Case Studies The Role of Non-Statin Therapies for LDL-C Lowering in the Management of ASCVD Risk

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1 Case Studies The Role of Non-Statin Therapies for LDL-C Lowering in the Management of ASCVD Risk Kim K. Birtcher, PharmD, MS, AACC Clinical Professor University of Houston College of Pharmacy Houston, Texas

2 Case 1 49-year old man presents for follow-up in the clinic PMH: hypercholesterolemia, chronic stable angina States adherence to atorvastatin 20 mg (and other meds) + lifestyle modifications BMI 32 kg/m 2 (stable for 3 years) LDL-C has 42% from baseline On-treatment LDL-C = 115 mg/dl

3 Which of the following do you recommend? A. Pt is intolerant to statin therapy. Stop atorvastatin. B. Pt had less-than-anticipated response on moderate-intensity statin. Start ezetimibe. C. Pt had anticipated response to moderate-intensity statin. Try alternate high-intensity statin therapy prior to adding nonstatin. D. Clinician and pt should consider potential net ASCVD riskreduction benefit of adding non-statin & pt preferences.

4 Stable Clinical ASCVD Without Comorbidities Comorbidities diabetes recent (<3 mo) acute ASCVD event ASCVD event while on statin baseline LDL-C 190 mg/dl uncontrolled major risk factors elevated Lp(a) CKD J Am Coll Cardiol 2016;68:92 125

5 Stable Clinical ASCVD Without Comorbidities On maximally tolerated statin Achieved threshold? 50% LDL-C reduction (May consider LDL-C <100 mg/dl) If not, 1 st consider adding: Ezetimibe (may consider BAS if ezetimibe intolerant + TG <300 mg/dl) If not, 2 nd consider adding: PCSK9 inhibitor in addition or as replacement for ezetimibe Comorbidities = diabetes, recent acute ASCVD event, ASCVD event while on statin, baseline LDL-C 190 mg/dl, uncontrolled major risk factors, elevated Lp(a), chronic kidney disease J Am Coll Cardiol 2016;68:92 125

6 Case 2 59-year old woman admitted for acute MI PMH: hypercholesterolemia, prior NSTEMI States adherence to atorvastatin 80 mg (and other meds) + lifestyle modifications LDL-C has 51% from baseline LDL-C 90 mg/dl

7 Which of the following do you recommend? A. Pt has achieved acceptable LDL-C reduction. No modifications to therapy are needed. B. Pt should receive moderate-intensity statin + ezetimibe. C. Pt should receive statin + niacin extended-release. D. Clinician and pt should consider potential net ASCVD risk-reduction benefit of adding non-statin & pt preferences.

8 Clinical ASCVD with Comorbidities On maximally tolerated statin Achieved threshold? 50% LDL-C reduction (May consider LDL-C <70 mg/dl or non-hdl-c <100 in pts with diabetes) If not, 1 st consider adding: Ezetimibe (may consider BAS if ezetimibe intolerant + TG <300 mg/dl) If not, 2 nd consider adding: PCSK9 inhibitor in addition or as replacement for ezetimibe Comorbidities = diabetes, recent acute ASCVD event, ASCVD event while on statin, baseline LDL-C 190 mg/dl, uncontrolled major risk factors, elevated Lp(a), chronic kidney disease J Am Coll Cardiol 2016;68:92 125

9 Case 3 38-year old man presents for follow-up in the clinic PMH: hypercholesterolemia, hypertension FH: premature ASCVD events, hypercholesterolemia States adherence to rosuvastatin 40 mg + lifestyle modifications Recently lost 10 pounds with lifestyle modifications LDL-C: Baseline 284 mg/dl, current 141 mg/dl (~50% LDL-C reduction)

10 Which ONE of the following non-statin therapies would you consider during patient-clinician discussion? A. Add colesevelam B. Add ezetimibe or a PCSK9 inhibitor C. Add lomitapide D. Add phytosterols E. Non-statin therapy is not indicated.

11 Baseline LDL-C 190 mg/dl (no Clinical ASCVD) Same initial clinical steps Achieved threshold? 50% LDL-C reduction (May consider LDL-C <100 mg/dl) If not, consider either ezetimibe OR PCSK9 inhibitor Referral to lipid specialist recommended (may consider mipomersen, lomitapide, LDL apheresis in appropriate pts) J Am Coll Cardiol 2016;68:92 125

12 Case 4 62-year-old woman presents for follow-up in the clinic PMH: diabetes, hypertension States adherence to atorvastatin 40 mg + lifestyle modifications LDL-C: Baseline 174 mg/dl, current 108 mg/dl ( 38%) Non-HDL-C: Current 153 mg/dl Triglycerides: 324 mg/dl 10-yr ASCVD risk > 7.5% The pt is willing to take additional medication to lower ASCVD risk.

13 At which of the following thresholds should the addition of non-statin therapy be considered in patient with DM and >7.5% ASCVD risk? A. LDL-C > 70 mg/dl B. LDL-C > 100 mg/dl C. Non-HDL-C > 100 mg/dl D. LDL-C reduction of only 55% from baseline

14 Which of the following do you recommend? A. Pt has achieved anticipated response to high-intensity statin & no other interventions are needed. B. Increase atorvastatin to 80 mg to achieve >50% LDL-C reduction. C. Preferentially consider colesevelam to lower LDL-C & A1C. D. Add fenofibrate 145 mg daily to reduce triglycerides to <150 mg/dl.

15 Ages (no Clinical ASCVD) + Diabetes Same initial clinical steps On moderate- or high-intensity statin Increase to high-intensity statin if needed Achieved threshold? Expected % LDL-C reduction Moderate-intensity: 30-<50%; high-intensity >50% (May consider LDL-C <100 mg/dl or non-hdl-c <130 mg/dl) If not, consider adding ezetimibe (may consider BAS if ezetimibe intolerant + TG <300 mg/dl) PCSK9 inhibitor is not indicated J Am Coll Cardiol 2016;68:92 125

16 Case 5 69-year-old woman referred with hypercholesterolemia Mild hypercholesterolemia prior to menopause with LDL-C levels gradually increasing with age 114 mg/dl in her 30s 138 mg/dl in her 40s 156 mg/dl in her 50s 178 mg/dl at time of presentation Initiated therapy with atorvastatin 20 mg but reports worsening of pain associated with rheumatoid arthritis

17 What is your initial approach to management of this patient? A. Discontinue treatment with atorvastatin and begin ezetimibe 10 mg daily. B. Discontinue treatment with atorvastatin and begin PCSK9 inhibitor due to baseline LDL-C >160 mg/dl. C. Temporarily stop treatment with atorvastatin and re-challenge at a lower dose. D. Advise patient that statin therapy is not associated with jointrelated symptoms and refer for management options for RA.

18 Case 6 48-year-old man is referred for recommendations for lipid therapy New diagnosis of non-ischemic cardiomyopathy with LVEF 33% Baseline LDL-C 142 mg/dl 10-year ASCVD risk 3.8% Currently on evidence-based therapy for HFrEF

19 What is your recommendation for lipid management of this patient? A. Initiate high-intensity statin. B. Discuss lifestyle interventions for LDL-C lowering. C. Initiate moderate-intensity statin therapy. D. Initiate moderate-intensity simvastatin in combination with ezetimibe.

20 Statin Therapy in Heart Failure In light of the aforementioned considerations, the approach to patients with ASCVD and NYHA functional class II to III heart failure due to ischemic heart disease should generally follow the algorithm for patients with ASCVD and comorbidities, with the exception that use of a PCSK9 inhibitor is not recommended at this time. Decisions about the use of other non-statin agents in these patients is a matter of clinical judgment after consideration of the potential net clinical benefit in the context of the patient s projected longevity and other comorbidities. J Am Coll Cardiol 2016;68:92 125

21 Case 7 32-year-old woman with familial hypercholesterolemia is referred for recommendations for lipid therapy Recently discontinued oral contraception to begin IVF treatment Baseline LDL-C 296 mg/dl Current therapy: Rosuvastatin 40 mg daily Ezetimibe 10 mg daily Alirocumab 75 mg every 2 weeks

22 What do you recommend for lipid management of this patient during conception, pregnancy, and lactation? A. Reduce intensity of statin therapy to rosuvastatin 5 mg daily. Discontinue ezetimibe. Continue PCSK9 inhibitor. B. Discontinue rosuvastatin and PCSK9 inhibitor. Continue ezetimibe. C. Switch from rosuvastatin to pravastatin 10 mg daily. Discontinue ezetimibe and PCSK9 inhibitor. D. Discontinue statin, ezetimibe, and PCSK9 inhibitor. Colesevelam and LDL apheresis may be considered.

23 Management of dyslipidemia in pregnancy Statins should only be used in premenopausal women who are using effective contraception and are not nursing. Premenopausal women with ASCVD or baseline LDL-C >190 mg/dl often have underlying genetic lipid disorders, particularly familial hypercholesterolemia, and/or multiple poorly controlled risk factors. Women who are currently on lipid-lowering drugs should be advised to discontinue pharmacologic therapy, with the exception of BAS, generally at least 1 month and preferably 3 months before attempted conception, or immediately if the patient is already pregnant. Referral to a lipid specialist and RDN is strongly recommended. J Am Coll Cardiol 2016;68:92 125

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