ESC Congress 2016 - 35

Your FREE access to ESC Congress content all year long www.escardio.org/365 ESC CONGRESS 2016 IN REVIEW Figure 1. In-Hospital Worsening HF is Associated with Release of Cardiac Troponin and Increased Risk of Death In-hospital worsening heart failure Release of cardiac troponin Cardiovascular mortality Abnormal calcium handling can cause cardiac dysfunction. Dr Butler noted that HNO enhances the activity of intracellular Ca2+ cycling proteins, augmenting maximal force without altering actomyosin ATPase activity. It also exerts inotrope, lusitrope, and vasodilator myocardial effects, in part by activation of sarcoplasmic reticulum calcium ATPase and does so without inducing tachycardia or increasing oxygen consumption. In a dose ranging Phase 2a study, 6-hour intravenous dosages of CXL-1427 (≥ 5 µg/kg/min) resulted in a significant (~5 mm Hg; P < .01) reduction of time-averaged pulmonary capillary wedge pressure (PCWP) in patients hospitalized for advanced HF. CXL-1427 reduced PCWP by a maximum of 4.8-6.9 mm Hg across the treatment groups, versus 2.0 mm Hg in the placebo group. Cardiac index and stroke volume increased, while mean arterial pressure decreased with the study drug. There were no increases in h eart rate with CXL-1427 versus placebo, and there were no cases of arrhythmia during infusion. No changes in circulating B-type natriuretic peptide levels or renal function markers were observed, and there were no CXL-1427related toxicities, aside from occasional headaches during infusion [Mitrovic V. Heart Failure 2016. London, UK]. Gerasimos Filippatos, MD, University Hospital Attikon, Athens, Greece, discussed the benefits and risks of mineralocorticoid receptor antagonists (MRAs) in patients with HF. MRAs have proven benefit for patients with symptomatic HF with reduced ejection fraction, yet only 32.2% of American patients eligible for treatment receive MRAs, usually following hospital discharge. Early studies reported that the MRA, spironolactone, added to an angiotensin-converting enzyme (ACE) inhibitor, substantially reduced the risk of both morbidity and death among patients with severe HF [Pitt B et al. N Engl J Med. 1999]. However, studies have reported an increase in the risk of hyperkalemia-associated morbidity and mortality with the combined use of these agents especially in HF patients with renal dysfunction. In another study, Pitt and colleagues reported an increased risk of worsening renal function with another MRA (eplerenone), which led the search for newer safer MRAs. Finerenone is a potent, non-steroidal, selective MRA that is as effective as spironolactone, but is associated with lower incidences of hyperkalemia and worsening renal failure [Pitt B et al. Eur Heart J. 2013]. In the ARTS-HF study [NCT01807221] finerenone (10-20 mg) decreased the level of plasma N-terminal pro-B-type natriuretic peptide by > 30% [Filippatos G et al. Eur Heart J. 2016]. Although exploratory, the incidence of the composite clinical endpoint of death from any cause, CV hospitalizations, or emergency presentation was also lower in the finerenone 10-20 mg dose group. (Figure 2) These findings need to be confirmed in larger and longer studies. In addition to new MRAs, new uses for old MRAs are being researched. Spironolactone is being studied in HF patients with preserved ejection fraction (EF ≥ 40%). Figure 2. Effects of Finerenone on Clinical Outcomes in HF Patients Study period Follow-up 100 Probability (%) 90 80 70 60 50 Eplerenone (n = 207) Finerenone 7.5-15 mg (n = 158) Finereone 2.5- 5 mg(n = 162) Finerenone 10-20 mg (n = 160) Finereone 5 -10 mg (n = 157) Finerenone 15-20 mg (n = 158) 0 0 10 20 30 40 50 60 70 80 90 100 110 120 Time (days) Reprinted from Filippatos G et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney Number at risk: disease. Eur Heart J.Eplerenone 2016;37(27):2105-2114. By permission of Oxford University Press on behalf of 121 the European Society of Cardiology. 207 doi:10.1093/eurheartj/ehw132. 161 134 Finerenone 2.5-5 mg Finerenone 5-10 mg Finerenone 7.5-15 mg Finerenone 10-20 mg Finerenone 15-20 mg 162 157 158 160 158 122 130 138 139 129 103 113 117 126 118Official 90 105 96 107 95 Peer-Reviewed Highlights From ESC Congress 2016 35 http://www.escardio.org/365

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