Cholesterol targets and therapy Thomas C. Andrews, MD, FACC

Transcription

1 Cholesterol targets and therapy Thomas C. Andrews, MD, FACC

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3 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

4 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

5 Relative risk reduction after MI All cause mortality % mortality reduction Smoking cessation Beta blocker Statin treatment Secondary prevention 5

6 Statin side effects Myth or reality? Hepatitis Diabetes Cognitive dysfunction Renal failure Peripheral neuropathy Muscle symptoms 6

7 Statin associated hepatitis ALT>3x ULM/100,000 person-years Treatment Placebo Net risk Single measure cases 2 consecutive measures cases 7

8 Statins and diabetes Clinical trial data Statin Odds ratio (95% CI) Any statin (n=91 140) 1.09 ( ) Atorvastatin (n=7773) 1.14 ( ) Simvastatin (n=18 815) 1.11 ( ) Rosuvastatin (n=24 714) 1.18 ( ) Pravastatin (n=33 627) 1.03 ( ) Lovastatin (n=6211) 0.98 ( ) NNH to causes 1 case of DM: 250 NNT to prevent 1 episode of ACS: 25 Sattar N et al, Lancet

9 Statins and renal failure Treatment N Creatinine % Change Change in GFR Placebo 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

10 Statin associated peripheral neuropathy Cohort studies Anderson JL et al. Am J Cardiol. 2005;95: Corrao G et al. J Epidemiol Community Health. 2004;58: Gaist D et al. Neurology. 2002;58: Gaist D et al. Eur J Clin Pharmacol. 2001;56: ALL COHORT STUDIES 1.8 ( ) Odds Ratio 12 cases per 100,000 person years 5 10

11 Statins and cognitive function Observational studies Hajjar I et al. J Gerontol A Biol Sci Med Sci. 2002;57: Green RC et al. Neurobiol Aging. 2002;23:S273-S274 Jick H et al. Lancet. 2000;356: Rockwood K et al. Arch Neurol. 2002;59: Rodriquez EG et al. J Am Geriatr Soc. 2002;50: Wolozin B et al. Arch Neurol. 2000;57: Yaffe K et al. Arch Neurol. 2002;59: ALL COHORT STUDIES 0.43 ( ) Etminan et al. Pharmacotherapy. 2003;23:

12 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

13 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

14 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

15 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

16 PCSK9 Inhibitors Mechanism of action 16

17 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