Late breaking science presented at AHA 2020

SOLOIST-WHF trial

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular (CV) causes among patients with chronic heart failure. SOLOIST-WHF tested a SGLT2 inhibitor in 1222 patients with type 2 diabetes mellitus recently hospitalized for worsening heart failure. Patients were randomized to receive sotagliflozin or placebo, before or shortly after discharge, and followed for a median of 9 months. Sotagliflozin therapy resulted in a significantly lower total number of deaths from CV causes and hospitalizations and urgent visits for heart failure than placebo.

GALACTIC-HF trial

The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction (HF-rEF). In GALACTIC-HF, 8256 inpatients and outpatients with HF-rEF received omecamtiv mecarbil (using pharmacokinetic-guided doses) or placebo during a median of 22 months in addition to standard of care. Omecamtiv mecarbil therapy was associated with a significant reduction in the primary outcome, which was the composite of a first heart failure event (hospitalization or urgent visit for heart failure) or death from CV causes.

HARP study

Myocardial infarction with non-obstructive lesions in the coronary arteries (MINOCA) is frequently observed in women. The HARP study, an international, multicenter, prospective study including 301 women with suspected MINOCA, evaluated the usefulness of optical coherence tomography (OCT) and cardiovascular magnetic resonance (CMR) to assess the mechanisms underlying MINOCA. MINOCA was diagnosed in 170 women. OCT detected an unstable coronary plaque in 46% of patients while CMR identified an ischemic cause in 53% of patients and a non-ischemic cause in an additional 20% (including Tako-tsubo syndrome, myocarditis or non-ischemic cardiomyopathy). The combined use of both modalities led to the diagnosis of an ischemic origin of MINOCA in 2/3 of the patients, and this finding has the potential to guide medical therapy for secondary prevention.

RIVER trial

Data on the efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and a bioprosthetic mitral valve are derived from small samples in sub-group analyses of pivotal trials of apixaban and edoxaban, and a pilot trial of dabigatran. The RIVER trial randomized 1005 patients with these characteristics, from 49 sites in Brazil, to rivaroxaban 20 mg once daily or warfarin (target international normalized ratio between 2.0-3.0). Rivaroxaban was non-inferior to warfarin with respect to the mean time until the occurrence of clinical events (death, major cardiovascular events, or major bleeding at 12 months).

OMEMI trial

OMEMI enrolled 1207 patients, 70-82 years old and with a recent acute myocardial infarction. Patients were randomized to 1.8 g marine n-3 polyunsaturated fatty acids (PUFA) (930 mg EPA and 660 mg DHA) or placebo (corn oil) daily added to standard of care secondary prevention, and were followed up for 2 years for the occurrence of non-fatal acute myocardial infarction, unscheduled revascularization, stroke, all-cause death, and heart failure hospitalization. Marine PUFA had no effect on the rate neither of clinical events nor of major bleeding.

SAMSON trial

Patients frequently complain of side effects of statins, which often lead to discontinuation of the treatment, and a subsequent increase in the risk of CV events. The SAMSON trial, a double-blind, three-group, N-of-1 trial, tested the nocebo effect of statin therapy in 60 patients who had previously discontinued statins because of side effects, mainly myalgia. The trial demonstrated that 90% of the symptoms elicited by statins were also reported while on placebo. Half the trial patients were able to successfully restart statins.

Evinacumab in Patients with Refractory Hypercholesterolemia

Treatment goals for low-density lipoprotein cholesterol (LDL-c) are difficult to achieve in some patients with heterozygous familial hypercholesterolemia despite treatment with a statin at a maximum tolerated dose, ezetimibe, and a proprotein convertase subtilisin-kexin type 9 inhibitor. Evinacumab, a human monoclonal antibody that inhibits angiopoietin-like 3, which can be administered intravenously or subcutaneously, led to a 50% reduction of the LDL-c levels as early as 2 weeks after starting the treatment and the effects were sustained after 16 weeks.

THALES trial exploratory analysis

The addition of ticagrelor to aspirin in patients with minor to moderate noncardioembolic ischemic stroke or high risk transient ischemic attack who were not treated with thrombolysis was associated with a significant reduction of the risk of stroke or death at 30 days, but also with a significant increase in severe bleeding. An exploratory analysis of this trial found a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis of the cervicocranial vasculature than in those without. In this subgroup of patients, ticagrelor added to aspirin provided a clinically meaningful benefit without increasing the risk of severe bleeding.

EXPLORER-HCM CMR substudy analysis

Mavacamten, a cardiac myosin inhibitor that reduces actin myosin cross-bridge formation, improved exercise capacity, left ventricular outflow tract gradients, symptoms, and health status in patients with symptomatic obstructive hypertrophic cardiomyopathy in the EXPLORER-HCM trial (presented at ESC 2020). This substudy shows that mavacamten induced significant reductions in left ventricular mass index, wall thickness and left atrial volume but did not change myocardial fibrosis over 30 days of follow-up.

FIDELIO-DKD substudy analysis

The FIDELIO-DKD trial showed that finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, improved kidney and CV outcomes in 5674 patients with chronic kidney disease (CKD) and type 2 diabetes mellitus on optimized renin-angiotensin system blockade. CKD was defined as moderately elevated albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30–<300 mg/g) and an eGFR ≥25–<60 mL/min, if a history of diabetic retinopathy was known, or severely elevated albuminuria (UACR ≥300–≤5000 mg/g) and an eGFR ≥25–<75 mL/min. In a prespecified subgroup analysis, finerenone lowered the risk of CV events (time to first onset of CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) in patients both with and without a history of CVD.