Non Statin Therapy for Hyperlipidemia 2024 Student PDF

Mark Stephens, PharmD, BCPS 1. Recognize or describe the mechanism of action of ezetimibe, PCSK9 mAbs, bempedoic acid, inclisiran, and evinacumab 2. Identify the impact of non-statin therapies on LDL, HDL, and TG 3. Identify the impact of non-statin therapies ASCVD outcomes 4. Place in...

Mark Stephens, PharmD, BCPS 1. Recognize or describe the mechanism of action of ezetimibe, PCSK9 mAbs, bempedoic acid, inclisiran, and evinacumab 2. Identify the impact of non-statin therapies on LDL, HDL, and TG 3. Identify the impact of non-statin therapies ASCVD outcomes 4. Place in order of use the non-statin therapies recommended in the four statin benefit groups 5. Recognize key components in the definition of persistent hypertriglyceridemia 6. Identify or list common secondary causes of hypertriglyceridemia 7. Identify the patient populations likely to benefit from icosapent ethyl  Adults ≤ 75 yo Adults 20-75 yo, with clinical ASCVD LDL ≥ 190 mg/dl High Intensity Statin High Intensity Statin Need Statins Adults 40-75 yo, Adults 40-75 yo, diabetes, LDL > 70 < 189 mg/dl, LDL > 70 mg/dl 10-yr ASCVD risk ≥5.0% Moderate – High Intensity Statin Moderate – High Intensity Statin  HeFH or Statin HoFH Intolerance Insufficient Response Non- Hypertriglyceridemia statin Therapy Ezetimibe PCSK9 mAb Bile Acid Sequestrants Icosapent ethyl Bempedoic acid Inclisiran Evinacumab Fibrates Niacin   Inhibits cholesterol absorption at the brush border of the small intestine  Targets NPC1L1 receptor  Decreases delivery of cholesterol to the liver  Decreases hepatic cholesterol stores  Decreases LDL Image: https://www.youtube.com/watch?v=d48PsT7zeA8. Accessed September 2024  Study Design R, DB Patients 18,144 patients with ACS within 10 days, LDL 50-100 mg/dl if on meds, 50-125 mg/dl if not on meds. Randomized to: Simvastatin 40 mg + ezetimibe 10 mg daily Simvastatin 40 mg x 6 yrs Primary Outcome Composite: CV death, nonfatal MI, nonfatal CVA, UA w hospitalization, coronary revascularization Results Sim + Ezetimibe Simvastatin HR P-value Primary 32.7% 34.7% 0.936 0.016 Nonfatal MI 12.8% 14.4% 0.87 0.002 Ischemic CVA 3.4% 4.1% 0.79 0.008 N Engl J Med 2015;372:2387-97. Ezetimibe added to statins reduces MACE Evolocumab Alirocumab   PCSK9  LDL receptor numbers by blocking recycling  mAb binds to PCSK9  Inhibits PCSK9 from binding to LDL-receptors  Increases LDL-receptors by increasing receptor recycling  Increased LDL receptor numbers leads to decreased plasma LDL Image: https://www.researchgate.net/figure/PCSK9-inhibitors-mechanism-of-action-A-PCSK9-is-primarily-secreted- in-the-liver-and_fig1_335918960. Accessed September 2022  Study Design R, DB, PC, 1242 centers, 49 countries Patients 27,564 patients WITH ASCVD LDL ≥ 70 mg/dl on statins (69% on high-intensity) Medications Evolocumab 140 mg SubQ q 2 weeks or 420 mg SQ monthly Placebo Primary Outcome Composite of CV death, MI, CVA, hospitalization for unstable angina, coronary revascularization Secondary Composite of CV death, MI, CVA Outcome Follow-up 2.2 years N Engl J Med 2017;376:  Evolocumab Placebo HR P-value Primary Endpoint 9.8% 11.3% 0.85