Several guidelines and expert recommendations have been published recently regarding the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) risk. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a drastic paradigm change in the treatment of cholesterol where treatment, based on level of cardiovascular risk, is based around using a fixed statin intensity therapy. This approach is endorsed by the American Diabetes Association. However, recommendations by the National Lipid Association (NLA) consist of the traditional approach of titrating therapy to achieve patient-specific lipoprotein targets. Despite the differences in overall approaches, the use of statin therapy as the cornerstone of treatment to reduce risk of cardiovascular events in at risk patients is a strong common theme. Clinicians should be aware of these differences, as they represent controversies with the overall treatment of ASCVD risk. Additional controversies related to the treatment of patients with ASCVD risk pertain to the role of nonstatin drugs and approaches to managing side effects. These topics are reviewed within this article and discuss implications for patient care.
GoASMozaffarianDRogerVL. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28–e292.
2.
CarrollMDKitBKLacherDA. Trends in lipids and lipoproteins in US adults, 1988-2010. JAMA. 2012;308(15):1545–1554.
3.
Chisholm-BurnsMAKim LeeJSpiveyCA. US pharmacists’ effect as team members on patient care: systematic review and meta-analyses. Med care. 2010;48(10):923–933.
4.
SandhoffBGNiesLKOlsonKL. Clinical pharmacy cardiac risk service for managing patients with coronary artery disease in a health maintenance organization. Am J Health Syst Pharm. 2007;64(1):77–84.
5.
SantschiVChioleroAParadisG. Pharmacist interventions to improve cardiovascular disease risk factors in diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care. 2012;35(12):2706–2717.
6.
SantschiVChioleroABurnandB. Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials. Arch Intern Med. 2011;171(16):1441–1453.
7.
Expert Panel on Detection, Evaluation Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497.
8.
GrundySMCleemanJIMerzCN. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–239.
9.
Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269(23):3015–3023.
10.
StoneNJRobinsonJGLichtensteinAH. 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(25 suppl 2):s1–s45.
11.
JacobsonTAItoMKMakiKC. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin Lipidol. 2014;8(5):473–488.
ShepherdJCobbeSMFordI. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301–1307.
14.
DownsJRClearfieldMWeisS. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–1622.
15.
ShepherdJBlauwGJMurphyMB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–1630.
16.
SeverPSDahlofBPoulterNR. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149–1158.
17.
ColhounHMBetteridgeDJDurringtonPN. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–696.
18.
NakamuraHArakawaKItakuraH. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368(9542):1155–1163.
19.
RidkerPMDanielsonEFonsecaFA. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207.
20.
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4 S). Lancet. 1994;344(8934):1383–1389.
21.
SacksFMPfefferMAMoyeLA. 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.
22.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):1349–1357.
23.
SchwartzGGOlssonAGEzekowitzMD. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285(13):1711–1718.
24.
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(9326):7–22.
25.
CannonCPBraunwaldEMcCabeCH. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–1504.
26.
de LemosJABlazingMAWiviottSD. 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(11):1307–1316.
27.
LaRosaJCGrundySMWatersDD. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–1435.
28.
PedersenTRFaergemanOKasteleinJJ. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437–2445.
29.
AmarencoPBogousslavskyJCallahanAIII. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–559.
30.
GoffDCJrLloyd-JonesDMBennettG. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):s49–s73.
31.
Expert Dyslipidemia Panel of the International Atherosclerosis Society Panel. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia--full report. J Clin Lipidol. 2014;8(1):29–60.
32.
American Diabetes Association. Cardiovascular disease and risk management. Diabetes Care. 2015;38 suppl: s49–s57.
33.
TonelliMWannerC, for the Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group M. Lipid Management in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2013 Clinical Practice Guideline. Ann Intern Med. 2014;160(3):182.
34.
BoekholdtSMHovinghGKMoraS. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–494.
35.
TaylorFWardKMooreTH. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011;19(1):CD004816.
36.
TaylorFHuffmanMDMacedoAF. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD004816.
37.
BrugtsJJYetginTHoeksSE. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376.
38.
TaylorFCHuffmanMEbrahimS. Statin therapy for primary prevention of cardiovascular disease. JAMA. 2013;310(22):2451–2452.
39.
MihaylovaBEmbersonJBlackwellL. 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.
40.
ChokshiNPMesserliFHSutinD. Appropriateness of statins in patients aged >/=80 years and comparison to other age groups. Am J Cardiol. 2012;110(10):1477–1481.
41.
LoweRNVande GriendJPSaseenJJ. Statins for the primary prevention of cardiovascular disease in the elderly. Consult Pharm. 2015;30(1):20–30.
42.
MuntnerPColantonioLDCushmanM. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA. 2014;311(14):1406–1415.
43.
KavousiMLeeningMJNanchenD. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA. 2014;311(14):1416–1423.
44.
GudzuneKAMonroeAKSharmaR. Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review. Ann Intern Med. 2014;160(7):468–476.
45.
JacobsonTA. NLA Task Force on Statin Safety--2014 update. J Clin Lipidol. 2014;8(3 suppl):s1–s4.
46.
The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984;251(3):351–364.
47.
CannerPLBergeKGWengerNK. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–1255.
48.
JunMFooteCLvJ. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–1884.
49.
StoneNJ. The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors. Curr Cardiol Rep. 2000;2(5):445–451.
50.
CannonCPBlazingMAGiulianoRP. Ezetimibe added to Statin Therapy after acute coronary syndromes. NEJM. 2015;372(25):2387–2397.
51.
BodenWEProbstfieldJLAndersonT. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–2267.
52.
GinsbergHNElamMBLovatoLC. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–1574.
53.
GuytonJRSleeAEAndersonT. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013;62(17):1580–1584.
54.
McKenneyJMDavidsonMHJacobsonTA. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8a):89c–94c.
55.
U.S. Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Updated 7/3/12. Web site. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed November 8, 2015.
Rojas-FernandezCHGoldsteinLBLeveyAI. An assessment by the Statin Cognitive Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 suppl):s5–s16.
58.
RichardsonKSchoenMFrenchB. Statins and cognitive function: a systematic review. Ann Intern Med. 2013;159(10):688–697.
59.
OttBRDaielloLADahabrehIJ. Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Gen Intern Med. 2015;30(3):348–358.
60.
SattarNPreissDMurrayHM. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–742.
61.
PreissDSeshasaiSRWelshP. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–2564.
62.
WatersDDHoJEBoekholdtSM. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol. 2013;61(2):148–152.
63.
RidkerPMPradhanAMacFadyenJG. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565–571.
64.
MakiKCRidkerPMBrownWV. An assessment by the Statin Diabetes Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 suppl):s17–s29.
65.
BaigentCKeechAKearneyPM. 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(9493):1267–1278.
66.
EckelRHJakicicJMArdJD. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):s76–s99.
67.
RosensonRSBakerSKJacobsonTA. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 suppl):s58–s71.
68.
ParkerBACapizziJAGrimaldiAS. Effect of statins on skeletal muscle function. Circulation. 2013;127(1):96–103.
69.
ParkerBAAugeriALCapizziJA. Effect of statins on creatine kinase levels before and after a marathon run. Am J Cardiol. 2012;109(2):282–287.
70.
GuptaAThompsonPD. The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis. 2011;215(1):23–29.
71.
MarcoffLThompsonPD. The role of coenzyme Q10 in statin-associated myopathy: a systematic review. J Am Coll Cardiol. 2007;49(23):2231–2237.
72.
ParkerBAGregorySMLorsonL. A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design. J Clin Lipidol. 2013;7(3):187–193.
73.
BruckertEHayemGDejagerS. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther. 2005;19(6):403–414.
74.
GangaHVSlimHBThompsonPD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J. 2014;168(1):6–15.
