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V) in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and Compliance with Guideline-Directed (GD) Concomitant Medical Therapy for Heart Failure
The 22nd Annual Scientific Meeting HFSA
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072 Initiation of Sacubitril/Valsartan Early after Heart Failure Decompensation Kathleen A. Packard, Daniel E. Hilleman; Creighton University, Omaha, NE Background: Sacubitril/Valsartan (S/V) is indicated in stable, symptomatic HFrEF as an alternate to an ACEI or ARB. Initiation of S/V requires planning and care coordination with relatively low rates of utilization despite a Class I-BR recommendation. Starting S/V early after a hospitalization for HF may increase utilization. Methods: A retrospective chart review of HF patients who were initiated on S/V either in-hospital or within 7 days after hospitalization for decompensated HF was conducted. Patients had to have all of the following at the time of S/V initiation: HFrEF with EF 40%; serum K+ 4.0 5.0; serum creatinine 1.5 mg/dl; and a systolic BP 110 mmHg. Clinical outcomes of the patients were evaluated and descriptive statistics were used to analyze the data. Results: A total of 27 patients who met the inclusion criteria were evaluated. S/V was initiated in-hospital in 8 patients and outpatient in 19 patients. Baseline characteristics were mean age 71 § 7 years, 74% men, 93% white, NYHA FC class III 85% and class IV 15%, and mean EF 29% § 4%. Twenty patients were on an ACEI and 7 were on an ARB. All patients were on a beta-blocker and 18 were on an aldosterone receptor antagonist. Twelve (44%) patients tolerated S/V at last follow-up (5 months). Fifteen (56%) patients discontinued S/V therapy during the first month of treatment. S/ V was discontinued for hypotension in 7 patients and hypotension with acute kidney injury (AKI) in 8 patients. AKI was most likely secondary to pre-renal azotemia with 6 of the 8 patients with BUN/creatinine ratios > 20:1. Hypotension and AKI resolved in all patients upon discontinuation of S/V. There were no significant differences between patients continuing versus patients discontinuing S/V other than location of S/V initiation. Only 2 of 8 (25%) patients initiated in hospital continued S/V therapy while 10 of 19 (53%) outpatients continued therapy. However, there was no difference in the number of days from hospitalization to start of S/V therapy between those tolerating (10.3 § 2.0 days) and not tolerating S/V therapy (9.7 § 1.9 days). Conclusions: Early initiation of S/V may lead to greater utilization of this Class I recommended therapy, but our data suggests early initiation after HF decompensation is not tolerated in a majority of HF patients. Hypotension and AKI are the primary reasons for intolerance.
073 Initiation of Sacubitril/Valsartan (S/V) in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and Compliance with Guideline-Directed (GD) Concomitant Medical Therapy for Heart Failure Chunlan Chang1, Xue Song2, Michelle Choi3, Carol Duffy1; 1Novartis, East Hanover, NJ; 2IBM Watson Health, Cambridge, MA; 3University of Maryland, Baltimore, MD Background: The 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure (HF) Treatment guides healthcare providers on treatment plans and discussions with patients with HFrEF. Data on concomitant GD medical therapy for HF pre and post S/V initiation in the real world is limited. Objective: To assess concomitant GD medical therapy for HF pre and post S/V initiation. Methods: All adult patients with 1 claim for S/V or angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) in 7/7/2015-5/31/2016 were identified from a large administrative claims database. Patients on S/V were assumed to have HFrEF based on its approved indication. Patients on ACEI/ARB had claims-based evidence of HFrEF. The index date was 1st claim for S/V (searched first) or ACEI/ARB. All patients had data for 24 months pre-index and 6 months post-index, unless inpatient death occurred. The uses of GD beta blockers (BB) and mineralocorticoid receptor antagonists (MRA) were assessed. Daily dose of the last fill of GD BB and MRA within 12-month pre S/ V initiation and up to 4 fills post S/V was classified into 4 levels: <25%, 2550%, 50-75% and >75% of GD target dose. McNemar’s tests were conducted on % of patients with GD medications pre- and post-index; Cochran-Armitage tests were for the trend of target dose levels for all patients. Results: A total of 956 patients had 1 claim for S/V (median age 64 years, 71% male) and 55,492 patients had 1 claim for ACEI/ARB (median age 70 years, 62% male). Compared to pre S/V initiation, fewer S/V patients had concomitant GD BB (post vs. pre: 84.1% vs 89.3%) or MRA (47.7% vs 52.1%) post S/V; both p<.001. In contrast, the ACEI/ARB cohort had no marked difference in post- vs pre-index use of GD BB (67.1% vs 68.5%) or MRA (21.5% vs 22.1%). In the S/V cohort, 50.8% of patients started S/V at 24/26 mg b.i.d., 35.7% at 49/51 mg b.i.d., and 11.5% at 97/103 mg b.i.d. During the median follow-up of 433 days, 36.8% of patients reached target maintenance dose of 97/103 mg b.i.d. Importantly, among patients who remained on GD BB or MRA post S/V, daily doses did not vary post vs pre S/ V initiation (all p>0.10). About 34-35% and >70% of patients received >75% of GD target daily dose for BB and MRA, respectively, across all fills (Figure 1). Conclusions: The majority of patients remained on GD BB or MRA with S/V; most continued at the same dose level of GD BB and MRA. Thus, in real-world practice, S/V is prescribed concomitantly with GD BB and MRA without the need for dose adjustment in the majority of cases.
074 An Analysis on Clinical Outcomes and Diuretic Requirements Following Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure with Reduced Ejection Fraction Natalie Pierson, Cheryl Abbas, Gordon Reeves; Thomas Jefferson University Hospital, Philadelphia, PA Background: A post-hoc analysis of the PARADIGM-HF clinical trial demonstrated treatment with sacubitril/valsartan resulted in a significant reduction in patients with worsening NYHA functional class, as compared to enalapril. Additional post-hoc analyses have revealed a reduction in intensification in outpatient diuretics, as well as a reduction in overall daily diuretic requirements, for patients treated with sacubitril/valsartan verses enalapril. Real world evidence is limited in analyzing patient experiences surrounding improvement in HF symptoms and diuretic usage. Methods: This analysis was a retrospective chart review of patients consecutively prescribed sacubitril/valsartan at the Jefferson Heart Institute from January 1, 2016 until January 31, 2017. Patient clinical outcomes and diuretic requirements were analyzed for 3 months following maintenance on any dose of sacubitril/valsartan for four weeks. Chart examinations reviewed documentation for improvements in heart failure (HF) symptoms, NYHA functional class, and LVEF, as well as changes in concomitant HF medications. Safety endpoints included symptomatic hypotension and an elevation in serum creatinine and/or potassium. Results: A total of 42 patients were included in the analysis. Thirty-six patients (85.7%) were titrated from their initial starting dose, although only 28 patients (66.7%) reached the targeted dose of 97/103mg twice daily. Fifty-seven percent of the patients (24/42) reported improvements in their HF-related symptoms, while 38.1% (16/42) of the patients demonstrated improvement NYHA functional classification. Thirty-six patients were concomitantly receiving loop diuretics during the initiation of sacubitril/valsartan, of whom 6 (16.7%) and 14 patients (38.9%) required discontinuation and dose reductions of loop diuretics, respectively. Twenty-two patients had a repeat ECHO after sacubitril/valsartan was initiated, fourteen of whom (63.6%) showed improvements in their LVEF. Two patients required discontinuation of therapy due to an adverse reaction; however, no other discontinuations were required from symptomatic hypotension, hyperkalemia or renal impairment. Sixteen patients (38%) experienced symptomatic hypotension, and 50% of those patients were not titrated to the target dose. Conclusion: Treatment with sacubitril/valsartan resulted in an improvement in patient-reported HF symptoms, NYHA functional class and LVEF. Although the majority of patients were maintained on diuretics post initiation of sacubitril/valsartan, daily dose reductions were observed. Patients did not require discontinuation of therapy as a result of symptomatic hypotension, hyperkalemia and/or renal impairment. Despite a small sample size, this retrospective analysis serves as an example of real world experience with initiating sacubitril/valsartan in patients with chronic HFrEF.
075 AG10, A Novel, Potent and Selective Transthyretin Stabilizer, is Well Tolerated at Doses Resulting in Target Therapeutic Blood Levels, and Demonstrates Clinical Proof-of-Concept in Healthy Volunteers Jennifer L. Hellawell1, Satish Rao1, Terry O’Reilly2, Rick Lumpkin1, Jesper Jernelius1, Daniel Gretler1, Uma Sinha1, Jonathan C. Fox1; 1Eidos Therapeutics, Inc., San Francisco, CA; 2Celerion, Inc., Tempe, AZ Introduction: AG10 is a novel, potent and selective oral transthyretin (TTR) stabilizer under clinical development to treat TTR amyloidosis (ATTR). Both mutant and
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072 Initiation of Sacubitril/Valsartan Early after Heart Failure Decompensation Kathleen A. Packard, Daniel E. Hilleman; Creighton University, Omaha, NE Background: Sacubitril/Valsartan (S/V) is indicated in stable, symptomatic HFrEF as an alternate to an ACEI or ARB. Initiation of S/V requires planning and care coordination with relatively low rates of utilization despite a Class I-BR recommendation. Starting S/V early after a hospitalization for HF may increase utilization. Methods: A retrospective chart review of HF patients who were initiated on S/V either in-hospital or within 7 days after hospitalization for decompensated HF was conducted. Patients had to have all of the following at the time of S/V initiation: HFrEF with EF 40%; serum K+ 4.0 5.0; serum creatinine 1.5 mg/dl; and a systolic BP 110 mmHg. Clinical outcomes of the patients were evaluated and descriptive statistics were used to analyze the data. Results: A total of 27 patients who met the inclusion criteria were evaluated. S/V was initiated in-hospital in 8 patients and outpatient in 19 patients. Baseline characteristics were mean age 71 § 7 years, 74% men, 93% white, NYHA FC class III 85% and class IV 15%, and mean EF 29% § 4%. Twenty patients were on an ACEI and 7 were on an ARB. All patients were on a beta-blocker and 18 were on an aldosterone receptor antagonist. Twelve (44%) patients tolerated S/V at last follow-up (5 months). Fifteen (56%) patients discontinued S/V therapy during the first month of treatment. S/ V was discontinued for hypotension in 7 patients and hypotension with acute kidney injury (AKI) in 8 patients. AKI was most likely secondary to pre-renal azotemia with 6 of the 8 patients with BUN/creatinine ratios > 20:1. Hypotension and AKI resolved in all patients upon discontinuation of S/V. There were no significant differences between patients continuing versus patients discontinuing S/V other than location of S/V initiation. Only 2 of 8 (25%) patients initiated in hospital continued S/V therapy while 10 of 19 (53%) outpatients continued therapy. However, there was no difference in the number of days from hospitalization to start of S/V therapy between those tolerating (10.3 § 2.0 days) and not tolerating S/V therapy (9.7 § 1.9 days). Conclusions: Early initiation of S/V may lead to greater utilization of this Class I recommended therapy, but our data suggests early initiation after HF decompensation is not tolerated in a majority of HF patients. Hypotension and AKI are the primary reasons for intolerance.
073 Initiation of Sacubitril/Valsartan (S/V) in Patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and Compliance with Guideline-Directed (GD) Concomitant Medical Therapy for Heart Failure Chunlan Chang1, Xue Song2, Michelle Choi3, Carol Duffy1; 1Novartis, East Hanover, NJ; 2IBM Watson Health, Cambridge, MA; 3University of Maryland, Baltimore, MD Background: The 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure (HF) Treatment guides healthcare providers on treatment plans and discussions with patients with HFrEF. Data on concomitant GD medical therapy for HF pre and post S/V initiation in the real world is limited. Objective: To assess concomitant GD medical therapy for HF pre and post S/V initiation. Methods: All adult patients with 1 claim for S/V or angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) in 7/7/2015-5/31/2016 were identified from a large administrative claims database. Patients on S/V were assumed to have HFrEF based on its approved indication. Patients on ACEI/ARB had claims-based evidence of HFrEF. The index date was 1st claim for S/V (searched first) or ACEI/ARB. All patients had data for 24 months pre-index and 6 months post-index, unless inpatient death occurred. The uses of GD beta blockers (BB) and mineralocorticoid receptor antagonists (MRA) were assessed. Daily dose of the last fill of GD BB and MRA within 12-month pre S/ V initiation and up to 4 fills post S/V was classified into 4 levels: <25%, 2550%, 50-75% and >75% of GD target dose. McNemar’s tests were conducted on % of patients with GD medications pre- and post-index; Cochran-Armitage tests were for the trend of target dose levels for all patients. Results: A total of 956 patients had 1 claim for S/V (median age 64 years, 71% male) and 55,492 patients had 1 claim for ACEI/ARB (median age 70 years, 62% male). Compared to pre S/V initiation, fewer S/V patients had concomitant GD BB (post vs. pre: 84.1% vs 89.3%) or MRA (47.7% vs 52.1%) post S/V; both p<.001. In contrast, the ACEI/ARB cohort had no marked difference in post- vs pre-index use of GD BB (67.1% vs 68.5%) or MRA (21.5% vs 22.1%). In the S/V cohort, 50.8% of patients started S/V at 24/26 mg b.i.d., 35.7% at 49/51 mg b.i.d., and 11.5% at 97/103 mg b.i.d. During the median follow-up of 433 days, 36.8% of patients reached target maintenance dose of 97/103 mg b.i.d. Importantly, among patients who remained on GD BB or MRA post S/V, daily doses did not vary post vs pre S/ V initiation (all p>0.10). About 34-35% and >70% of patients received >75% of GD target daily dose for BB and MRA, respectively, across all fills (Figure 1). Conclusions: The majority of patients remained on GD BB or MRA with S/V; most continued at the same dose level of GD BB and MRA. Thus, in real-world practice, S/V is prescribed concomitantly with GD BB and MRA without the need for dose adjustment in the majority of cases.
074 An Analysis on Clinical Outcomes and Diuretic Requirements Following Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure with Reduced Ejection Fraction Natalie Pierson, Cheryl Abbas, Gordon Reeves; Thomas Jefferson University Hospital, Philadelphia, PA Background: A post-hoc analysis of the PARADIGM-HF clinical trial demonstrated treatment with sacubitril/valsartan resulted in a significant reduction in patients with worsening NYHA functional class, as compared to enalapril. Additional post-hoc analyses have revealed a reduction in intensification in outpatient diuretics, as well as a reduction in overall daily diuretic requirements, for patients treated with sacubitril/valsartan verses enalapril. Real world evidence is limited in analyzing patient experiences surrounding improvement in HF symptoms and diuretic usage. Methods: This analysis was a retrospective chart review of patients consecutively prescribed sacubitril/valsartan at the Jefferson Heart Institute from January 1, 2016 until January 31, 2017. Patient clinical outcomes and diuretic requirements were analyzed for 3 months following maintenance on any dose of sacubitril/valsartan for four weeks. Chart examinations reviewed documentation for improvements in heart failure (HF) symptoms, NYHA functional class, and LVEF, as well as changes in concomitant HF medications. Safety endpoints included symptomatic hypotension and an elevation in serum creatinine and/or potassium. Results: A total of 42 patients were included in the analysis. Thirty-six patients (85.7%) were titrated from their initial starting dose, although only 28 patients (66.7%) reached the targeted dose of 97/103mg twice daily. Fifty-seven percent of the patients (24/42) reported improvements in their HF-related symptoms, while 38.1% (16/42) of the patients demonstrated improvement NYHA functional classification. Thirty-six patients were concomitantly receiving loop diuretics during the initiation of sacubitril/valsartan, of whom 6 (16.7%) and 14 patients (38.9%) required discontinuation and dose reductions of loop diuretics, respectively. Twenty-two patients had a repeat ECHO after sacubitril/valsartan was initiated, fourteen of whom (63.6%) showed improvements in their LVEF. Two patients required discontinuation of therapy due to an adverse reaction; however, no other discontinuations were required from symptomatic hypotension, hyperkalemia or renal impairment. Sixteen patients (38%) experienced symptomatic hypotension, and 50% of those patients were not titrated to the target dose. Conclusion: Treatment with sacubitril/valsartan resulted in an improvement in patient-reported HF symptoms, NYHA functional class and LVEF. Although the majority of patients were maintained on diuretics post initiation of sacubitril/valsartan, daily dose reductions were observed. Patients did not require discontinuation of therapy as a result of symptomatic hypotension, hyperkalemia and/or renal impairment. Despite a small sample size, this retrospective analysis serves as an example of real world experience with initiating sacubitril/valsartan in patients with chronic HFrEF.
075 AG10, A Novel, Potent and Selective Transthyretin Stabilizer, is Well Tolerated at Doses Resulting in Target Therapeutic Blood Levels, and Demonstrates Clinical Proof-of-Concept in Healthy Volunteers Jennifer L. Hellawell1, Satish Rao1, Terry O’Reilly2, Rick Lumpkin1, Jesper Jernelius1, Daniel Gretler1, Uma Sinha1, Jonathan C. Fox1; 1Eidos Therapeutics, Inc., San Francisco, CA; 2Celerion, Inc., Tempe, AZ Introduction: AG10 is a novel, potent and selective oral transthyretin (TTR) stabilizer under clinical development to treat TTR amyloidosis (ATTR). Both mutant and