Hospitalist Ronald Witteles, M.D. Stanford University School of - PDF document

“ Cardiology Pearls for the Hospitalist ” Ronald Witteles, M.D. Stanford University School of Medicine October 20, 2018 @Ron_Witteles Outline  A common patient scenario… – It might seem standard but… – Can we do better?  News hot off the presses  A diagnosis not to be missed anymore… and one you certainly see!  Final thoughts 1

A Familiar Patient 78 y.o. man with dilated nonischemic • cardiomyopathy Diagnosis: 4 years ago, normal coronary • angiogram, LBBB present Echo at diagnosis (not significantly changed • since then): Moderately dilated LV, LVEF 25%, 3+ MR Course over 4 years: • • 3 hospitalizations for ADHF (last 6 months ago) • Generally adherent with meds • Usually NYHA 2-3 symptoms • BP typically runs in 105/70 range • NT-proBNP 4 months ago = 3000 pg/ml Outpatient Medications Furosemide 40 mg bid • Metoprolol tartrate 25 mg bid • Lisinopril 10 mg qd • Digoxin 0.5 mg qd • Rosuvastatin 10 mg qhs • KCl 20 mEq qd • 2

A Familiar Patient Now – admitted to hospital • • 7 kg weight gain over last 3 weeks • Worsening DOE, now SOB with a few steps • No chest pain, dizziness, or any other symptoms Exam & Labs Exam (pertinent): • • Afebrile, HR 72, BP 105/70, RR 16, SaO2 95% RA • JVP 15 cm H2O • Laterally displaced PMI, RRR with 2/6 systolic murmur at apex • Scattered bibasilar rales • 3+ bilateral LE edema Labs: • • Na 136, K 4.4 • BUN 26, Cr 1.4 (baseline 1.4) • NT-pro-BNP 6500 pg/mL • Troponin I: <0.1 • Digoxin: 0.9 (therapeutic) • Lipids: LDL 115, HDL 45, TG 115 3

Hospital Course EKG/Echo – EF 25%, 3+MR, LBBB (similar to baseline) • Diuresed with IV furosemide over 4 days • Symptoms improve to close to baseline • Discharged home – same meds, augmented furosemide/K • Labs on day of discharge: • • Na 134 • K 4.2 • BUN 35 • Cr 1.6 • NT-pro-BNP 5500 pg/ml • Digoxin 0.9 (therapeutic) Could we have done any better for this patient? • What Do You Do? What about the lisinopril? 1) Continue lisinopril unchanged 2) Uptitrate lisinopril dose to 20 mg qd 3) Change lisinopril to ARB 4) Stop lisinopril & start sacubitril/valsartan next day 5) Change lisinopril to ARB x 36 hours, then change to sacubitril/valsartan 4

What Do You Do? What about the lisinopril? 1) Continue lisinopril unchanged 2) Uptitrate lisinopril dose to 20 mg qd 3) Change lisinopril to ARB 4) Stop lisinopril & start sacubitril/valsartan next day 5) Change lisinopril to ARB x 36 hours, then change to sacubitril/valsartan PARADIGM-HF Neprilysin: Breaks down natriuretic peptides & • angiotensin II Trial: Sacubitril-valsartan vs. Enalapril • Double-blind, randomized trial of 8442 patients • • LVEF ≤ 40% • NYHA II-IV Primary end-point: Time to CV death or HF • hospitalization Stopped early after median follow-up of 27 months • • ACC/AHA/HFSA Guidelines: • SWITCH NYHA Class 2-3 HFrEF patients from ACEi or ARB to sacubitril-valsartan (Class 1 recommendation!) Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. 5

Breakdown of Outcomes Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. Breakdown of Outcomes Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. 6

Breakdown of Outcomes Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. What You Should Be Asking Yourself… Which systolic HF patients should I not be putting on sacubitril/valsartan? 7

Practicalities of Use • Greater BP drop than with ACEi or ARB alone • Must be off of ACEi for at least 36 hours (angioedema risk) • All the more reason to get away from ACEi for new heart failure patients • Make sure insurance approval in place! Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. What Should You Do with the Metoprolol 25 mg bid? 1) Stop the beta-blocker (ADHF admission) 2) Change to carvedilol 6.25 mg bid 3) Change to carvedilol 25 mg bid 4) Continue metoprolol tartrate 25 mg bid 5) Change to metoprolol succinate 50 mg qd 8

What Should You Do with the Metoprolol 25 mg bid? 1) Stop the beta-blocker (ADHF admission) 2) Change to carvedilol 6.25 mg bid 3) Change to carvedilol 25 mg bid 4) Continue metoprolol tartrate 25 mg bid 5) Change to metoprolol succinate 50 mg qd COMET Trial 3029 patients • • LVEF < 35% • NYHA Class II-IV • HF Admission within last 2 years Randomized to: • • Carvedilol 3.125 mg bid  25 mg bid vs. • Metoprolol tartrate 5 mg bid  50 mg bid Mean follow-up: 4.8 years • 9

COMET: Mortality P= 0.0017 Adapted from Poole-Wilson et al. Lancet. 2003;362:7-13. COMET: Heart Rates Adapted from Poole-Wilson et al. Lancet. 2003;362:7-13. 10

What should you do with the digoxin 0.5 mg/day? 1) Get rid of it. 2) Continue at a lower dose. 3) Continue unchanged. What should you do with the digoxin 0.5 mg/day? 1) Get rid of it. 2) Continue at a lower dose. 3) Continue unchanged. 11

Digoxin – DIG Trial (1997) • 6800 patients with EF ≤ 45% • Digoxin vs. placebo • All patients in sinus rhythm • Outcomes: • Primary: All-cause mortality • Secondary: CV death, worsened HF & hospitalizations All-Cause Mortality Adapted from NEJM. 1997;336:525-33. 12

Death or HF Hospitalization placebo digoxin Adapted from NEJM. 1997;336:525-33. Cochrane Review: Risk of Clinical Deterioration if Stop Dig Adapted from Hood et al. Cochrane Library. 2004, Issue 4. 13

An Inevitable Sequence of Events... Well-meaning physician targets digoxin levels for • treatment of HF or atrial fibrillation A patient with eggerthella lenta ends up on an • extremely high dose of digoxin Patient receives antibiotics (Z-pack, etc.) • Patient gets dig-toxic • NOTE: This is the reason for antibiotic-digoxin • medication interactions! How to Avoid This? Step 1: Recognize we live in a world of antibiotics. • • It is not realistic to think your patient will not ultimately get an antibiotic prescription. Step 2: Don’t target digoxin levels! • • You can estimate daily dose by 2 main things: • GFR • Amiodarone use • Nobody should require a maintenance dose > 0.25 mg • Remember: For the most part, low levels are okay! • Particularly true if using for heart failure indication rather than rate control Reasons for checking digoxin levels: • • You suspect toxicity • To check medication adherence 14

DIG Trial: Post-hoc Analysis of Mortality vs. 1-month Digoxin Levels Adapted from Adams et al. J Am Coll Cardiol. 2005;46:497-504. What Should You Do With the Rosuvastatin 10 mg? 1) Get rid of it. 2) Continue rosuvastatin 10 mg 3) Increase to rosuvastatin 40 mg 4) Switch to atorvastatin 40 mg 5) Switch to PCSK9 inhibitor 15

What Should You Do With the Rosuvastatin 10 mg? 1) Get rid of it. 2) Continue rosuvastatin 10 mg 3) Increase to rosuvastatin 40 mg 4) Switch to atorvastatin 40 mg 5) Switch to PCSK9 inhibitor GISSI-HF Trial 4574 patients with HF (ischemic or nonischemic) • • NYHA Class II-IV • EF <40% or EF>40% but HF hospitalization in past 12 months • Ischemic (40%), Nonischemic (60%) Randomized: Rosuvastatin 10 mg daily vs. • placebo Primary endpoints: • • Survival • Mortality or CV hospitalization Adapted from GISSI-HF Investigators. Lancet. 2008;372:1231-9. 16

GISSI-HF: Mortality Adapted from GISSI-HF Investigators. Lancet. 2008;372:1231-9. GISSI-HF: Mortality or CV Hospitalization Adapted from GISSI-HF Investigators. Lancet. 2008;372:1231-9. 17

A Mental Exercise You’re a highly-paid executive at a big • pharmaceutical company which makes an on-patent statin. You have been tasked with designing a heart failure • clinical trial to test your statin’s efficacy. • #1 concern: Get a positive result! What type of study would you pitch? • • Large • Placebo-controlled (not versus alternative lipid- lowering agent!) • Only patients with ischemic cardiomyopathy • Primary endpoint: Vascular events! Only one problem… • • No way this would ever be considered ethical… • Right? CORONA 5011 patients ≥ 60 years • All with ischemic, systolic HF • • NYHA II: EF ≤ 35% • NYHA III-IV: EF ≤ 40% Rosuvastatin 10 mg daily vs. placebo • Primary endpoint : A vascular endpoint (!) • • CV death, nonfatal MI, nonfatal stroke 18

CORONA: Primary Endpoint Adapted from Kjekshus et al. NEJM. 2007;357:2248-61. CORONA: All-Cause Mortality Adapted from Kjekshus et al. NEJM. 2007;357:2248-61. 19

So What to Do With Statins in HF? For nonischemic heart failure  forget it! • For ischemic heart failure… • • If angina, PVD, etc.  still use • Otherwise  consider not using • Polypharmacy issues are real! • Let’s focus on what makes a real difference… You are doubling the outpatient furosemide & plan to check a BMP within 5 days of discharge. What should you do with the potassium? 1) Get rid of it. 2) Increase KCl to 40 mEq/day. 3) Switch to spironolactone. 20