The studies mentioned below were presented during the American Heart Association Scientific Sessions 2015 in Orlando (http://my.americanheart.org/professional/Sessions/ScientificSessions/Scientific-Sessions_UCM_316900_SubHomePage.jsp) and either published as congress abstracts or original publications (see citations). We have selected trials that might be of general importance and those that may be of particular interest to the basic scientist.
The findings of the so-called SPRINT-Trial were maybe the most groundbreaking of the congress. This trial included 9361 patients with hypertension and an increased cardiovascular risk, but without diabetes. The aim of this study was to examine the effect of more intensive high blood pressure treatment than is currently recommended. Therefore, patients were either included into an intensive treatment group (goal SBP <120 mmHg) or a standard group (goal SBP <140 mmHg). The study was stopped early after a median follow-up of ~three years due to a significantly lower rate of the primary composite outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) in the intensive-treatment group. Even all-cause mortality was significantly lower in the intensive-treatment group. As expected, rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. The authors therefore conclude that, among patients at high risk of cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause.
N Engl J Med. 2015. 373:2103-16.
The novel beta 3–adrenoceptor agonist mirabegron is already approved for the treatment of overactive bladder and thus is considered to be safe in humans. Beta 3–adrenoceptor agonist stimulates the Na/K pump through the NO/cGMP/PKG pathway-mediating Na extrusion. In BEAT-HF, this drug was investigated in subjects with chronic heart failure. A 6-month, pilot study included 70 patients suffering from chronic heart failure. The overall tolerability of the drug was good, without relevant effects on blood pressure or heart rate. There was no general improved left ventricular ejection fraction compared with placebo. However, patients with a more reduced ejection fraction below 40% were more likely to experience an increased ejection fraction when treated with mirabegon.
This study aimed at preventing the vascular depletion of nitric oxide as a possible target for operators looking to prevent acute kidney injury due to extended heart surgery. 2017 patients were randomized and possibly treated with nitric oxide during open heart surgery in one centre in China. There was a reduction of ~22% of the serum creatinine within two days of surgery in subjects that were treated with nitric oxide, indicating an attenuated kidney injury.
In this trial, Omecamtiv, a myosin-activating drug, was investigated in patients. 448 patients with chronic heart failure were randomized to either Omecamtiv or placebo in addition to standard heart failure therapy. The side-effect profile of the drug was similar to placebo. Patients treated with Omecamtiv had significant improvements in systolic ejection time, stroke volume, and natriuretic-peptide levels. Unfortunately patients who received Omecamtiv showed a rise in troponin levels by week 20 that returned to baseline later in this trial. Thus, this cardiac myosin activator seems to boost ventricular function by prolonging systolic ejection time.
Andexanet was designed to reverse the anticoagulant effects of factor Xa inhibitors. Healthy older volunteers were treated with standard doses of the novel anticoagulant agents, apixaban or rivaroxaban. Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in these participants, within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects.
N Engl J Med. 2015. Epub ahead of print.
This trial investigated the effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard therapy, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk. 7020 patients were randomly assigned to receive different dosages of empagliflozin or placebo. Remarkably, the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was significantly reduced in the empagliflozin group.
N Engl J Med. 2015. 373:2117-28.
The Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy trial included 120 women who received anthracycline-containing chemotherapy. Subjects were randomized to receive daily doses of candesartan or matching placebo. The results show that those who were in the intervention group had a more preserved left ventricular ejection fraction than patients who received placebo. Therefore, neurohormonal blockade may preserve left ventricular systolic function during/after chemotherapy with high-dose anthracyclines, as well as trastuzumab, a frequent clinical problem.
The glucagonlike peptide-1 (GLP-1) receptor agonist liraglutide was investigated for 6 months in a 300 patient trial in subjects with advanced heart failure. There was no relevant difference regarding death and rehospitalization between the liraglutide and placebo group. However, as predicted, liraglutide improved glycaemic control and led to weight loss in diabetic patients of this trial.
This trial investigated the outcomes of resuscitated patients after continuous chest compressions with positive-pressure ventilation compared to compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations. In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions.
N Engl J Med. 2015. 373:2203-14.
This trial compared the effect of isosorbide mononitrate or placebo on daily activity in patients with HFpEF. 110 patients were randomized to either nitrates or placebo for six weeks in a crossover design. The primary end point was the daily activity level of patients. Surprisingly, patients in the intervention group were less active and did not have better quality of life or submaximal exercise capacity than patients who received placebo.
N Engl J Med. 2015. 373:2314-2324
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