81(9):1097–1102.
15. DynaMed. Statins for primary and secondary prevention of cardiovascular disease. June 8, 2016. https://www.dynamed.com/topics/dmp~AN~T115052 [login required]. Accessed October 19, 2016.
16. Pandya A, Sy S, Cho S, Weinstein MC, Gaziano TA. Cost-effectiveness of 10-year risk thresholds for initiation of statin therapy for primary prevention of cardiovascular disease [published correction appears in JAMA. 2015;314(15):1647]. JAMA. 2015;314(2):142–150.
17. Mihaylova B, Emberson J, Blackwell L, et al.; Cholesterol Treatment Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–590.
18. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? [published correction appears in BMJ. 2014;348:g3329]. BMJ. 2013;347:f6123.
19. Yusuf S, Bosch J, Dagenais BG, et al.; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–2031.
20. Sando KR, Knight M. Nonstatin therapies for management of dyslipidemia: a review. Clin Ther. 2015;37(10):2153–2179.
21. Landray MJ, Haynes R, Hopewell JC, et al.; HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–212.
22. U.S. Food and Drug Administration. Withdrawal of approval of indications related to the coadministration with statins in applications for niacin extended-release tablets and fenofibric acid delayed-release capsules. Federal Register. April 18, 2016. https://www.federalregister.gov/articles/2016/04/18/2016-08887/abbvie-inc-et-al-withdrawal-of-approval-of-indications-related-to-the-coadministration-with-statins. Accessed October 17, 2016.
23. 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(1):40–51.
24. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–1009.
25. Fulcher J, O'Connell R, Voysey M, et al.; Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397–1405.
26. Gutierrez J, Ramirez G, Rundek T, Sacco RL. Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis. Arch Intern Med. 2012;172(12):909–919.
27. 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(11):1409–1415.
28. Wilt TJ, Bloomfield HE, MacDonald R, et al. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med. 2004;164(13):1427–1436.
29. Zhou Z, Rahme E, Pilote L. Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. Am Heart J. 2006;151(2):273–281.
30. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Circulation. 2002;106(8):1024–1028.
31. Cannon CP, Blazing MA, Giugliano RP, et al.; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
32. Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and mono-therapy for dyslipidemia. Ann Intern Med. 2009;151(9):622–630.
33. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165(7):725–730.
34. Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–1884.
35. Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ. 2014;349:g4379.
36. Boden WE, Probstfield JL, Anderson T, et al.; AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy [published correction appears in N Engl J Med. 2012; 367(2)189]. N Engl J Med. 2011;365(24):2255–2267.
37. Kwak SM, Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172(9):686–694.
38. Yokoyama M, Origasa H, Matsuzaki M, et al.; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis [published correction appears in Lancet. 2007;370(9583):220]. Lancet. 2007;369(9567):1090–1098.
39. Duggal JK, Singh M, Attri N, et al. Effect of niacin therapy on cardiovascular outcomes in patients with coronary artery disease. J Cardiovasc Pharmacol Ther. 2010;15(2):158–166.
40. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002;105(16):1897–1903.
41. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43(8):2149–2156.
42. Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev. 2007;(4):CD000123.
43. Antoniou GA, Fisher RK, Georgiadis GS, Antoniou SA, Torella F. Statin therapy in lower limb peripheral arterial disease: systematic review and meta-analysis. Vascul Pharmacol. 2014;63(2):79–87.
44. Twine CP, Williams IM. Systematic review and meta-analysis of the effects of statin therapy on abdominal aortic aneurysms. Br J Surg. 2011;98(3):346–353.
45. Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis [published correction appears in J Am Coll Cardiol. 2014;63(11):1122]. J Am Coll Cardiol. 2013;62(22):2090–2099.
46. Afilalo J, Duque G, Steele R, Jukema JW, de Craen AJ, Eisenberg MJ. Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J Am Coll Cardiol. 2008;51(1):37–45.
47. Galindo-Ocaña J, Bernabeu-Wittel M, Formiga F, et al.; PROFUND Project researchers. Effects of renin-angiotensin blockers/inhibitors and statins on mortality and functional impairment in polypathological patients. Eur J Intern Med. 2012;23(2):179–184.
48. Palmer SC, Navaneethan SD, Craig JC, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2014;(5):CD007784.
49. Palmer SC, Navaneethan SD, Craig JC, et al. HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev. 2013;(9):CD004289.
50. Baigent C, Landray MJ, Reith C, et al.; SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–2192.
51. Last AR, Ference JD, Falleroni J. Pharmacologic treatment of hyperlipidemia [published correction appears in Am Fam Physician. 2012;86(10): 889]. Am Fam Physician. 2011;84(5):551–558.
52. Safeer RS, Lacivita CL. Choosing drug therapy for patients with hyperlipidemia. Am Fam Physician. 2000;61(11):3371–3382.
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