Key Points:

• This trial randomized 6,000 patients with high bleeding risk or acute coronary syndrome undergoing planned PCI to a strategy of 3.75mg of prasugrel or DAPT with aspirin 81-100 mg and prasugrel 3.75mg, following a prasugrel load in both arms.
• At 1 month, prasugrel alone failed to demonstrate superiority for the co-primary endpoint of major bleeding. However, the aspirin-free strategy was non-inferior to DAPT for the co-primary endpoint of cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke).
• DAPT remains the standard strategy post-PCI even in the current era with the newest generation of drug-eluting stents.

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Key Points

• The FIRE trial aimed to address the lack of evidence regarding complete revascularization in older MI patients and examined the superiority of complete revascularization based on coronary physiology.
• The trial enrolled 1,445 patients with a median age of 80, and the primary outcome (death, MI, stroke, or ischemia-driven coronary revascularization) occurred in fewer patients in the physiology-guided complete revascularization group compared to the culprit-only group.
• Physiology-guided complete revascularization reduces ischemic events compared with culprit-only revascularization in myocardial infarction patients aged 75 years or older with multivessel disease.

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Key Points:

• Iron-deficiency is common in heart failure (HF) and associated with increased mortality and hospitalization.
• Previous trials of intravenous (IV) iron in the form of ferric carboxymaltose (FCM) in iron-deficient HF patients have shown improvements in symptoms and quality of life, but effects on clinical events have been unclear.
• This meta-analysis pooled data from three randomized controlled trials (RCTs) – CONFIRM-HF, AFFIRM-HF, and HEART-FID – to assess both a composite endpoint of total CV hospitalizations and death, as well as a composite endpoint of total HF hospitalizations and CV death through 52 weeks.
• In iron-deficient patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), IV FCM is associated with reduced risk of composite outcome of total cardiovascular (CV) hospitalization and death through 52 weeks compared with placebo.

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Key Points:

• The use of ECLS has increased substantially over the past decade despite stagnant, high mortality in cardiogenic shock.
• This multicenter randomized trial compared ECLS with control in patients with acute MI-related cardiogenic shock. The primary endpoint was 30-day all-cause mortality.
• There were no differences in the primary endpoint of all-cause mortality between ECLS and placebo; however, ECLS resulted in higher rates of moderate-to-severe bleeding and peripheral ischemia requiring intervention.

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Key Points:

• Qiliqiangxin is a traditional Chinese herbal medicine extract which has been approved since 2004 for the treatment of HF in China.
• This multicenter, double-blind, placebo-controlled trial compared qiliqiangxin with placebo amongst patients with HFrEF (EF<40%). The primary endpoint was a composite of CV death and HF hospitalizations.
• Over a median follow-up of 18 months, qiliqiangxin use resulted in a reduction in the composite primary endpoint.

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Key Points:

• Prior data suggest that heart failure with reduced ejection fraction (HFrEF) patients with iron deficiency receiving IV iron supplementation had improvement in exercise capacity and HF hospitalizations, but the long-term safety and efficacy of the treatment is unknown.
• The HEART-FID trial was a double-blind, placebo-controlled event-driven randomized trial assessing whether there would be improvement in the incidence of death and hospitalization for heart failure or 6-minute walk distance with ferric carboxymaltose therapy compared with placebo in patients with heart failure with a reduced ejection fraction and iron deficiency.
• Patients receiving IV ferric carboxymaltose (FCM) had slightly fewer all-cause mortality events, HF hospitalizations and modestly longer 6-minute walk duration. However,there was no apparent difference in the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance.
• Overall FCM supplementation is safe and shows potential clinical benefits; further context can be obtained via pooled analysis with other IV FCM trials.

Iron deficiency has a prevalence of nearly 50% among patients with heart failure with reduced ejection fraction (HFrEF) and leads to impaired health-related quality of life, worsening heart failure (HF) symptoms, and adverse outcomes. The mechanism for iron deficiency in HF is not fully understood though thought to be related to reduction in iron intake as well as absorption and mobilization with increased loss as well. Treatment with intravenous (IV) ferric carboxymaltose (FCM) has previously been shown to improve HF patients’ symptoms and functional capacity. Notably, evidence regarding the utility of IV FCM for improving clinical outcomes such as morbidity and mortality is more limited. Information regarding the long-term efficacy and safety of IV iron infusions is also limited. Furthermore, the majority of available data on the subject was obtained in Europe and excluded other geographic HF populations.

The HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency) (NCT03037931) was a multicenter, randomized, double-blind, placebo-controlled trial that sought to assess the efficacy and safety of IV FCM in the treatment of symptomatic patients in HFrEF with iron deficiency over a period of at least 12 months. Over three thousand patients were randomized at 281 study locations in various geographic regions that included North America, Australia, New Zealand, and Europe. Heart failure patients had ejection fraction (EF) ≤40% within 24 months or ≤30% within 36 months of screening and NYHA Class II-IV symptoms on maximally tolerated background therapy for ≥2 weeks before randomization. They had to have documented HF hospitalization within 12 months of enrollment or elevated N-terminal-pro-brain natriuretic peptide within 90 days of randomization. Criteria for iron deficiency were ferritin <100 ng/mL or 100 to 300 ng/mL with a transferrin saturation <20% with hemoglobin >9.0 g/dL and <13.5 g/dL (females) or <15.0 g/dL (males). Importantly, the trial included those patients with and without anemia. Active bleeding or recent blood transfusion was prohibitive for enrollment.

Eligible patients were given an initial 28-day screening period and then randomized in a 1:1 ratio to receive FCM or placebo. They were then given the study drug on day 0 and 7 and followed up with additional study visits at 3 month intervals. Patients were eligible for additional dosing of the drug every 6 months as needed. HEART-FID trial clinical endpoints included a hierarchical composite of death and HF hospitalizations in the first 12 months, and change in 6 minute walk test (6-MWT) distance at 6 months. Notably a significance level of 0.01 was pre-specified for regulatory purposes by the US Food and Drug Administration (FDA).

Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group, and a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12. The mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon–Mann–Whitney P=0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients.

Presented at the 2023 European Society of Cardiology Congress on August 26^th by Dr. Robert Mentz (Duke Clinical Research Institute, Durham, NC) the HEART-FID trial data showed that administration of FCM resulted in modest improvement for the primary hierarchical endpoint which narrowly missed statistical significance (P=0.019).. When reporting the win ratio in order to translate the endpoint into clinical significance, there were 20% more wins with FCM than placebo for all-cause mortality. When assessing heart failure hospitalizations in those without a death event, there were similar wins in both groups. Change in 6MWT slightly benefited the FCM group. There was a similar percentage of treatment emergent adverse events in each group.

Overall Dr. Mentz states that there was “modest improvement” in the FCM group compared to placebo but importantly IV iron supplementation showed “numerical improvements in mortality.” He goes on to say, “FCM is safe and we build on the prior data showing benefit in quality of life and exercise capacity [with FCM]. Each component of the primary endpoint favors FCM.” He believes that the importance of this study is in providing “another tool in our toolkit in addition to quadruple therapy specifically for HFrEF patients with iron deficiency.” He stated that one significant advantage of FCM is that it does not involve another daily medication and can be administered in clinic in a straightforward way to produce net benefit. Overall, FCM can be used clinically for patients with HFrEF and iron deficiency to help them feel and function better with evidence of a clinical outcome benefit as well. The trial results were simultaneously published in The New England Journal of Medicine.

Key Points:

• A high burden of right ventricular pacing among patients with heart failure patients with reduced ejection fraction is known to cause left ventricular dyssynchrony and progressive dysfunction, yet definitive evidence has been lacking to inform the timing of upgrade to CRT devices.
• The BUDAPEST-CRT Upgrade Study randomized 360 patients with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and RV pacing burden ≥ 20% to either CRT-D (n=215) or traditional ICD (n=145). The primary endpoint was a composite of all-cause mortality, a first HHF event, or <15% reduction in LVESV at 12 months.
• This trial showed a significant reduction in the primary composite endpoint (32.4% in the CRT-D arm versus 78.9% in the ICD arm, aOR = 0.11, 95% CI 0.06-0.19, p-value <0.001), as well as in several individual secondary endpoints. Taken together, these findings support the clinical practice to promptly pursue CRT upgrade among HFrEF patients with intermittent or permanent RV pacing.

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Key Points:

• More than 80% of patients with HFpEF are overweight or obese, but there has not yet been a study examining the use of weight-loss agents in body weight reduction or HF symptomatology in HFpEF.
• In the Step-HFpEF study, subcutaneous once-weekly semaglutide was compared with placebo in patients with HFpEF and obesity. The two primary endpoints were change of KCCQ-CCS and body weight from baseline after 52 weeks of treatment.
• Semaglutide use resulted in a significant reduction in both heart failure symptomatology and body weight at 52 weeks.

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Key Points

• This trial randomizing patients aged 55 or older to colchicine or placebo following non-cardiac thoracic surgery found no difference in the co-primary endpoints of atrial fibrillation or myocardial injury, but post-hoc analyses indicated benefit in composite outcomes without a signal for increased harm.
• Colchicine increased risk of diarrhea, but patients reported that these symptoms were mostly temporary and benign.
• Further research is needed to explore the encouraging and consistent trend of fewer cardiovascular events with colchicine after non-cardiac surgery.

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Key Points

• This trial randomized elderly patients without a known diagnosis of atrial fibrillation with device-detected atrial high-rate episodes (AHREs) and a median CHA2DS2VASC of 4 to edoxaban or placebo.
• The study was stopped early due to safety concerns and trend towards futility for efficacy after enrollment of all planned patients.
• Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not result in lower incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo. Rather, it was associated with a higher incidence of a composite of death or major bleeding.
• The results indicate that patients with AHREs on their implanted device should not be prescribed anticoagulation unless atrial fibrillation is diagnosed on surface ECG. However, the stroke rates in the control arm were lower than expected.

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