Key Points:

• Iron deficiency is common in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with worse outcomes.
• The FAIR-HF2 trial assessed the impact of intravenous iron supplementation on cardiovascular outcomes and quality of life in iron-deficient HFrEF patients.
• Intravenous iron failed to meet its primary endpoints of cardiovascular death or heart failure hospitalization, but it significantly improved quality of life, particularly in the first year of treatment.
• A meta-analysis incorporating over 7,000 patients confirmed a benefit of intravenous iron supplementation in HFrEF, supporting current guideline recommendations.

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KEY POINTS:

• Ouabain, a cardiac glycoside that is structurally similar to digoxin, has been shown to impair renal function in animal models. This finding suggests that Digifab, which binds to ouabain receptors, may help prevent AKI
• Digifab, an antidote for digoxin toxicity, was associated with a lower incidence of AKI in patients with high levels of endogenous ouabain undergoing CABG, but did not significantly impact eGFR 

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Key Points:

• Small retrospective studies of critically ill adults have shown pulse oximetry levels different by race
• No large prospective study has shown possible difference in pulse oximetry among darker skinned individuals
• The EquiOx study found that among critically ill adults, there were higher rates of overestimated pulse oximetry among darker skinned individuals
• This is the first large study to demonstrate findings of pulse oximetry bias, and future studies may benefit from expansion to other relevant populations

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Key Points:

• Hypertension (HTN), a major risk factor for cardiovascular disease, remains uncontrolled in many groups
• Lorundostat is an aldosterone synthase inhibitor, a novel anti-hypertensive agent that has shown some efficacy and safety in HTN treatment
• The ADVANCE-HTN trial was a multicenter randomized controlled trial evaluating the blood pressure lowering effect of lorundostat in uncontrolled and resistant HTN, finding an additional 8 mmHg decrease in 24-hour SBP compared to placebo
• This trial suggests that novel anti-hypertensive agents, particularly targeting aldosterone production, may be beneficial in HTN treatment and possibly cardiovascular risk reduction

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KEY POINTS:

• Significant bleeding is a common complication of cardiac surgery. Frozen plasma is the standard therapy but prothrombin complex concentrate offers an alternative treatment option.
• In the Factor Replacement in Surgery study (FARES II) patients experiencing significant bleeding during cardiac surgery who received PCC were 44% less likely to require additional intervention to control bleeding, compared to frozen plasma.

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KEY POINTS:

• SGLT2 inhibitors reduce admission for heart failure exacerbations.
• Clinical trials for SGLT2 inhibitors have historically excluded patients with aortic stenosis, a group with high rates of heart failure.
• In this prospective, randomized, open-label trial, elderly patients started on dapagliflozin shortly after TAVI had lower rates of all cause death or heart failure exacerbations at both 3 months and at 1 year compared to standard care.

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Key Points

• After DES placement, guidelines recommend considering shorter DAPT duration (e.g. 1-3 months) for those with high bleeding risk (HBR) and longer DAPT duration (e.g., 3-12 months) for those with low-bleeding risk (LBR). However, there is no randomized evidence comparing DAPT duration by bleeding risk category. 
• HOST-BR is the first study to stratify patients by bleeding risk and then randomize them to different DAPT durations. 
• Approximately ~1600 HBR patients were randomized to either 1 or 3 months of DAPT, and ~3300 LBR patients were randomized to either 3 or 12 months of DAPT after DES placement. The co-primary, hierarchical endpoints were net adverse clinical events (NACE; a composite of all-cause death, MI, stent thrombosis, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCE), and bleeding at 12 months. 
• Among HBR patients, a DAPT duration of 1 month was inferior to 3 months for both NACE and MAACE, without a significant improvement in bleeding. Among LBR patients, a DAPT duration of 3 months reduced bleeding compared with 12 months of DAPT, without increasing NACE or MAACE. 
• Therefore, 3 months of DAPT appeared to be the optimal duration for both low- and high- bleeding risk populations after PCI with DES. Limitations include generalizability beyond South Korea, as clopidogrel is preferentially used over ticagrelor in this population. 

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Key Points

• Injectable semaglutide, a GLP-1 receptor agonist, reduces CV events in patients with T2DM, however whether the oral form of semaglutide confers the same CV risk reduction is uncertain.
• The SOUL trial randomized 9650 participants age ≥50 with T2DM and established CAD, cerebrovascular disease, symptomatic PAD, or CKD to oral semaglutide or placebo. The primary outcome was 3-point MACE (CV death, nonfatal MI, and nonfatal stroke).
• Oral semaglutide was associated with a significant 14% relative reduction in MACE compared to placebo (HR 0.86 [95% CI: 0.77 – 0.96]), primarily driven by reduction in non-fatal MI. At 3 years, the absolute risk reduction with semaglutide was 2.0 percentage points, for number needed to treat of 50 persons. Serous adverse events were higher in the placebo group, but GI events were more common with semaglutide.
• Oral semaglutide is the first and only oral GLP-1 receptor agonist with proven CV benefits, demonstrating a risk reduction comparable to injectable GLP-1 agents, with no new safety signals identified.
   

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Key Points:

• A major limitation of antithrombotic therapy is the risk of bleeding if a patient requires urgent surgical or invasive procedures as well as the risk of spontaneous hemorrhage.
• Bentracimab is a first in class recombinant human immunoglobulin monoclonal antibody fragment that binds to ticagrelor and its active metabolite, rapidly neutralizing their antiplatelet effects.
• In this multi-center, phase 3 prospective, open-label, single-arm trial, bentracimab was shown to rapidly and effectively reverse ticagrelor in patients requiring urgent surgery or experiencing major bleeding, with high rates of hemostasis and favorable safety outcomes.

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Key Points:

• Patients with peripheral artery disease (PAD) in combination with type 2 diabetes (T2D) suffer from significant functional limitations and limited treatments.
• GLP-RA medications have demonstrated benefits that may target the pathobiology of PAD.
• In STRIDE, semaglutide was compared with placebo in patients with T2D and early symptomatic PAD.
• Semaglutide was associated with a significant improvement in maximum walking distance, pain free walking distance, quality of life, ankle brachial index, and disease progression.

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Key Points:

• Venous thromboembolism (VTE) is a leading cause of mortality in cancer patients
• Extended anticoagulation is recommended for cancer patients with VTE, but balancing efficacy and bleeding risk remains a challenge.
• The API-CAT trial demonstrated that extended reduced-dose apixaban (2.5 mg twice daily) was non-inferior to full-dose apixaban (5 mg twice daily) in preventing VTE recurrence while significantly lowering bleeding risk.

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Key Points: 

• In the WARRIOR trial, ~ 2500 women with signs and symptoms of ischemia without obstructive coronary disease (INOCA) were randomized to receive intensive medical therapy for coronary artery disease vs. continued usual care

• At five years, there was no significant difference in the rate of first occurrence of a major adverse cardiac event between the intensive medical therapy and control arms

• Important limitations of the trial include under-enrollment due to the COVID-19 pandemic and higher than anticipated rates of contamination of therapies due to the pragmatic trial design

According to a 2017 report from the Cardiovascular Disease in Women Committee of the American College of Cardiology, at least 3-4 million men and women in the United States have ischemia without obstructive coronary disease (INOCA), a syndrome that is defined by the presence of signs and symptoms of cardiac ischemia with no significant epicardial coronary disease (≥ 50% stenosis). Women are significantly more likely to have INOCA than men, and although there are no specific guidelines on the appropriate management of INOCA, there is growing evidence that INOCA is associated with higher rates of major adverse cardiac events (MACE). 

The Women’s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD was a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs usual care (UC) conducted in 4,422 symptomatic women with INOCA (NCT03417388) across approximately 70 United States sites. The hypothesis was that IMT will reduce the primary outcome of the first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes included quality of life, time to return to “duty”/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilized web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients’ homes to reduce site and patient burden. A biorepository was used to collect blood samples to assess potential mechanisms.

In the WARRIOR study, 2476 women from 71 centers across the United States who were found to have INOCA based on coronary angiography (n=1353) or coronary computed tomography angiography (n=1123) were randomized to receive intensive medical therapy versus ongoing usual care and followed every six months for the development of MACE including death, non-fatal myocardial infarction, non-fatal stroke or transient ischemic attack or hospitalization for heart failure or angina. In the intensive medical therapy arm, patients received low-dose aspirin, statin and an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). The average age of the population was 64 years old and ~ 89% of women were white. The sample included high representation of some risk factors for coronary disease including ~64% with hypertension, ~ 53% with obesity and ~37% with a history of tobacco use but only ~21% of patients had diabetes. 

At five years, there was no difference in the composite primary outcome of MACE between the two arms with an event rate of ~16% in both arms and a hazard ratio of 1.13 (95% CI: 0.94-1.37, p=0.20). There was no notable heterogeneity in the treatment effect for the primary outcome when evaluating subgroups of individual risk factors for coronary disease or subgroups of medication types. 

One of the most important limitations of the study is the high rate of contamination between the two treatment arms; approximately half the patients enrolled in the usual care arm were ultimately started on many of the medications included in the intensive medical therapy arm. In addition, 70% of patients were already taking statins at baseline and half were already on an ACE/ARB, further limiting the ability to detect a treatment effect between the two arms. Another notable limitation is that because the trial enrolled during the COVID-19 pandemic, there was significant under-enrollment leading to inability to achieve the target enrollment of 4,476 patients. Finally, because the population was primarily non-Hispanic white and post-menopausal, the results may not be generalizable to the broader population with INOCA. In conclusion, although the WARRIOR study did not show a benefit to intensive medication therapy compared to usual care, the findings of the study are not fully definitive or generalizable to the broader population. Future studies are needed to further understand the increased risk of MACE associated with INOCA and the best strategies to mitigate it. 

Key Points:

• Left ventricular thrombus (LVT) is a serious complication following heart attacks, particularly STEMIs, and can lead to systemic embolism or stroke.
• Warfarin has traditionally been the recommended therapy for treating LVT in patients post-STEMI.
• The RIVAWAR trial demonstrated that rivaroxaban was comparable to warfarin in achieving clot resolution at three months, providing a safer, more convenient alternative without the need for regular blood tests.

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