Connor Iapoce

Highly purified eicosapentaenoic acid (EPA) reduced the risk of adverse cardiovascular events in patients with 

 with borderline statistical significance.

Meanwhile, highly purified EPA of 1,800 mg/day was significantly associated with a decreased risk of the composite of coronary events included in the secondary outcomes of the Randomized Trial for Evaluating the Secondary Prevention Efficacy of Combination Therapy (RESPECT-EPA).

“Present findings indicate a possible prognostic benefit of EPA at 1,800 mg/day in chronic CAD patients with statins whose EPA/arachidonic acid (AA) ratio was low at < 0.4,” said study author Hiroyuki Daida, MD, PhD, Juntendo University School of Medicine. 

The late-breaking findings were presented at the 

American Heart Association Scientific Sessions 2022

Previously, in 2005, the Japan EPA Lipid Intervention Study (JELIS) demonstrated a beneficial effect of highly purified EPA on cardiovascular outcomes in patients with and without CAD. Now, optimal medical therapy with high-intensity statins has become the gold standard of care for CAD patients, but there is a substantial residual risk.

Investigators noted the conflicting results in recent omega-3 fatty acid trials have created controversy over the relevance of EPA intervention alongside the latest optimal medical therapy. The clinical implications of serum EPA/arachidonic acid ratio as a biomarker has not been validated.

The RESPECT-EPA aimed to evaluate the effect of EPA on cardiovascular events in combination with statins and additionally addressed a prognostic implication of EPA/AA ratio for patients with CAD. Patients were required to receive statins for at least one month prior to inclusion and were 20 - 79 years old at the time of providing consent for the study.

The trial consisted of two parts, with an open-label randomized controlled trial (RCT) and biomarker study part (prospective cohort study design). The RCT included patients with low EPA/AA (lower than 0.4) and the patients were then randomized to highly purified EPA (icosapent ethyl; 1800 mg/day) or control.

Individuals in the high EPA/AA ratio (greater than or equal to 0.4) and the control group in the RCT part were included in the biomarker study to assess the usefulness of EPA/AA ratio as a biomarker for cardiovascular events prediction.

The study’s primary endpoints were a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, unstable angina pectoris, and clinically indicated coronary revascularization. Secondary endpoints included composite events of CAD, composite events of stroke, and events related to death.

In the RCT, a total of 1225 patients were allocated to the EPA group and 1235 patients to the control group. Baseline characteristics were similar between the EPA and control groups and the baseline median EPA/AA ratio was 0.243 and 0.235, respectively.

For the biomarker study, a total of 1314 patients with high EPA/AA ratio were registered and their baseline median EPA/AA ratio was 0.577. It consisted of a median follow-up period was 5 years.

Within the RCT, the primary outcome occurred in 112 in the EPA group and 155 in the control group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62 - 1.00; stratified log-rank 

-value = .055). Meanwhile, the secondary endpoint of coronary events occurred in 81 patients in the EPA group and 120 in the control group (HR, 0.73; 95% CI, 0.55 - 0.97; stratified log-rank 

The HR for all-cause mortality was 0.682 (95% CI, 0.385 - 1.208; stratified log-rank 

-value = .1928) and the HR for cardiovascular mortality was 0.888 (95% CI, 0.625 - 1.262; stratified log-rank 

Investigators reported a significantly higher incidence of new onset atrial fibrillation in the EPA group compared to the control group.

“Randomized Trial for Evaluating Secondary Prevention Efficacy of Combination Therapy -Statin and Eicosapentaenoic Acid,” was presented at 

Articles

The late-breaking findings suggest the potential prognostic benefit of highly purified EPA in patients with chronic CAD with a low EPA/AA ratio. 


EPA Reaches Borderline Statistical Significance in RESPECT-EPA Trial 

Sodium-glucose co-transporter 2 (SGLT2) inhibition with empagliflozin did not lead to significant changes in left ventricular (LV) structure or function among individuals without diabetes or significant 

The findings from the Empagliflozin and Cardiac Remodeling in People Without Diabetes (EMPA-HEART 2 CardioLink-7) trial were presented in a session at the 

American Heart Association (AHA) Scientific Sessions 2022

“This suggests that in a broader and potentially lower risk cohort of individuals without diabetes, significant LV hypertrophy and a median baseline NT-proBNP of ~ 50pg/mL, short-term SGLT2 inhibition (e.g., the 6 months study duration in EMPA-HEART 2) is unlikely to be associated with changes in LV structure or function,” wrote study author Subodh Verma, MD, PhD, Division of Cardiac Surgery, St. Michael’s Hospital, University of Toronto.

As SGLT2 inhibitors have proven benefit across the spectrum of heart failure, it has been considered that the medication class may lead to greater benefit if introduced earlier in the natural history of heart failure. 

The randomized trial compared empagliflozin to placebo in a cohort without diabetes and not enriched for significant heart failure and evaluated the change in left ventricular mass over 6-months by cardiac magnetic resonance imaging (cMRI). Study enrollment occurred between April 2021 and January 2022 at two sites in Canada and one site in Taiwan.

The primary outcome was the change in left ventricular mass indexed (LVMI) to baseline body surface area between the baseline and month 6 visits in the empagliflozin and placebo groups. Further measures included in the 6-month between-group changes in LV end-diastolic and end-systolic volume and LVEF.

Of the 227 individuals who provided informed consent, 169 were randomized to either empagliflozin 10 mg/day (n = 85) or placebo (n = 84) for six months. The study population consisted of 141 men (83%) and had a mean age of 59.3 ± 10.5 years. Baseline LVMI was reported as 63.2 ± 17.9 g/m2 and 63.8 ± 14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively.

The difference in LV mass at 6 months in the empagliflozin group compared to the placebo group adjusted for baseline LV mass was -0.83 (95% confidence interval [CI], -4.5 to 2.8; 

 = .65). Regarding the primary outcome, the difference in LVMi at 6 months in the empagliflozin group compared with the placebo group, adjusted for baseline LVMi, was -0.30 mg (95% CI, -2.1 to 1.5; 

Investigators had enrolled a population without significant heart failure, as explained by the baseline NT-proBNP levels. The median baseline NT-proBNP was 51 pg/mL and 55 pg/mL for the empagliflozin- and placebo-assigned groups, respectively.

Data show the 6-month treatment effect of empagliflozin versus placebo on blood pressure and NT-proBNP were -1.3 mmHg (95% CI, -5.2 to 2.6 mmHg; 

 = .52), 0.69 mmHg (95% CI, -1.9 to 3.3 mmHg; 

 = .60), and -6.1 pg/mL (95% CI, -37.0 to 24.8 pg/mL; 

 = .70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively.

There were no clinically meaningful between-group differences in LV volumes or ejection fraction reported by investigators. Investigators noted that empagliflozin was well-tolerated and there were comparable adverse outcome rates between study arms.

The study, “Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART2 CardioLink-7 Randomized Clinical Trial,” was published in 

Over a six-month period, SGLT2 inhibition with empagliflozin did not change left ventricular structure or function compared with placebo in people without diabetes or significant heart failure. 

Empagliflozin Did Not Change Left Ventricular Structure, Function in People Without Diabetes 

A hospital-based strategy to aid clinical decision making was associated with a lower risk of a composite of death from any cause or hospitalization for cardiovascular causes compared with usual care for patients with 

Within 30 days after presentation, the intervention led to a 12% lower risk of the outcomes and led to a lower risk of death from any cause or hospitalization for cardiovascular causes within 20 months.

“Implementation of this approach may lead to a pathway for early discharge from the hospital or emergency department and improved patient outcomes,” wrote lead author Douglas S. Lee, MD, PhD, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University of Toronto.

The late-breaking findings were presented at the American Heart Association Scientific Sessions 2022 in Chicago.

Individuals who present to the emergency department with acute heart failure are often hospitalized, with clinicians often relying on clinical judgment to determine the path forward to admit or discharge patients. As a result, some high-risk patients are discharged home from the emergency department and some lower-risk patients are hospitalized, when they could be discharged and followed in ambulatory care.

The stepped-wedge, cluster-randomized, Comparison of Outcomes and Access to Care for Heart Failure (COACH) trial randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase to the intervention phase. The intervention included a point-of-care algorithm (Emergency Heart Failure Mortality Risk Grade for 30-day mortality [EHMRG30-ST]) to strategy patients with acute heart failure according to risk of death.

Lower risk patients who were discharged from the emergency department or after a short observation period of 3 days or less in the hospital and received standardized outpatient care, while high-risk patients were admitted to the hospital. The acute HF risk stratification algorithm was housed on a central server and was accessible to sites only after crossover to active intervention.

The two co-primary outcomes were the 30-day composite of all-cause death or cardiovascular hospitalization (early) and 20-month composite of all-cause death or cardiovascular hospitalization (late). The outcomes were determined by linking clinically obtained data with administrative databases.

The statistical analyses used Cox proportional hazards models for time-to-event and logistic regression for binary outcomes. The models adjusted for step, hospital teaching status, annual HF patient volume, and accounted for within-hospital clustering.

A total of 5452 patients were enrolled in the trial, made up of 2972 patients during the control phase and 2480 patients during the intervention phase.

Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) enrolled during the control phase (adjusted hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78 - 0.99; 

Then, within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients enrolled during the control phase (adjusted HR, 0.95; 95% CI, 0.92 to 0.99).

Investigators noted fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge.

“The ability to prognosticate more accurately may enable physicians to make informed decisions about appropriate care settings, may enhance safety by reducing discharge of high-risk patients, and may improve efficiency by reducing admission of lower-risk patients,” added Lee.

The study “Trial of an Intervention to Improve Acute Heart Failure Outcomes,” was published in 

Risk stratification in the emergency department led to a 12% lower risk of death from any cause or hospitalization for cardiovascular causes compared with usual care. 

Connor Iapoce

Articles

EPA Reaches Borderline Statistical Significance in RESPECT-EPA Trial

Empagliflozin Did Not Change Left Ventricular Structure, Function in People Without Diabetes

Hospital-Based Strategy Lowers Risk of Death in Patients with Acute Heart Failure