CLASS I GUIDELINE RECOMMENDED 3 LEVEL OF EVIDENCE B-R ACC/AHA/HFSA ENTRESTO ® demonstrated reduced risk of HF hospitalization and death vs enalapril in the largest trial ever conducted in HF 4,5 * † : CV DEATH OR HF HOSPITALIZATION AS FIRST EVENT 4 (primary end point) ( P <0.0001; HR [95% CI]: 0.80 [0.73, 0.87]) 20 4.7 % ARR RRR % ALL-CAUSE MORTALITY 4‡ ( P =0.0009; HR [95% CI]: 0.84 [0.76, 0.93]) 16 % % ARR 2.8 RRR • Reduced the relative risk of CV death by 20% vs enalapril (3.2% ARR) 4†§ll • 5HGXFHGWKHUHODWLYHULVNRIÀ UVW+)KRVSLWDOL]DWLRQE\ 21% vs enalapril (2.8% ARR) 4† When you see symptoms, there’s risk, so it’s time for ENTRESTO . IMPORTANT SAFETY INFORMATION, CONT’D Impaired Renal Function, cont’d: In patients who are elderly, volume-depleted For more information, visit EntrestoHCP.com (including those on diuretic therapy), or with compromised renal function, concomitant XVH RI QRQ VWHURLGDO DQWL LQÁ DPPDWRU\ GUXJV �b;16$,'V�c;�f; LQFOXGLQJ &2;  LQKLELWRUV�f; = American College of Cardiology; AHA = American Heart Association; HFSA = Heart Failure Society with ENTRESTO may result in worsening of renal function, including possible acute ACC of America; B-R = Class of Recommendation B, randomized trial; CV = cardiovascular; RRR = relative risk renal failure. These effects are usually reversible. Monitor renal function periodically. UHGXFWLRQe; $55 DEVROXWH ULVN UHGXFWLRQe; +5 KD]DUG UDWLRe; &, FRQÀGHQFH LQWHUYDOe; 1<+$ 1HZ <RUN Hyperkalemia: Hyperkalemia may occur with ENTRESTO. Monitor serum potassium Heart Association; HF r EF = heart failure with reduced ejection fraction; ACEi = angiotensin-converting enzyme periodically and treat appropriately, especially in patients with risk factors for inhibitor; ARB = angiotensin II receptor blocker. PARADIGM-HF was a multinational, randomized, double-blind trial comparing ENTRESTO to enalapril in symptomatic hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a * (NYHA Class II-IV) adult HF r ()SDWLHQWV�b;OHIWYHQWULFXODUHMHFWLRQIUDFWLRQ �c;$IWHUGLVFRQWLQXLQJWKHLUH[LVWLQJ high potassium diet. Dosage reduction or interruption of ENTRESTO may be required. ACEi or ARB therapy, patients entered sequential single-blind run-in periods during which they received enalapril Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, 10 mg twice daily, followed by ENTRESTO 100 mg (49/51 mg) twice daily, increasing to 200 mg (97/103 mg) twice daily. were then randomized to receive either ENTRESTO 200 mg (97/103 mg) (n=4209) twice daily or enalapril amiloride), potassium supplements, or salt substitutes containing potassium may lead Patients 10 mg (n=4233) twice daily. The median follow-up duration was 27 months, and patients were treated for up to 4.3 years. † to increases in serum potassium. Analyses of the components of the primary composite end point were not prospectively planned to be adjusted for multiplicity. ARBs: Avoid use of ENTRESTO with an ARB, because ENTRESTO contains the ‡ (175(672LPSURYHGRYHUDOOVXUYLYDO7KLVÀ QGLQJZDVGULYHQHQWLUHO\E\DORZHULQFLGHQFHRI&9PRUWDOLW\RQ(175(672 § angiotensin II receptor blocker valsartan. Overall, sudden death accounted for 45% of CV deaths, followed by pump failure, which accounted for 26%. Lithium: Increases in serum lithium concentrations and lithium toxicity have been ll Includes subjects who had HF hospitalization prior to death. reported during concomitant administration of lithium with angiotensin II receptor References: 1. Ekman L, Cleland JGF, Swedberg K, Charlesworth A, Metra M, Poole-Wilson PA. Symptoms in patients with heart failure are prognostic predictors: insights from COMET. J Card Fail . 2005; 11(4):288-292. 2. Wong M, antagonists. Monitor serum lithium levels during concomitant use with ENTRESTO. Staszewsky L, Carretta E, et al. Signs and symptoms in chronic heart failure: relevance of clinical trial results to point Common Adverse Events: In a clinical trial, the most commonly observed adverse of care—data from Val-HeFT. Eur J Heart Fail . 2006;8(5):502-508. 3. Yancy CW, Jessup M, Bozkurt B, et al. 2016 events with ENTRESTO vs enalapril, occurring at a frequency of at least 5% in either ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA for the management of heart failure: a report of the American College of Cardiology Foundation/American group, were hypotension (18%, 12%), hyperkalemia (12%, 14%), cough (9%, 13%) guideline Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America [published dizziness (6%, 5%) and renal failure/acute renal failure (5%, 5%). online ahead of print May 20, 2016]. Circulation . doi: 10.1161/CIR.0000000000000435. 4. ENTRESTO [prescribing Please see Brief Summary of Prescribing Information, including Boxed WARNING, on following pages. information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2015. 5. McMurray JJV, Packer M, Desai AS, et al. Baseline characteristics and treatment of patients in Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail . 2014;16(7):817-825.