Critical Challenges of Acute Heart Failure

Transcription

1 Critical Challenges of Acute Heart Failure Jonathan Howlett, MD, FRCPC, FACC Libin Cardiovascular Institute and University of Calgary President, Canadian Heart Failure Society Presenter Disclosure Faculty/Presenter: Dr. Jonathan Howlett Relationships with commercial interests: Grants/research support: Speaker s bureau/honoraria: Consulting fees: Other: Servier, Medtronic, Bayer AstraZeneca, Novartis, Merck, Servier, Pfizer, Medtronic, Abbott, Bayer n/a I ALWAYS SEEM TO DISCUSS OFF LABEL USE OF MEDICATIONS AND EVEN THOUGH I HAVE NO PLANS TO DO SO TODAY, I SOMETIMES DO IT ANYWAY!!!! 1

2 Case study LG is an 76 year old man with a history of Type 2 DM, hypertension, and remote MI He was hospitalized 2 years ago with mild HF/NSTEMI At the time of hospitalization an echo revealed an EF of 34% Has done well since In your office Physical BP 128/78 Pulse edema Laterally displaced + enlarge apex Basil crackles 5 cm ASA Wt gain since last seen (6 weeks ago) 5.3 kg 2

3 Cardiac Meds + Labs (6 weeks ago) CBC N Creat egfr = 48 Lytes N (K = 4.2) Furosemide 60 mg OD Spironolactone 50 mg OD ECASA 81 mg OD Ramipril 5 mg bid Metoprolol 50 mg bid Questions What is your diagnostic impression of this patient? What further investigations would you order? What therapeutic changes would you consider? 3

4 Challenges with HF Care in Canada While HF incidence and death are static, overall prevalence is increasing Risk/Mismatch for patient care is endemic Differential HF Clinic access for patients remains a problem Rural HF care lacks support Crude CHF Deaths in Canada Mortality for CHF J-81 J-83 J-85 J-87 J-89 J-91 J-93 J-95 J-97 J-99 J-01 J-03 J-05 Year Campbell NR, Can J Cardiol. 2006;22:

5 Table 1. Projections of the US Population With HF From 2010 to 2030 for Different Age Groups Year All y y y 80 y ,813, ,578 1,907,141 2,192,233 1,317, ,190, ,926 1,949,669 2,483,853 1,354, ,859, ,600 1,974,585 3,004,002 1,463, ,644, ,635 1,696,852 3,526,347 1,713, ,489, ,275 2,000,896 3,857,729 2,180,528 HF indicated heart failure Cost ($ Billions) Direct Indirect Circ Heart Fail. 2013;6: Readmission Predictors Renal disease was associated with 7-day all-cause readmissions (adjusted odds ratio [aor] 1.28, 95% confidence interval [CI] ) Cancer, pulmonary, liver, and renal disease were assocaited with 30-day all-cause readmissions Discharge with homecare services was a risk factor for readmission 7 days (aor 1.26, 95% CI ) 30 days (aor 1.23, 95% CI ) Discharge from a hospital with HF services associated with lower readmission 7 days (aor 0.65, 95% CI ) 30 days (aor 0.71, 95% CI ) Eastwood et al CJC,

6 What do the Guidelines Say? Disease Management Programs Recommendations (cont d) Patients with recurrent HF hospitalization should be referred to a DMP by family physicians, emergency room physicians, internists or cardiologists for follow-up within four weeks of hospital or emergency department discharge, or sooner where feasible (Class I, Level A) 6

7 Follow-up Cardiovascular Care Importance of Follow-up Care: A study of 3,136 patients in Alberta with Heart Failure found those who received regular cardiovascular follow-up visits with a family physician had better outcomes Kaplan Meier Survival Curves For Care Received, by Ambulatory Specialty 1.0 Cumulative Survival Log-rank = p < Days of Follow-up Combined care (both specialist and family physician) Care by family physician only No follow-up care Ezekowitz JA, et al. Impact of specialist follow-up in outpatients with congestive heart failure. CMAJ 2005;172: For Heart Failure Clinic/Specialist Care To Be Incorporated Collaboratively with Primary Care Recommended Initial Referral Wait Time and Follow up Frequency See within: Follow-up: 12 wks (ideally within 6 wks) Routine, Elective Referral 4 wks (ideally within 2 wks) Semi- Urgent, Intermediate Risk Less than 2 weeks Urgent See within 24 hrs Emergent Heart Failure Care Every 1-4 wks Every 1-6 mo. Every 6-12 mo High Risk Individual Intermediate Risk Individual Low Risk Individual Make inactive or consider for discharge from HF clinic if 2 of the following are present: Stable NYHA I or II for 6-12 months ON optimal therapies Reversible Causes of HF fully controlled Having access to General Practitioner with expertise in management of HF Stable adherence to optimal HF Therapy No hospitalizations for >1 year LVEF >35% (consistently shown if more than one recent EF measurement) Primary Care provider has access to urgent specialist reassessment 7

8 Predictors of at Least One LV EF Measurement Within 1 Year of Hospital Discharge in Alberta Female vs. Male Age (every 10 years increase) Charlson index (1 point increase) Cardiology services Present vs. Absent Metropolitan vs. Urban Metropolitan vs. Rural Urban vs. Rural Odds Ratio Howlett et al, Vascular 2013 CCS Guidelines Non-Pharmacological Management: What Should HCPs Look For and Talk About? Talk to patients about their priorities Identify specific targets for therapy Look for, and treat, depression Discuss advance directives, living wills and substitute decisionmakers Follow patients closely and systematically Educate about early warning signs of decompensation and how to respond Discuss salt and fluid intake Use daily morning weights with a diary and tailored prn diuretic dosing Measure supine and erect BP Follow creatinine and K+ closely Eliminate harmful drugs Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):

9 RW9 Team Approaches and In-Person Communication Reduce HF Readmissions Sochalski J, et al. Health Aff (Millwood) Jan-Feb;28(1):

10 Slide 17 RW9 Omit Rick Ward, 10/18/2015

11 Risk Treatment Mismatch in the Pharmacotherapy of Heart Failure Low risk Moderate risk High risk 70 Percentage ACE ACE/ARB Beta Blockers Lee et al. EFFECT Study JAMA 2005;294:

12 Access to HF Clinics One year follow up > 2000 hosp, Canadian metro hospitals 13% seen in DM or HF Clinic Cohort seen were younger, lower risk, more likely to see Cardiology and visit other disease clinics THIS = RISK TREATMENT MISMATCH Gravely S, Can J Cardiol 2012;28: Proportion of CHF Patients Returning to Outpatient Clinic/Program 365 Days Post Discharge by Program Type ACCS Outpatient Program/Clinic 11

13 Canadian CHF: MD Ratios 29,367 GPs in Canada 19,992 specialists, 2,344 Internal Medicine 862 Cardiologists 350,000 patients with CHF 12/FD 149/IM 406/Card CHF Care must be by FMD!!! 12

14 Importance of dose to achieve maximum impact- ATLAS Risk of Hyperkalemia Does Not Vanish, Even After >1 Year Patients with K >6.0 at any time, % Eplerenone Placebo Days to 1 st occurrence of K >6.0 Adapted from Pitt B et al. Circulation 2008; 118(16):

15 Model for Future Disease Management of HF FROM THIS..TO THIS!! Heart Failure Clinic Heart Failure Clinic Patient with Heart Failure Other Care Provider Patient with Heart Failure Primary Care Provider Primary Care Provider Characteristics of the Current vs. Desired HF Clinic Characteristic Current HF clinic Desired HF clinic Personnel HF specialists, nurses, clerical staff, occasionally dieticians, physiotherapists, social workers, pharmacists Same as current as resources allow Patient composition Care setting Clinic procedures Visit composition HF, heart failure Ad hoc referrals, various sources, generally lower risk than unselected HF patients Stand-alone HF clinic with variable primary care links Highly variable between clinics, usually unwritten 80-90% return, 10-20% new. Follows <15% of HF population All new HF patients with triage of low-risk patients back to primary care. Higher-risk patients than unselected HF population Providing links to primary HF care, easy access for advice/follow-up, support for capacity build-in primary HF care. Primary HF care is standardized and described Clearly defined procedures encompassing provision of self-care skills, medication reconciliation, and teaching, HF education and warning signs, volume assessment, and standardized care protocols 40% return, 60% new or reasessments, with potential coverage of 50% of HF population 14

16 What Do We Need to Make This Sea Change? Involve primary care in HF care by supporting it Mentoring actively MDs and Nurses Ongoing communications Tools for use in daily practice Realign referral patterns Allow for primary care for non-high risk Support and Monitor Key Quality Indicators 15

17 RW5 Systolic vs Diastolic HF: Different Diseases with the Same Prognosis? Survival (%) Preserved ejection fraction Reduced ejection fraction HTN DM Preserved EF or Diast HF Days Adjusted Survival Curves for Patients with Heart Failure with Reduced or Preserved Ejection Fraction over the Year after the First Hospital Admission. Reduced EF or Syst HF Bhatia S, Liu P, et al., N Engl J Med 2006; 55:

18 Slide 32 RW5 A further explanation of Diastolic verus Systolic HF may be needed for the Primary Care audience. The flip side is 'does this impact treatment'? If not, maybe not necessary for mentioning to a Primary Care audience. Rick Ward, 10/18/2015

19 Therapeutic Approach to Patients with Heart Failure and Reduced Ejection Fraction Helpful links Link to CCS Heart Failure medication titration app (MED-hf) and HF Guidelines app (iccs): Link to Heart Failure Pocket Document: Link to Heart Failure Guidelines Slide Decks: 17

20 RW6 Decline in Systolic Function Leads to Activation of Three Major Neurohormonal Systems Sympathetic nervous system Natriuretic peptide system NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy HF SYMPTOMS & PROGRESSION Epinephrine Norepinephrine Renin angiotensin aldosterone system Ang II α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility AT 1 R Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis Ang=angiotensin; AT 1R=angiotensin II type 1 receptor; HF=heart failure; NPs=natriuretic peptides; NPRs=natriuretic peptide receptors; RAAS=renin-angiotensin-aldosterone system Levin et al. N Engl J Med 1998;339:321 8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42; Kemp & Conte. Cardiovascular Pathology 2012; ; Schrier & Abraham. N Engl J Med 2009;341: RW7 Sustained Activation of the RAAS Has a Detrimental Effect in HF Cardiac dysfunction leads to RAAS activation sustained activation puts further strain on the weakened heart, creating a vicious cycle RAAS suppression as an effective strategy in treating HF 1 Hypertrophy Fibrosis Cardiac remodeling Myocyte necrosis Sympathetic tone Heart rate Contractility ACE Sodium and water retention Blood volume ACEIs ARBs MRAs Angiotensinogen Direct renin inhibitors* Ang I Ang II Adrenal gland Aldosterone Renin Vasoconstriction Hypertrophy Blood pressure ADH secretion Pituitary gland Water absorption Blood volume *Studies ongoing; not approved for treatment of HF ACE=angiotensin-converting enzyme; ACEI=angiotensin-converting-enzyme inhibitor; ADH=antidiuretic hormone; ARB=angiotensin receptor blocker; Ang=angiotensin; HF=heart failure; MRA=mineralocorticoid receptor antagonist; RAAS=reninangiotensin-aldosterone system Zaman et al. Nat Rev Drug Discov 2002;1:621 36; Schrier, Abraham. N Engl J Med 1999;341:577 85; Brewster et al. Am J Med Sci 2003;326:15 24; Schmeider. Am J Hypertens 2005;18: ; McMurray et al. Eur Heart J 2012;33:

21 Slide 35 RW6 Add overlay of Rx's 1. BB over sympathetic 2. ACE or ARB over RAAS 3. NEP inhibitor over NPS Rick Ward, 11/23/2015 Slide 36 RW7 great slide. For completeness, would build similar slide for Sympathetic Response Rick Ward, 10/18/2015

22 RW8 NEP inhibition must be accompanied by simultaneous RAAS blockade NEP metabolizes Ang I and Ang II via several pathways 1,2 Inhibition of NEP alone is insufficient as it associated with an increase in Ang II levels, counteracting the potential benefits of NEP inhibition 2 NEP inhibition must be accompanied by simultaneous RAAS blockade (e.g. AT 1 receptor blockade) 2 Angiotensinogen Renin Ang I ACE Ang II NEP NEP Ang-(1 7) Inactive fragments AT 1 receptor Signaling cascade Biological actions Hypertrophy Fibrosis Vasoconstriction Hypertrophy Na + /H 2 O retention Aldosterone release Norepinephrine release Sympathetic tone ACE=angiotensin converting enzyme; AT 1 = angiotensin II type 1; Ang=angiotensin; NEP=neprilysin; RAAS=renin angiotensin aldosterone system 1. Von Lueder et al. Circ Heart Fail 2013;6: ; 2. Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131 9 Summery Decline in systolic function activates Neurohormonal System Effect on HF Target Medication Classes Effect Sympathetic Worsens Beta blockers Reduces sympathetic overdrive RAAS Worsens ACE-I Blocks RAAS ARB Naturietic Peptide System Improves Neprilysin Inhibitor Augments NPS Note NEP inhibitor must be combined with RAAS inhibition - RAAS inhibition must be done via ARB (increase angioedema if NEP inhibitor + ACE) 19

23 Slide 37 RW8 Would simplify this slide to highlight the key message: NEP inhibition must be accompanied by RAAS inhibition. If NEP inhibition alone - RAAS with compensate and upregulate, negating clinical benefits. Rick Ward, 10/18/2015

24 Primary Endpoint: Death from CV Causes or First Hospitalization for HF Cumulative probability Enalapril LCZ696 NNT to prevent one primary event: 21 HR: 20% difference favoring LCZ696 Hazard ratio = 0.80 (95% CI: ) p< No at risk Days since randomization LCZ Enalapril *The numbers of patients who would need to have been treated (NNT) to prevent one primary event was evaluated over the duration of the trial McMurray et al. N Engl J Med 2014;371 (11): Angiotensin Neprilysin Inhibition With LCZ696 Doubles Effect on Cardiovascular Death of Current Inhibitors of the Renin-Angiotensin System 14MDL281E 20

25 Adverse Events Leading to Permanent Study Drug Discontinuation Fewer patients in the LCZ696 group than in the enalapril group discontinued study drug due to an adverse event (10.7 vs 12.3%; p=0.03) Patients who discontinued study drug (%) 15 p= Any adverse event LCZ696 (n=4,187) Enalapril (n=4,212) p=0.38 p= p= Hypotension Renal impairment Hyperkalemia McMurray et al. N Engl J Med 2014;371 (11): Yes but. Need to stop ACE x 36 hours (risk angioedema) Best results if switched from maximum dose ACE Need to monitor BP and creatinine (LCZ can lower BP/raise creatinine) 21

26 Key HF themes 1. Incidence is increasing 2. Chronic, deteriorating disease with significant morbidity and heath care costs 3. Best managed by primary care in partnership with cardiology Please visit our website for more information and download our CCS guideline Apps 22