Cholesterol targets and therapy Thomas C. Andrews, MD, FACC
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Statins in secondary prevention Still first line therapy! First line therapy: high intensity statin Dose individualized based on baseline LDL Atorvastatin 40 or 80 Rosuvastatin 20 or 40 Second line therapies Statin intolerant or not near goal of LDL <70 mg/dl Ezetimibe plus statin PCSK9 inhibitors Monitoring Lipid panel at baseline and 6 weeks post med change Annual (or perhaps semiannual) lipid panels assess compliance! 3
Statin intolerance Patient one-liners I am allergic to all statins When I took that drug, I couldn t get out of bed Statins are bad for you My memory is bad enough I don t want to get diabetes Are clinicians developing statin-intolerance tolerance? 4
Relative risk reduction after MI All cause mortality 50 45 46 40 35 % mortality reduction 30 25 20 24 21 Smoking cessation Beta blocker Statin treatment 15 10 5 0 Secondary prevention 5
Statin side effects Myth or reality? Hepatitis Diabetes Cognitive dysfunction Renal failure Peripheral neuropathy Muscle symptoms 6
Statin associated hepatitis ALT>3x ULM/100,000 person-years Treatment Placebo Net risk Single measure 300 200 100 cases 2 consecutive measures 110 40 70 cases 7
Statins and diabetes Clinical trial data Statin Odds ratio (95% CI) Any statin (n=91 140) 1.09 (1.02 1.17) Atorvastatin (n=7773) 1.14 (0.89 1.46) Simvastatin (n=18 815) 1.11 (0.97 1.26) Rosuvastatin (n=24 714) 1.18 (1.04 1.33) Pravastatin (n=33 627) 1.03 (0.90 1.19) Lovastatin (n=6211) 0.98 (0.70 1.38) NNH to causes 1 case of DM: 250 NNT to prevent 1 episode of ACS: 25 Sattar N et al, Lancet 2010 8
Statins and renal failure Treatment N Creatinine % Change Change in GFR Placebo 371 0.8-0.3 Rosuvastatin Atorvastatin Simvastatin Pravastatin 5 mg 10 mg 20 mg 40 mg 10 mg 20 mg 40 mg 80 mg 10 mg 20 mg 40 mg 80 mg 10 mg 20 mg 40 mg 637 2909 1432 2107 1394 1562 221 535 161 1217 506 500 159 342 745-1.6-1.4-1.6-1.3-1.5-1.4-2.0-3.8-0.4-1.4-1.6-1.2-1.8-2.1-0.7 1.5 1.6 1.9 1.6 1.6 1.5 1.9 3.4 0.5 1.4 1.7 1.5 1.8 1.9 0.8 9
Statin associated peripheral neuropathy Cohort studies Anderson JL et al. Am J Cardiol. 2005;95:1097-1099 Corrao G et al. J Epidemiol Community Health. 2004;58:1047-1051 Gaist D et al. Neurology. 2002;58:1333-1337 Gaist D et al. Eur J Clin Pharmacol. 2001;56:931-933 ALL COHORT STUDIES 1.8 (1.1-3.4) 0 1 2 3 4 Odds Ratio 12 cases per 100,000 person years 5 10
Statins and cognitive function Observational studies Hajjar I et al. J Gerontol A Biol Sci Med Sci. 2002;57:408-414 Green RC et al. Neurobiol Aging. 2002;23:S273-S274 Jick H et al. Lancet. 2000;356:1627-1631 Rockwood K et al. Arch Neurol. 2002;59:223-227 Rodriquez EG et al. J Am Geriatr Soc. 2002;50:1852-1856 Wolozin B et al. Arch Neurol. 2000;57:1439-1443 Yaffe K et al. Arch Neurol. 2002;59:378-384 ALL COHORT STUDIES 0.43 (0.31-0.62) Etminan et al. Pharmacotherapy. 2003;23:726-730 0 1 11 2
Statins and dementia Neuropsychiatric testing in heart protection study (simvastatin) Measure Simvastatin Placebo Cognitive impairment 23.7% 24.2% Dementia 0.3% 0.3% Psychiatric disorder 0.7% 0.7% Suicide 0.1% 0.1% 12
Statin Associated Myopathy Clinical Spectrum Myalgia Common: 10-20% Musculoskeletal symptoms with normal CK Myositis Uncommon: <1% Musculoskeletal symptoms, CK<3x ULN Myopathy Rare: <0.01% Musculoskeletal symptoms, CK 3-10x ULN Rhabdomyolysis 1 per 1 million prescriptions Musculoskeletal symptoms, CK>10x ULN 13
Statin myopathy Management Assess for drug interactions Most common with lovastatin & simvastatin (P-450 3A4) Grapefruit juice >8 oz/day Amlodipine, Amiodarone, others Fenofibrate instead of gemfibrozil Watch protease inhibitors, cyclosporine Assess for Vit D deficiency and hypothyroidism Consider dose reduction/trial of pravastatin Consider alternate day dosing Pravastatin QOD Atorvastatin or rosuvastatin weekly No outcomes data! 14
PCSK9 inhibitors Proprotein convertase subtilisin/kexin type 9 Alirocumab (Praluent) and evolocumab (Repatha) monoclonal antibodies Lower LDL by 60% Reduce Lp(a) up to 36% Regression of plaque volume Prevention of MI and stroke Probable reduction in mortality (meta-analysis) Administration subq 1-2 times a month Side effects (no muscle toxicity!) Hypersensitivity and site reactions GI (diarrhea) Neurocognitive decline? 15
PCSK9 Inhibitors Mechanism of action 16
Statins in clinical practice Summary An important part of our armamentarium Serious side effects uncommon Intolerance common Start with a high intensity statin and modify based on subsequent on-treatment LDL levels?add zetia?role of PCSK9 inhibitors PCSK9 inhibitors provide an alternative Expensive! Emerging long term outcomes data 17