Presentation on theme: "Effect of Aliskiren on Postdischarge Outcomes Among Non-Diabetic Patients Hospitalized for Heart Failure: Insights from the ASTRONAUT Outcomes Trial Aldo."— Presentation transcript:
Effect of Aliskiren on Postdischarge Outcomes Among Non-Diabetic Patients Hospitalized for Heart Failure: Insights from the ASTRONAUT Outcomes Trial Aldo P. Maggioni, MD, FESC Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy On behalf of: Stephen J. Greene, MD; Gregg C. Fonarow, MD; Michael Böhm, MD; Faiez Zannad, MD; Scott D. Solomon, MD; Eldrin F. Lewis, MD; Fabio Baschiera, PhD; Tsushung A. Hua, PhD; Claudio R. Gimpelewicz, MD; Anastasia Lesogor, MD; Mihai Gheorghiade, MD; for the ASTRONAUT Investigators and Coordinators
Presenter Disclosure Information Dr. Maggioni: Serving in Committees of studies on Heart Failure sponsored by: Bayer, Abbott Vascular, Cardiorentis, Johnson & Johnson, Novartis Pharma AG
Study Organization Study Executive Committee: Mihai Gheorghiade, MD; Chair Aldo P. Maggioni, MD; Co-Chair Michael Böhm, MD Gregg C. Fonarow, MD Faiez Zannad, MD, PhD Study Data Monitoring Committee: Karl Swedberg, MD, PhD; Chair Jeffrey S. Borer, MD Bertram Pitt, MD Stuart Pocock, PhD Jean Rouleau, MD Central Endpoint Committee: Scott D. Solomon, MD; Chair Eldrin F. Lewis, MD; Co-Chair Peter Finn, MD Howard Hartley, MD Larry Weinrauch, MD Ebrahim Barkoudah, MD Kayode Odutayo, MD Study was funded by Novartis Pharma AG
Background and Rationale 1.Gheorghiade et al. JAMA. 2013;309(11):1125-35. ASTRONAUT explored the effect of aliskiren, a direct renin inhibitor, when added to standard therapy on the rate of CV death or HF re-hospitalization among hemodynamically stable hospitalized HF patients. 1 Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). The overall results were presented at the ACC 2013 and ESC HF 2013 and published in JAMA 1 ; the current presentation is focused on the effects of aliskiren in patients without DM (~60% of the study population).
Objectives Primary: CV death or HF re-hospitalization within 6 months Key Secondary: CV death or HF re-hospitalization within 12 months Secondary: All-cause mortality within 6 and 12 months Change in biomarkers from baseline (NT-proBNP, PRA, plasma troponin I, and plasma aldosterone) at 1, 6 and 12 months of follow up
Selection Criteria Inclusion criteria: Patients requiring hospitalization for worsening of chronic HF LVEF ≤40% BNP ≥400 pg/mL or NT-proBNP ≥1600 pg/mL SBP ≥110 mm Hg for at least 6 hours No use of IV vasodilators (except nitrates)/IV inotropes from the time of hospital presentation to randomization Exclusion criteria: Recent MI, cardiac surgery or stroke eGFR 5.0 mEq/L Hyponatremia <130 mEq/L, and Comorbid conditions with expected survival <3 years
Study Design Screening 2 weeks Randomization Placebo Aliskiren 300 mg Conventional therapy Aliskiren 150 mg Follow-up period Hospitalization for worsening chronic HF median: 5 daysmedian: 11.3 months
Safety profile in Non-DM Patients Aliskiren N = 489 n (%) Placebo N = 465 n (%) Aliskiren vs. Placebo relative risk (95% CI) P-value (2-sided) Rate of treatment discontinuation due to AEs Hyperkalemia16 (3.3)10 (2.2)1.52 (0.70-3.32) 0.32 Renal impairment or renal failure 19 (3.9)9 (1.9)2.01 (0.92-4.39) 0.09 Hypotension18 (3.7)9 (1.9)1.90 (0.86-4.19) 0.12 Maximum or minimum post-baseline values Potassium ≥6 (mmol/L)32 (6.5)26 (5.6)1.17 (0.71-1.93)0.59 eGFR <30 (mL/min/1.73 m 2 ) 46 (9.4)42 (9.0)1.04 (0.70-1.55)0.91
Limitations The major limitation of this work is that these results are based on a subgroup analysis. Therefore these results can be considered hypothesis generating only. An additional limitation is the definition of DM used. The presence or absence of underlying diabetes was determined solely by the investigator and it was not mandatory to use objective criteria.
Conclusions In the pre-specified subgroup of ASTRONAUT patients without DM representing 60% of study population, the addition of aliskiren to standard therapy appeared to improve post- discharge outcomes, serum biomarker profile and was generally well tolerated. In contrast, diabetic patients appeared to have worse post- discharge outcomes with aliskiren. Results suggest the potential of aliskiren in hospitalized HF patients without DM, where, despite of available therapies, post-discharge event rate remains high. Future prospective investigations are encouraged to confirm potential benefits of renin inhibition in the large cohort of hospitalized HF patients without DM.
Publication Aldo P. Maggioni and coauthors Effect of Aliskiren on Postdischarge Outcomes Among Diabetic and Non-diabetic Patients Hospitalized for Heart Failure: Insights from the ASTRONAUT Trial Published online September 2nd, 2013 Available at www. eurheartj.oxfordjournals.org Snapshot of published manuscript