Disclosures This speaker has indicated there are no relevant financial relationships to be disclosed.
And the Beat Goes On: New Medications for Heart Failure Alison M. Walton, PharmD, BCPS
The Case of the Swollen Snowbird 74 year old African American male presents to emergency department with angioedema. Accompanied by spouse who lives with patient at home. States returned to Indianapolis this past week after a recent hospitalization during winter stay in Florida. PMH: HFrEF (ACCF/AHA Stage C, NYHA FC III), CAD with history of MI 3 years ago, HTN, Osteoarthritis Vitals: BP 110/74mmHg, HR 64bpm;Ht 6ft, Wgt 215lb Medications: unknown, son sets-up pillbox Pertinent labs: scr 1.2, K 4.5 Echo: LVH, estimated EF = 30% 3
Medication Review Pharmacist contacts patient s son for medication review by phone. Son states sets-up pillbox for a month in advance then his mom helps remind dad to take his medications. Reported Medications Carvedilol 12.5mg po twice daily Lisinopril 10mg po daily Spironolactone 25mg po daily Atorvastatin 80mg po daily Aspirin 81mg po daily Ibuprofen 200mg po twice daily for knee pain Multivitamin once daily 4
Medication Review continued Receive discharge summary from recent hospitalization. Patient s wife remembers 2 new medications started in hospital and she added to pillbox. She tells you one was very expensive but knew it was important for him to take. Medications per Discharge Summary Carvedilol 25mg po twice daily Sacubitril/Valsartan 49/51mg po twice daily Spironolactone 25mg po daily Atorvastatin 80mg po daily Furosemide 40mg po twice daily Aspirin 81mg po daily Multivitamin once daily 5
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New Medications for Heart Failure Learning Objective: Describe new medications for heart failure (HF) and apply this knowledge to care for older adults. 7
Ivabradine (Corlanor ) New Drug Class, Approved April 2015 Hyperpolarization-activated cyclic nucleotide-gated channel blocker (I f inhibitor); Sinoatrial (SA) node HR lowering occurs without negative inotropic or vascular constriction effects Role in Therapy: SHIFT Trial Reduce risk of HF hospitalization FDA Indication Patients with stable, symptomatic chronic heart failure with EF < 35%, who are in sinus rhythm with resting HR > 70bpm and either on maximum tolerated doses of beta-blockers or contraindication to beta-blocker use 8 Lancet. 2010;367(9744):875-85.
Ivabradine Dosing 9 Initial dose 5mg by mouth twice daily with meals Decrease initial dose to 2.5mg twice daily if history conduction defects or may experience hemodynamic compromise due to bradycardia After 2 weeks, adjust dose to achieve resting heart rate 50-60 bpm; Maximum dose 7.5mg twice daily Heart Rate (resting) Dosage Titration > 60 bpm Increase dose by 2.5mg twice daily up to maximum dose of 7.5mg twice daily 50-60 bpm Maintain dose < 50 bpm or signs/symptoms of bradycardia Decrease dose by 2.5mg twice daily; Discontinue if current dose 2.5mg twice daily
Ivabradine Warnings Contraindications Acute decompensated HF BP < 90/50mmHg; Resting HR < 60bpm Sick sinus syndrome; Heart block; Pacemaker dependence Severe hepatic impairment Warnings/Precautions Fetal toxicity Atrial fibrillation Bradycardia and conduction disorders Caution CrCl <15mL/min (not studied) 10
Ivabradine Monitoring Drug Interactions Avoid strong CYP3A4 inhibitors/inducers Avoid use with verapamil and diltiazem Adverse Effects Bradycardia (6-10%) Hypertension (9%) Atrial fibrillation (5-8%) Temporary vision disturbance (3%) Monitoring Parameters Heart rate and blood pressure Cardiac rhythm 11
Ivabradine in Older Adult Efficacy and safety comparable across the age spectrum Analysis of SHIFT Trial (n=6505, mean age 60.4 yrs +/- 11.4 yrs) with redistribution of ages into 4 groups: <53 years (n=1522), 53 - <60 years (n=1521), 60 - <69 years (n=1750), and >69 years (n=1712; 47% >75 yr) Efficacy: HR reduction (11bpm) similar with age groups Reduction in primary endpoint for all age groups Safety Adverse effects (bradycardia and visual changes) increased with age, but no substantial differences between ivabradine and placebo with age groups Atrial fibrillation >69 yr (11%) vs <53 yr (5%) 12 Eur J Heart Fail. 2013;15(11):1296-1303.
Sacubitril/Valsartan (Entresto ) New Drug Class, Approved July 2015 Angiotensin receptor-neprilysin inhibitor (ARNI) Effects on renin-angiotensin system, natriuretic-peptide system, and bradykinin Role in Therapy: PARADIGM-HF Trial Reduce cardiovascular death and HF hospitalization FDA Indication Patients with chronic heart failure (NYHA FC II-IV) and reduced EF, administered in conjunction with other HF therapies in place of ACE Inhibitor or other ARB 13 N Engl J Med 2014;371:993-1004.
Sacubitril/Valsartan Dosing Fixed combination product Starting dose 49/51mg by mouth twice daily Double the dose every 2-4 weeks to achieve target dose of 97/103mg twice daily Administer with or without food Use reduced starting dose of 24/26mg twice daily Not currently taking ACE Inhibitor/ARB or on low doses (enalapril total daily dose <10mg; lisinopril <10mg; valsartan total daily dose <160mg, losartan <50mg) Severe renal impairment (egfr <30mL/min) or moderate hepatic impairment 14
Sacubitril/Valsartan Warnings Contraindications History of angioedema with ACE Inhibitor or ARB Concomitant use or use within 36 hours of ACE Inhibitor: Washout period of 36 hours required when switching from ACE Inhibitor due to angioedema risk Concomitant use with aliskiren in patients with diabetes Warnings/Precautions Fetal toxicity Angioedema Hypotension: Avoid in patients with SBP < 100mmHg Impaired renal function; Hyperkalemia 15
Sacubitril/Valsartan Monitoring Adverse Effects Angioedema (Black patients 2%; Others <1%) Hypotension (18%); Orthostatic hypotension (2%) Impaired renal function (1-16%) Hyperkalemia (4-16%) Dizziness (6%); Falling (2%)??? Risk of dementia Monitoring Parameters Blood pressure Renal function and potassium 16
Sacubitril/Valsartan in Older Adult Efficacy and safety comparable across the age spectrum Analysis of PARADIGM-HF (n=8399, mean age 64 years with range 18-96 years) with redistribution of ages into 4 groups: <53 years (n=1624), 55-64 years (n=2655), 65-74 years (n=2557), and >75 years (n=1563; 7% >80 yrs) Efficacy Reduction in primary endpoint similar for all age groups Safety Adverse effects more common with increasing age Symptomatic hypotension >75 yrs (17.7%) vs <55 yrs (11.5%), but few discontinued medication 17 Eur Heart J. 2015:36;2576-2584.
Role of Heart Failure Medications REDUCE MORTALITY ACE Inhibitor ARB Beta-blocker Aldosterone Antagonist Nitrate/Hydralazine Sacubitril/Valsartan NO MORTALITY BENEFIT Diuretics Digoxin Ivabradine 18
Patient Case Medication Mistake Comprehensive Medication List Carvedilol 12.5mg po twice daily Lisinopril 10mg po daily Sacubitril/Valsartan 49/51mg po twice daily Spironolactone 25mg po daily Atorvastatin 80mg po daily Aspirin 81mg po daily Furosemide 40mg po twice daily Ibuprofen 200mg po twice daily for knee pain Multivitamin once daily 19
And the Beat Goes On: New Medications for Heart Failure Alison M. Walton, PharmD, BCPS amwalton@stvincent.org
References Jhund PS, Fu M, Bayram E, et al. Efficacy and safety of LCZ696 (sacubitril-valsartan) acording to age: insights from PARADIGM-HF. Eur Heart J. 2015:36;2576-2584. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004. PL Detail-Document, Heart Failure Treatment at a Glance. Pharmacist s Letter/Prescribers Letter. November 2013 (Modified August 2015). PL Detail-Document, Target Doses for Meds with Systolic Heart Failure. Pharmacist s Letter/Prescribers Letter. November 2013 (Modified January 2016). Product Information for Corlanor. Amgen, Inc. Thousand Oaks, CA 91320. April 2015. Product Information for Entresto. Novartis Pharmaceuticals. East Handover, NJ 07936. August 2015. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure(shift): a randomised placebo-controlled study. Lancet. 2010;367(9744):875-85. Tavazzi L, Swedberg K, Komajda M. Efficacy of ivabradine in chronic heart failure across the age spectrum. Eur J Heart Fail. 2013;15(11):1296-1303. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;128:e240-e327. 21