Cardiology Practice Updates

1. Cardiology Practice Updates Sharolyn Cook, D.O., FACOI OSU assistant professor department of internal medicine

2. Disclosure • I have no relevant financial relationships or affiliations with commercial interests to disclose.

3. Cardiology Practice Updates • 2018 Cholesterol Guideline Update • Stents and anti-platelet duration • Wearable technologies • New Aspirin recommendations

7. Don’t worry, I read the 120 page document

8. In patients with clinical ASCVD, reduce low-density lipoprotein cholesterol (LDL-C) with high-intensity statin therapy or maximally tolerated statin therapy. The more LDL-C is reduced on statin therapy, the greater will be subsequent risk reduction. Use a maximally tolerated statin to lower LDL-C levels by ≥50%.

9. In very high-risk ASCVD, use a LDL-C threshold of 70 mg/dL (1.8 mmol/L)to consider addition of nonstatins to statin therapy. • Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. • In very high-risk ASCVD patients, it is reasonable to add ezetimibe to maximally tolerated statin therapy when the LDL-C level remains ≥70 mg/dL (≥1.8 mmol/L). • In patients at very high risk whose LDL-C level remains ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable, although the long-term safety (>3 years) is uncertain and cost- effectiveness is low at mid-2018 list prices.

10. In patients with severe primary hypercholesterolemia (LDL-C level ≥ 190 mg/dL[≥4.9 mmol/L]) without calculating 10-year ASCVD risk, begin high-intensity statin therapy without calculating 10-year ASCVD risk. •If the LDL-C level remains ≥100 mg/dL (≥2.6 mmol/L), adding ezetimibe is reasonable• If the LDL-C level on statin plus ezetimibe remains ≥100 mg/dL (≥2.6 mmol/L) & the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considered, although the long-term safety (>3 years) is uncertain and economic value is low at mid-2018 list prices.

11. In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL (≥1.8 mmol/L), at a 10-year ASCVD risk of ≥7.5%, start a moderate-intensity statin if a discussion of treatment options favors statin therapy. Risk-enhancing factors favor statin therapy (see No. 8).If risk status is uncertain, consider using coronary artery calcium (CAC) to improve specificity (see No. 9).If statins are indicated, reduce LDL-C levels by ≥30%, and if 10-year risk is ≥20%, reduce LDL-C levels by ≥50%.

12. In adults 40 to 75 years of age without diabetes mellitus and 10-year risk of 7.5% to 19.9% (intermediate risk), risk-enhancing factors favor initiation of statin therapy (see No. 7).Risk-enhancing factors include • family history of premature ASCVD; • persistently elevated LDL-C levels ≥160 mg/dL (≥4.1 mmol/L); • metabolic syndrome; • chronic kidney disease; • history of preeclampsia or premature menopause (age <40 yrs) • chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, or chronic HIV);• high-risk ethnic groups (e.g., South Asian); • persistent elevations of triglycerides ≥ 175 mg/dL (≥1.97 mmol/L);

13. In adults 40 to 75 years of age without diabetes mellitus and 10-year risk of 7.5% to 19.9% (intermediate risk), risk-enhancing factors favor initiation of statin therapy (see No. 7).Risk-enhancing factors include • apolipoprotein B ≥130 mg/dL • high-sensitivity C-reactive protein ≥2.0 mg/L • ankle-brachial index <0.9 • lipoprotein (a) ≥50 mg/dL or 125 nmol/L, especially at higher values of lipoprotein (a). Risk-enhancing factors may favor statin therapy in patients at 10-year risk of 5-7.5% (borderline risk)

14. In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain, consider measuring CAC. • If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD. • A CAC score of 1 to 99 favors statin therapy, especially in those ≥55 years of age. • For any patient, if the CAC score is ≥100 Agatston units or ≥75th percentile, statin therapy is indicated unless otherwise deferred by the outcome of clinician–patient risk discussion.

15. Assess adherence and percentage response to LDL-C–lowering medications and lifestyle changes with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed. •Defineresponses to lifestyle and statin therapy by percentage reductions in LDL-C levels compared with baseline. • In ASCVD patients at very high-risk, triggers for adding nonstatin drug therapy are defined by threshold LDL-C levels ≥70 mg/dL (≥1.8 mmol/L) on maximal statin therapy (see No. 3).

16. ASCVD calculator • http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/

17. Reminder for the Statins

18. Lab: Not Necessarily Fasting If an individual has ingested an extremely high-fat meal in the preceding 8 hours, it may be prudent to assess lipids on another day after counseling the patient to avoid such meals. Documentation of the baseline LDL-C level will be useful in assessing the patient’s response to the initiation of statin therapy, if that is undertaken. Similarly, given relatively modest differences in LDL-C levels associated with the postprandial state, use of a nonfasting sample is effective to document baseline lipid levels before initiation of statin therapy in individuals with clinical ASCVD. In adults with a family history of premature ASCVD or genetic hyperlipidemia, a fasting lipid profile is reasonable for initial evaluation.

19. CT Coronary Calcium Score

20. CT Coronary Calcium Score

23. Use of the CAC to Help Increase Risk Prediction

24. Patient Case • 47 M Father MI at 56 LDL 165 HDL 40normotensive non-diabeticnon-smokerexercises 3-5 Xa week BMI 24 • CAC 19 all in pLAD • Estimate Risk3.2% LowCurrent 10-Year ASCVD Risk • Lifetime ASCVD Risk:    46%

25. Guideline Practice Change: Dual Antiplatelet Therapy (DAPT) DAPT is mandatory early after drug-eluting stent placement Endothelialization of the stent normally occurs during the first 7 to 30 days after placement (mortality rate of acute stent thrombosis is between 9% and 45% ) Aspirin 75 to 100 mg has been shown to be effective as secondary prevention of atherosclerotic disease and is recommended lifelong in this clinical setting. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused \update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiol- ogy/American Heart Association Task Force on Clinical PracticeGuidelines. Circulation 2016; 134

26. Multiple DAPT Studies…

28. When DAPT score is ≥2, the number needed to treat (NNT) to prevent an ischemic event was 33 and the number needed to harm (NNH) with a bleeding event was 263. When the DAPT score is <2, NNT to prevent an ischemic event climbs to 169 and NNH to cause a bleeding complication drops to 69.

30. Meta-analysis of Length of DAPT

31. DAPT Risk Calculator - American College of Cardiology

32. MI Percentage Thienopyridinevs Placebo

33. Total Mortality Thienopyridinevs Placebo

37. True Atrial Fibrillation Burden ?Palpitations? Cryptogenic stroke?

38. Apple Heart Study: Apple with Standford The primary endpoints were AFib >30 seconds on ECG patch and simultaneous AFibon ECG patch (worn for 7 days) and tachogram. Less than 0.5% had notifications of abnormal heart rhythm. They detected afib in 34% of those patients

39. Kardiadevice

42. You Choose…

43. Aspirin Evidence: Primary Prevention BDT, 1988 RR of MI in Men RR of CVA in Men PHS, 1989 TPT, 1998 HOT, 1998 PPP, 2001 RR = 0.68 (0.54-0.86)P=0.001 RR = 1.13 (0.96-1.33)P=0.15 Combined 5.0 0.2 0.5 1.0 2.0 0.2 0.5 1.0 2.0 5.0 RR of MI in Women RR of CVA in Women HOT, 1998 PPP, 2001 WHS, 2005 RR = 0.99 (0.83-1.19)P=0.95 RR = 0.81 (0.69-0.96)P=0.01 Combined 5.0 0.2 0.5 1.0 2.0 0.2 0.5 1.0 2.0 5.0 Aspirin Better Placebo Better Aspirin Better Placebo Better CVA=Cerebrovascular accident, MI=Myocardial infarction, RR=Relative risk Source: Ridker P et al. NEJM 2005;352:1293-1304

44. Aspirin Evidence: Primary Prevention Antithrombotic Trialists’ (ATT) Collaboration Meta-analysis of 95,456 low risk patients randomized to aspirin (100 mg every other day to 500 mg daily) vs. placebo for 3.7-10 years Aspirin reduces the risk of ischemic events, but with a higher rate of bleeding Source: Antithrombotic Trialists’ Collaboration. Lancet 2009;373:1849-1860

47. Primary prevention is different than secondary prevention. Aspirin is beneficial in patients with prior ischemic events i.e. MI, CVA, symptomatic PAD

48. Aspirin Evidence: Secondary Prevention Effect of antiplatelet treatment* on vascular events** Category% Odds Reduction Acute MI Acute CVA Prior MI Prior CVA/TIA Other high risk CVD(e.g. unstable angina, heart failure) PAD(e.g. intermittent claudication) High risk of embolism (e.g. Afib) Other (e.g. DM) All trials 2.0 0.0 0.5 1.0 1.5 Antiplatelet better Control better Aspirin reduces the risk of adverse cardiovascular events *Aspirin was the predominant antiplatelet agent studied **Include MI, stroke, or death Source: Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86

49. STOPDAPT-2 #ACC19 Trial Description: Patients undergoing PCI were randomized to 1 month of DAPT followed by clopidogrel monotherapy for 5 years versus 12 months of DAPT followed by aspirin monotherapy for 5years. RESULTS (p =0.04) • Primary outcome, death, MI, stent thrombosis, stroke, TIMI major/minor bleeding at 1 year: 2.4% of 1-month DAPT group compared with 3.7% of 12-month DAPT group (p for superiority =0.04) • Death, MI, stent thrombosis, or stroke at 1 year: 2.0% of 1-month DAPT group compared with 2.5% of 12-month DAPT group (p for noninferiority =0.005) 3.7 4 2.4 2 % CONCLUSIONS • Among patients undergoing PCI for stable and unstable cardiovascular disease, 1- month DAPT followed by clopidogrel monotherapy was superior to 12-month DAPT followed by aspirin monotherapy at preventing net adverse clinicalevents • 1-month DAPT was noninferior to 12-month DAPT at preventing major adverse ischemicevents 0 Primaryendpoint 12- month DAPT, followed byaspirin monotherapy (n =1,522) 1-monthDAPT, followed by clopidogrel monotherapy (n =1,523) Presented by Dr. Hirotoshi Watanabe at ACC2019

50. Questions? Triple therapy? Entresto? BP goals? Structural heart disease? Low dose Xarelto? New Eliquis trial? 1111 West 17th Street Tulsa, Oklahoma 74107 (918) 561-1100 www.osumedicine.com