lICENSE To Treat Failure: An updated approach

1. lICENSE To Treat Failure: An updated approach CDR Timothy Murray CHF Clinic Manager Internal Medicine Team Inpatient Pharmacy Clinical Coordinator Claremore Indian Hospital Clinical Assistant Professor University of Oklahoma Primary Care Cardiology Update April 9, 2011

2. Case #1 • PT is a 37 yo white male whom is being consulted to the Internal Medicine service today secondary to an CHF exacerbation. JS presented to the ER with a 5 day history of increased shortness of breath and 10 lb weight increase. • Symptoms started after a recent trip where a “poor” diet was consumed. • Family Hx: DM, CAD • Social Hx: negative • PMH: HTN, CAD • Medication prior to admission: • Atenolol 25mg BID, aspirin 81mg daily, fish oil 1000mg daily, tamsulosin 0.4mg daily, KCL 8meq daily, furosemide 20mg daily

3. Case #1 Vitals: BP- 152/77, HR-101, WT- 177lbs

4. Case #1 • Physical Exam: • CHEST/LUNGS: • Chest: Nontender • Lungs: RALES Bilateral mostly at right base, no wheezing • CARDOVASCULAR: • Cardiac: regular rate, regular rhythm, No murmur • Pulses: Equal, DIMINISHED Very diminished at feet. • Carotid: No bruit • JVD: + distended • Abd aorta: No Bruit • Lower ext: BILATERAL Edema of both legs mostly right side 3/4 and 2/4 at left.

5. Case #1 • PT is treated in the hospital for 3 days. Weight has decreased 15 lbs and he feels much better. PT is to be seen in the CHF clinic in 2weeks for medication adjustment, dietary education, and monitoring. Completed echocardiogram reveals an ejection fraction of 25% • PT returns to CHF clinic in 2wks with the following labs: PNBP: 3200

6. Case #1 • Based upon the above case what type of interventions would you have expected to have been performed? (during admission or in clinic) A. Continue all medications prior to admission B. Increase Atenolol, start an ace-inhibitor, & start an aldosterone antagonist C. DC atenolol, start metoprolol succinate, & start an ace-inhibitor D. DC atenolol, start carvedilol, & start an ace-inhibitor E. Just give up and discharge patient from clinic!!!

7. Heart failure (HF) is a major public health problem resulting in substantial morbidity and mortality Major cost-driver of HF is high incidence of hospitalizations1,2 JCAHO has initiated HF quality care indicators for hospitalized HF patients Heart Failure Background 1 1American Heart Association. 2003 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 2002.

8. Estimated Direct and Indirect Costs of Heart Failure in US Total Cost$25.8 billion Hospitalization$13.6 53% Nursing Home$3.5 14% 7% 8% 8% 10% Physicians/Other Professionals$1.8 Lost Productivity/Mortality* $2.1 Drugs/Other Medical Durables$2.7 Home Healthcare$2.1 *Lost future earnings of persons who will die in 2004, discounted by 3% AHA. Heart Disease and Stroke Statistics—2004 Update

9. Causes of Hospital Readmission for Congestive Heart Failure Over 2/3 of HF Hospitalizations Preventable Diet Noncompliance 24% Rx Noncompliance 24% 16% Inappropriate Rx 17% Other 19% Failure to Seek Care Annals of Internal Medicine 122:415-21, 1995

10. Why a Hospital-based System for HF Management? • Patients • Patient capture point • Have patient’s/family’s attention: “teachable moment” • Predictor of care in community • Hospital structure • Standardized processes / protocols / teams • Accrediting bodies for standards of care • Centers for Medicare and Medicaid Services—peer review organization

11. Benefits & Drawbacks of HF Disease Management Programs Benefits Drawbacks • Improved use of evidence- based therapy • Improved symptom status and functional capacity • Improved QOL • Reduction in hospitalization • Decrease in total medical costs Usual Care HF Disease Management Program Moser DK, Mann DL. Circulation. 2002;105:2810–2812.

12. How did we get into this CHF mess?? • Where did our process break down and why no reduction in hospitalizations or re-hospitalizations? • Sub-optimal utilization of guidelines • No standardization of care (standing orders) • No team approach to treating CHF • No increase in intensity of HF care after hospital discharge

13. How to get out of this CHF mess?? • National registry • Develop a treatment plan (protocol) • Utilize a team approach to treating CHF • Provide a comprehensive service to monitor & make clinical alterations with patient’s treatment plan • Provide patient education & training to involve patients in their treatment plan • Follow-up on patients discharged after a CHF admission to avoid re-admission: CHF Clinic!!!!!! • Implement & utilize national standards of care for CHF • GET UP TO DATE WITH THE CHF GUIDELINES! • Document – Document - Document!

14. CMS • Center of Medicaid & Medicare Services • Compliance rates for discharging CHF pts • Joint Commission/ACC/AHA • CHF Performance Measures

15. CMS • CHF Core Measures • 1. Documentation of discharge instructions • 2. Left ventricular function assessment • 3. Use of ACE-I or ARB in pts with left ventricular systolic failure • 4. Documentation of smoking cessation

16. CMS • Hospitals should strongly consider implementing a process of care to ensure these measures are obtained and proper documentation occurs. • The principal outcome measure of the ADHERE Registry was to assess overall hospital adherence to each of these measures for participating hospitals.

17. CMS • CMS 2009 Documentation privileges for pharmacists! • Electronic Health Record advantages • GIPRA Measures/Performance Improvements • 2010 CMS 30 day readmission policy changes • Beta Blockers?

18. Medications • Ace-Inhibitors • Beta-Blockers • Aldosterone Antagonists • ARBs • ISDN/Hydralazine • Diuretics • Digitalis • Antiplatelets • Statins • Fish Oils • Calcium Channel Blockers

19. Guidelines Never Die • CHF care driven by two sets of national guidelines • American College of Cardiology/American Heart Association • Heart Failure Society of America

20. Guidelines Never Die • Both organizations provide a set of detailed treatment guidelines for practitioners in an effort to optimize the management of chronic CHF. • Treatment guidelines provide an approach to practice evidence based medicine.

21. CHF National Guidelines • Heart Failure Society of America • www.hfsa.org • Last update: June 2010 • American College of Cardiology/American Heart Association • http://circ.ahajournals.org • Last update: April 2009

22. Guidelines • 2009 ACC/AHA recommendation for: “implementation of practice based guidelines utilizing multidisciplinary disease-management programs in efforts to assist in the treatment of patients with CHF”.

23. Guidelines • 2010 HFSA recommendation for: “patients recently hospitalized for HF & other patients at high risk for HF decompensation should be considered for comprehensive HF disease management.”

24. HFSA 2010 Practice Guideline (3.2)HF Risk Factor Treatment Goals Journal of Cardiac Failure Vol. 16 No. 6 2010

25. HFSA 2010 Practice Guideline (3.3-3.4)Prevention—ACEI and Beta Blockers • ACE inhibitors are recommended for prevention of HF in patients at high risk for this syndrome, including those with: • Coronary artery disease • Peripheral vascular disease • Stroke • Diabetes and another major risk factor Strength of Evidence = A • ACE inhibitors and beta blockers are recommended for all patients with prior MI.Strength of Evidence = A Journal of Cardiac Failure Vol. 16 No. 6 2010

26. Management of Patients with Known Atherosclerotic Disease But No HF • Treatment with ACE inhibitors decreases the risk of CV death, MI, stroke, or cardiac arrest. NEJM 2000;342:145-53 (HOPE) Lancet 2003;362:782-8 (EUROPA) Placebo HOPE Ramipril 22% rel. risk red. p < .001 EUROPA Placebo Perindopril 20% rel. risk red. p = .0003

27. Treatment of Post-MI Patients with Asymptomatic LV Dysfunction (LVEF ≤ 40%) • SAVE Study • All-cause mortality ↓19% • CV mortality ↓21% • HF development ↓37% • Recurrent MI ↓25% Mortality Rate Placebo Captopril 19% rel. risk reduction p = 0.019 Years Pfeffer et al. NEJM 1992;327:669-77

28. HFSA 2010 Practice Guideline (7.1, 7.7)Pharmacologic Therapy: ACE Inhibitors • ACE inhibitors are recommended for symptomatic and asymptomatic patients with an LVEF ≤ 40%. Strength of Evidence = A • ACE inhibitors should be titrated to doses used in clinical trials (as tolerated during uptitration of other medications, such as beta blockers). Strength of Evidence = C • ACE inhibitors are recommended as routine therapy for asymptomatic patients with an LVEF ≤ 40%. • Post MIStrength of Evidence = B • Non Post-MIStrength of Evidence = C Journal of Cardiac Failure Vol. 16 No. 6 2010

29. ACE Inhibitors in Heart Failure:From Asymptomatic LVD to Severe HF SOLVD Prevention (Asymptomatic LVD) • 20% death or HF hosp. • 29% death or new HF CONSENSUS (Severe Heart Failure) • 40% mortality at 6 mos. • 31% mortality at 1 year • 27% mortality at end of study SOLVD Treatment (Chronic Heart Failure) mortality 16% SOLVD Investigators. N Engl J Med 1992;327:685-91 SOLVD Investigators. N Engl J Med 1991;325:293-302 CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35

30. ACE Inhibitors Used in Clinical Trials *No mortality difference between high and low dose groups, but 12% lower risk of death or hospitalization in high dose group vs. low dose group.

31. HFSA 2010 Practice Guideline (7.2)Pharmacologic Therapy:Substitutes for ACEI • It is recommended that other therapy be substituted for ACE inhibitors in the following circumstances: • In patients who cannot tolerate ACE inhibitors due to cough, ARBs are recommended. Strength of Evidence= A • The combination of hydralazine and an oral nitrate may be considered in such patients not tolerating ARBs.Strength of Evidence = C • Patients intolerant to ACE inhibitors from hyperkalemia or renal insufficiency are likely to experience the same side effects with ARBs. In these cases, the combination of hydralazine and an oral nitrate should be considered. Strength of Evidence = C Journal of Cardiac Failure Vol. 16 No. 6 2010

32. HFSA 2010 Practice Guideline (7.6, 7.7)Pharmacologic Therapy: Beta Blockers • Beta blockers shown to be effective in clinical trials are recommended for symptomatic and asymptomatic patients with an LVEF ≤ 40%. Strength of Evidence = A • Beta blockers are recommended as routine therapy for asymptomatic patients with an LVEF ≤ 40%. • Post MIStrength of Evidence = B • Non Post-MIStrength of Evidence = C Journal of Cardiac Failure Vol. 16 No. 6 2010

33. Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD 1Colucci WS et al. Circulation 1196;94:2800-6. 2CIBIS II Investigators. Lancet 1999;353:9-13. 3MERIT-HF Study Group. Lancet 1999;353:2001-7. 4Packer M et al. N Engl J Med 2001;344 1651-8. 5The CAPRICORN Investigators. Lancet 2001;357:1385-90.

34. HFSA 2010 Practice Guideline (7.8)Pharmacologic Therapy: Beta Blockers • Beta blocker therapy is recommended for patients with a recent decompensation of HF after optimization of volume status and successful discontinuation of IV diuretics and vasoactive agents. • Whenever possible, beta blocker therapy should be initiated in the hospital at a low dose prior to discharge of stable patients.Strength of Evidence = B Journal of Cardiac Failure Vol. 16 No. 6 2010

35. HFSA 2010 Practice Guideline (7.11)Pharmacologic Therapy: Beta Blockers • Continuation of beta blocker therapy is recommended in most patients experiencing a symptomatic exacerbation of HF during chronic maintenance treatment, unless they develop cardiogenic shock, refractory volume overload, or symptomatic bradycardia.Strength of Evidence = C • Temporary dose reduction may be considered • Avoid abrupt discontinuation • Reinstate or gradually increase prior to discharge • Titrate dose to previously tolerated dose as soon as possible Journal of Cardiac Failure Vol. 16 No. 6 2010

36. IMPACT-HF Primary End Point:Patients Receiving Beta Blocker at 60 Days Improvement 18% CarvedilolPredischarge Initiation (n=185) Physician Discretion Postdischarge Initiation* (n=178) Gattis WA et al. JACC 2004;43:1534-41

37. HFSA 2010 Practice Guideline (7.9)Pharmacologic Therapy: Beta Blockers CONCOMITANT DISEASE • Beta blocker therapy is recommended in the great majority of patients with HF and reduced LVEF—even if there is concomitant diabetes, chronic obstructive lung disease or peripheral vascular disease. • Usewith caution in patients with: • Diabetes with recurrent hypoglycemia • Asthma or resting limb ischemia. • Use with considerable caution in patients with marked bradycardia (<55 bpm) or marked hypotension (SBP < 80 mmHg). • Not recommended in patients with asthma with active bronchospasm. Strength of Evidence = C Journal of Cardiac Failure Vol. 16 No. 6 2010

38. 0.5 1.5 2.0 0 1.0 Diabetes and the Use of Beta Blockers for HF: Relative Risk for Mortality and Hospitalization for Heart Failure COPERNICUS (carvedilol)1 With diabetes Without diabetes MERIT-HF (ER metoprolol succinate)2 With diabetes Without diabetes Mohacsi. Circulation. 2001;104(17):abstr 3551. Hjalmarson. JAMA. 2000;283(10):1295.

39. HFSA 2010 Practice Guideline (11.8, 15.2)Pharmacologic Therapy: Beta Blockers PRESERVED LVEF • Beta blocker treatment is recommended in patients with HF and preserved LVEF who have: • Prior MIStrength of Evidence = A • Hypertension Strength of Evidence = B • Atrial fib. requiring control of ventricular rateStrength of Evidence = B THE ELDERLY • Beta-blocker and ACE inhibitor therapy is recommended as standard therapy in all elderly patients with HF due to LV systolic dysfunction.Strength of Evidence = B • In the absence of contraindications, these therapies are also recommended in the very elderly (age > 80 years). Strength of Evidence = C Journal of Cardiac Failure Vol. 16 No. 6 2010

40. HFSA 2010 Practice GuidelinePharmacologic Therapy: Beta Blocker Overview* Journal of Cardiac Failure Vol. 16 No. 6 2010

41. Beta Blockers Used in Clinical Trials

42. HFSA 2010 Practice Guideline (7.3)Pharmacologic Therapy: Angiotensin Receptor Blockers • ARBs are recommended for routine administration to symptomatic and asymptomatic patients with an LVEF ≤ 40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insufficiency. • Strength of Evidence = A Journal of Cardiac Failure Vol. 16 No. 6 2010

43. Val-HeFT ARBS in Patients Not Taking ACE Inhibitors: Val-HeFT & CHARM-Alternative CHARM-Alternative Placebo Valsartan Survival % CV Death or HF Hosp % Placebo Candesartan p = 0.017 HR 0.77, p = 0.0004 Months Months Maggioni AP et al. JACC 2002;40:1422-4 Granger CB et al. Lancet 2003;362:772-6

44. Angiotensin Receptor Blockers Used in Clinical Trials

45. HFSA 2010 Practice Guideline (7.14-7.15)Pharmacologic Therapy: Aldosterone Antagonists • An aldosterone antagonist is recommended for patients on standard therapy, including diuretics, who have: • NYHA class IV HF (or class III, previously class IV) HF from reduced LVEF (≤ 35%) • One should be considered in patients post-MI with clinical HF or diabetes and an LVEF < 40% who are on standard therapy, including an ACE inhibitor (or ARB) and a beta blocker. Strength of Evidence = A Journal of Cardiac Failure Vol. 16 No. 6 2010

46. RALES (Advanced HF) Aldosterone Antagonists in HF EPHESUS (Post-MI) Eplerenone Probability of Survival Spironolactone Placebo Placebo RR = 0.70 P < 0.001 RR = 0.85 P < 0.008 Months Pitt B. N Engl J Med 1999;341:709-17 Pitt B. N Engl J Med 2003;348:1309-21

47. HFSA 2010 Practice Guideline (7.16-7.18) Aldosterone Antagonists and Renal Function • Aldosterone antagonists are not recommended when: • Creatinine > 2.5mg/dL (or clearance < 30 mL/min) • Serum potassium> 5.0 mmol/L • Therapy includes other potassium-sparing diuretics Strength of Evidence = A • It is recommended that potassium be measured at baseline, then 1 week, 1 month, and every 3 months Strength of Evidence = A • Supplemental potassium is not recommended unless potassium is < 4.0 mmol/L Strength of Evidence = A Journal of Cardiac Failure Vol. 16 No. 6 2010

48. EMPHASIS-HF • Trial of 2737 patients with NYHA class 2 heart failure and an ejection fraction of no more than 35%. • Patients were randomized to eplerenone (up to 50mg daily) or placebo in addition to recommended therapy. • Measured outcomes included: cardiovascular death/heart-failure hospitalization, cardiovascular death, heart-failure hospitalization, and hospitalization for hyperkalemia. • Trial was stopped early at 21months.

49. EMPHASIS-HF • EMPHASIS-HF Major results • Results in a 37% reduction in the primary end point of the composite of death from cardiovascular causes or hospitalization for heart failure!! • Hyperkalemia occurring in 11.8% of eplerenone patients vs 7.2% of those in placebo group!!!

50. HFSA 2010 Practice Guideline (7.19)Pharmacologic Therapy:Hydralazine and Oral Nitrates • A combination of hydralazine and isosorbidedinitrateis recommended as part of standard therapy, in addition to beta-blockers and ACE-inhibitors, for African Americans with HF and reduced LVEF: • NYHA III or IV HF Strength of Evidence = A • NYHA II HF Strength of Evidence = B Journal of Cardiac Failure Vol. 16 No. 6 2010