Course:PHAR451/Lipid Management

Updated October 2016

Instructor

Dr. Peter Loewen, B.Sc.(Pharm), ACPR, Pharm.D., FCSHP | 604-827-1814

Objectives

After the session, and with reflection and study, students should be able to

1. Describe the differences in lipid-lowering and CV event reduction effects of different classes of antihyperlipidemic drugs
2. Estimate in quantitative terms the efficacy and toxicity of statin therapy in individual patient situations
3. Design and monitor a lipid-lowering drug therapy regimen based on individual patient factors

Preparation for the session

Read the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult

Review the posted SLIDES for the session in Connect.

In EVERY patient with CV disease or at risk for CV disease...

Think about

What is this patient’s level of CV risk?

Is drug therapy indicated?

If so, how would I explain the expected benefits and risks of drug (e.g., statin) therapy to them?

Definitions

CVD = coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, heart failure

CHD = coronary death, myocardial infarction, coronary insufficiency, angina

CAD = CHD

TChol = LDL+HDL+TG/5

mg/dL --> mmol/L CONVERSION FACTOR: 38.6

Summary of Statin Efficacy

Loewen's Little Black Book

Common Misconceptions and Sticking Points

• Do statins reduce OVERALL (total) mortality in primary prevention? | Probably, but there's some conflicting evidence. Brugts et al. BMJ 2009;338:b2376 vs. Ray KK Arch Intern Med. 2010;170(12):1024-1031 vs. Tonelli M. CMAJ 2011. DOI:10.1503 /cmaj.101280
• Do statins cause diabetes? | Maybe, but their benefits far outweigh this risk, and they're a first-line therapy in patients who get diabetes. Rajpathak SN, et al. Diabetes Care 2009;32 1924-1929 | JUPITER N Engl J Med 2008;359:2195-207 | Sattar N, et al. Lancet 2010;375:735-42
• Are statins useful for primary prevention in women? | Probably. Rosuvastatin (JUPITER) seems to be. Atorvastatin (ASCOT-LLA), Lovastatin (AFCAPS/TexCAPS) aren't clearly effective.
• In my patient with existing CAD, do I care about measuring their cholesterol levels?

References & Further Reading

1. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. JACC. 2016;68(1):92-125. doi:10.1016/j.jacc.2016.03.519
2. PCSK9 inhibitors may improve cardiovascular outcomes-Can we afford them? Int J Cardiol. 2016;220:242-245. doi:10.1016/j.ijcard.2016.06.126
3. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;0(0). doi:10.1016/S0140-6736(16)31357-5
4. Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. SAGE Publications; 2014 Mar 12;21(4):464–74.
5. Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation: Cardiovascular Quality and Outcomes. Lippincott Williams & Wilkins; 2013 Jul;6(4):390–9.
6. Lack of Evidence for Recommended Low-Density Lipoprotein Treatment Targets: A Solvable Problem. Ann Intern Med. 2006;145:520-530.
7. Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease. Ann Intern Med. 2010;152:69-77.
8. Shifting views on lipid lowering therapy. BMJ 2010;341:c3531
9. Three Reasons to Abandon Low-Density Lipoprotein Targets. Circ Cardiovasc Qual Outcomes. 2012;5:2-5.
10. Mancini GBJ, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference. The Canadian Journal of Cardiology 2011;27:635–62.
11. Leuschen J, et al. Association of Statin Use With Cataracts: A Propensity Score-Matched Analysis. JAMA Ophthalmol 2013;
12. Naci H, Brugts J, Ades T. Comparative Tolerability and Harms of Individual Statins : A Study-Level Network Meta-Analysis of 246 955 Participants From 135 Randomized Controlled Trials. Circ Cardiovasc Qual Outcomes 2013;6:00–0.
13. Saha SA, et al. 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;154:943-53
14. Cheung et al. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br J Clin Pharmacol 2004;57:640-51
15. Brugts et al. 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.
16. ENHANCE. N Engl J Med 2008;358:1431-43.
17. SEAS. NEJM 5SEP08
18. CTT-Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2008;371:117-25
19. CTTC-Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials
20. NLA Muscle Safety Expert Panel. Am J Cardiol 2006;97:69C-76C
21. Statin safety: a systematic review. Am J Cardiol 2006;97:52C-60C
22. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288:462-7
23. Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy. Cannon et al. JACC 2006;48:438-45

KEY TRIALS

HPS

TNT

JUPITER

ASCOT-LLA

SPARCL

CARDS