AHA 2024
Zerlasiran Was Well Tolerated and Reduced Time-averaged Lp(a) Concentration: The ALPACAR Trial
Key Takeaways:
- Zerlasiran, a short interfering RNA (siRNA) targeting lipoprotein(a) (Lp(a)), was well tolerated and led to significant reductions in Lp(a) serum concentrations in both healthy participants and patients with stable atherosclerotic cardiovascular disease (ASCVD).
- A single dose of 600 mg of zerlasiran resulted in a maximal median reduction of Lp(a) by 99%, with 90% and 89% reductions sustained at 201 days for the 300 mg and 450 mg doses, respectively.
- The study found no serious adverse events, with mild to moderate injection site reactions being the most common side effect. Elevations in C-reactive protein were transient and resolved by day 7.
AMULET IDE Trial 5 years Showed Long-term Safety and Efficacy of AMPLATZER Amulet and Watchman Device in LAAO
Key Takeaways:
- The AMULET IDE trial compared the AMPLATZER Amulet occluder with the Watchman 2.5 device in patients with nonvalvular atrial fibrillation (NVAF) at high risk of thromboembolism.
- Patients with the Amulet occluder were significantly more likely to be free from oral anticoagulation (OAC) at 5 years compared with the Watchman device (94.0% vs. 90.9%, p = 0.009) and clinical outcomes, including rates of ischemic stroke or systemic embolism (7.4% vs. 7.1%, p = 0.851) and major bleeding (20.1% vs. 20.0%, p = 0.882), were similar between the devices.
- Strokes in the Amulet occluder group were less often fatal or disabling compared to the Watchman group (22 vs. 39 events, p = 0.030).
ATTR-Specific Medication and AVR Improve Survival in Patients with Aortic Stenosis and ATTR Cardiac Amyloidosis
Key Takeaways:
- In this international registry, 266 patients with dual pathology, aortic stenosis and cardiac amyloidosis were identified and matched. A control cohort of lone AS receiving aortic valve replacement was used for outcome comparison.
- ATTR-specific medication, predominantly tafamidis, significantly improved survival in patients with dual aortic stenosis (AS) and transthyretin-associated cardiac amyloidosis (ATTR-CA) (adjusted HR 0.42; 95% CI 0.24–0.72), emphasizing its role in managing this complex pathology.
- Aortic valve replacement (AVR), particularly in severe AS, provided substantial survival benefits (HR 0.42; 95% CI 0.25–0.72), with the combination of AVR and ATTR-specific therapy yielding outcomes comparable to lone AS patients undergoing AVR.
Bempedoic Acid Reduces Major Adverse Limb Events in Patients with PAD : A Pre-specified Analysis from the CLEAR Outcomes Trial
Key Points:
- Patients with peripheral artery disease (PAD) at an increased risk of both major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs)
- Bempedoic acid is thought to reduce MACEs in primary and secondary prevention patients, but it is unknown whether the same can be said for MALEs
- The CLEAR Outcomes trial randomized patients to either bempedoic acid versus placebo to determine rates of MALEs, and some rates of MACEs, among at risk patients and patients diagnosed with PAD
- The study showed significant reduction in MALEs for all patients and patients with diagnosed PAD, as well as reduction in composite MACEs and MALEs, suggesting a possible role for bempedoic acid in PAD treatment and prevention
Consistent Efficacy and Safety of Finerenone in Women and Men: A Secondary Analysis of the FINEARTS-HF Trial
KEY POINTS:
- Historically women have been underrepresented in cardiovascular clinical trials, however, rates of Heart Failure with Preserved Ejection Fraction are rising more rapidly in women
- FINEARTS-HF trial enrolled 46% of female participants and demonstrated a reduction in heart failure exacerbations in both sexes with the use of finerenone, compared to placebo
Oral Muvalaplin Lowered Lipoprotein(a): The KRAKEN Trial
Key Takeaways:
- KRAKEN was an international, multicenter, placebo controlled, phase 2 trial that tested the effects of muvalaplin at different doses—10 mg, 60 mg or 240 mg, taken daily—vs placebo for 12 weeks.
- Muvalaplin reduced Lp(a) levels by up to 85.8% at the highest dose (240 mg/day), with 96.7% of participants in this group achieving Lp(a) levels below 125 nmol/L.
- The safety profile of muvalaplin was favorable, with mild to moderate gastrointestinal events being the most common side effects and no significant concerns regarding liver function or systemic inflammation markers.
- Muvalaplin represents a significant advancement in addressing elevated Lp(a) levels, offering a potential oral treatment option that could reduce cardiovascular risk in individuals with high Lp(a) concentrations.
Rivaroxaban for 18 Months Superior to 6 Months To Prevent Recurrent VTE Events in Cancer Patients with Acute-low PE: ONCO PR
Key Takeaways:
- The ONCO PE trial demonstrated that an 18-month treatment with rivaroxaban significantly reduced recurrent venous thromboembolism (VTE) compared to a 6-month treatment in patients with cancer and acute low-risk pulmonary embolism (PE) (5.6% vs. 19.1%; OR, 0.25; 95% CI, 0.09–0.72; P=0.01).
- There was no statistically significant increase in major bleeding events with the longer rivaroxaban treatment (7.8% vs. 5.6%; OR, 1.43; 95% CI, 0.44–4.70; P=0.55).
- The study highlights the benefits of extended anticoagulation in preventing thrombotic events in this patient population, though individual bleeding risks must be considered.
Promising Cardioprotective Effect of ARNi in High-Risk Cancer Patients Treated with Anthracycline Chemotherapy: SARAH
Key Points:
- Anthracycline (ANT)-based chemotherapy is a known cancer treatment regimen but results in cardiotoxicity secondary to heart failure
- The SARAH trial explored whether the angiotensin receptor-neprilysin inhibitor (ARNi), sacubitril/valsartan, might be cardioprotective against heart failure among high-risk patients receiving ANT therapy
- The study investigated treatment with ARNI versus placebo for 6 months to determine the incidence of worsened global longitudinal strain (GLS) in the left ventricle (LV) as well as other secondary outcomes
- The SARAH trial found lower rates of worsened GLS as well as improved GLS in the ARNi group compared to the control group, raising questions about the benefits of ARNi for prevention of cardiotoxicity in high-risk patients
Semaglutide Improves CV Outcomes in Patients with Prior Coronary Artery Bypass Surgery: Insights from the SELECT Trial
Key Takeaways:
- In this secondary analysis of the SELECT Trial, semaglutide 2.4 mg once weekly significantly reduced the risk of major adverse cardiovascular events (MACE) in patients with or without a history of coronary artery bypass grafting (CABG), with a greater absolute risk reduction observed in the CABG group (2.3% vs. 1.0%).
- Patients with prior CABG, who were at higher baseline cardiovascular risk, experienced fewer serious adverse events with semaglutide (38%) compared to placebo (44%), reinforcing its efficacy and safety in this high-risk subgroup.
VALOR-HCM: Mavacamten Reduces Long-Term Need for Septal Reduction Therapy in Symptomatic Obstructive HCM
Key Points:
- In patients with treatment-refractory symptomatic obstructive hypertrophic cardiomyopathy (HCM), invasive septal reduction therapies (SRT)—alcohol septal ablation or surgical myectomy—are often the last resort for symptom management. Septal reduction therapies are limited in availability and associated with procedural risks.
- The VALOR-HCM trial demonstrated that mavacamten significantly reduced the need for SRT in severely symptomatic HCM patients at 16, 32, and 56 weeks.
- At 128 weeks, mavacamten provided sustained freedom from SRT, with nearly 90% of patients remaining on long-term therapy.
FLOW Trial: Renal Benefits of Semaglutide in T2DM Similar Regardless of Baseline CV Risk
Key Points
- Both chronic kidney disease (CKD) and cardiovascular disease (CVD) are prevalent in type 2 diabetes (T2DM), contributing to morbidity and mortality.
- The FLOW trial demonstrated that semaglutide, a GLP-1 receptor agonist, was associated with a 24% relative risk reduction in the primary composite kidney outcome compared to placebo among those with T2DM.
- This analysis stratified by baseline CVD status and CVD risk, and found consistent renal benefits across these subgroups without evidence of a heterogeneous treatment effect.
CKD and CVD are leading causes of death and disability in patients with T2DM. Both conditions often coexist, increasing the risk of adverse outcomes. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in improving glycemic control and reducing the risk of CV events, but its effects on CKD outcomes, particularly in subgroups defined by CVD risk, are less well understood.
On November 18th 2024, findings from “Benefits of Semaglutide on Chronic Kidney Disease Outcomes by Cardiovascular Status or Risk in the FLOW trial” were presented at AHA Scientific Sessions 2024.
The FLOW trial was a phase 3, double-blind, randomized controlled study designed to assess the effects of semaglutide on CKD progression in patients with type 2 diabetes. The study included 3,533 participants with type 2 diabetes and CKD, who were randomized to receive weekly subcutaneous semaglutide 1.0 mg or placebo. Participants met one of two inclusion criteria: eGFR 50–75 mL/min/1.73 m² with a urine albumin creatinine ratio (UACR) >300 to <5,000 mg/g, or eGFR 25–<50 mL/min/1.73 m² with a UACR >100 to <5,000 mg/g. Patients were followed for a median of 3.4 years. The trial’s primary endpoint was a composite of kidney failure (eGFR <15 mL/min/1.73 m², dialysis, or transplant), ≥50% eGFR decline from baseline, and kidney or CV death. This pre-specified subgroup analyses stratified the participants by prior cardiovascular events or CVD risk, including myocardial infarction (MI), stroke, peripheral artery disease (PAD) in those with baseline CVD, and CVD risk estimated using the PREVENT score in those without baseline CVD (categorized into <20% or ≥ 20%).
At baseline, participants had a mean age of 67 years, 30% were female, mean eGFR was 47 mL/min/1.73 m², and median UACR was 568 mg/g. In the overall population, semaglutide reduced the relative risk of the composite kidney outcome by 24% compared to placebo (HR: 0.76; 95% CI: 0.66–0.88). Annual eGFR decline was also slower with semaglutide. Benefits were consistent across all CVD and CV risk subgroups. Among those with prior MI, stroke, or PAD, hazard ratios ranged from 0.72 to 0.95, showing no significant heterogeneity. Patients with higher baseline CV risk (PREVENT score ≥20%) experienced similar reductions in kidney outcomes (HR: 0.73; 95% CI: 0.58–0.91) compared to those with lower risk scores (HR: 0.73; 95% CI: 0.49–1.08).
These FLOW trial results demonstrate that semaglutide provides substantial benefits in slowing CKD progression and reducing kidney failure in type 2 diabetes, regardless of cardiovascular status or risk. The findings underscore the broad applicability of semaglutide in managing the dual burden of diabetes and CKD.
Reconditioned Pacemakers Non-Inferior To New Pacemakers in Low- and Middle-Income Countries: Preliminary Results from My Heart Your Heart Trial
Key Points:
- Many patients in low- and middle-Income countries are unable to obtain new pacemaker devices. It is unknown if reconditioned pacemakers are as effective as new pacemakers.
- In this randomized clinical trial, 298 patients who had class I indications for a pacemaker but no financial means to obtain one were given either a reconditioned pacemaker or a new pacemaker at implant.
- Reconditioned pacemakers was found to be non-inferior to new pacemakers for infection and lead complications at 90 days.
Linear Ablation Combined with EIVOM Provides Additional Benefit in Rhythm Outcomes for Persistent AF Ablation: PROMPT-AF Trial
Key Points:
- It is unknown if linear ablation with ethanol infusion of the vein of Marshall (EIVOM) in addition to pulmonary vein isolation (PVI) improves outcomes as compared to PVI alone in patients with persistent atrial fibrillation.
- In this investigator-initiated, open-label randomized clinical trial, 498 patients with persistent atrial fibrillation without a history of ablation were randomized in a 1:1 fashion.
- Linear ablation with EIVOM plus PVI was associated with freedom from atrial arrhythmia recurrence at 12 months compared to PVI alone.
Metformin and Aggressive Lifestyle Modifications Reduce AF Fibrillation Symptoms but Not Burden: Results From the TRIM-AF Trial
Key Points:
- Despite prior data suggesting decrease in metabolic stress may reduce atrial fibrillation (AF) progression, the effects of aggressive lifestyle and risk factor modifications (LRFM) or metformin on AF progression remain unknown.
- In this prospective, randomized, open-label clinical trial, 149 patients with atrial fibrillation and an implanted cardiac device capable of continuous AF monitoring were randomized to standard of care, metformin, LRFM or metformin + LRFM.
- Metformin, LRFM, or the combination did not reduce AF burden compared to standard of care although both LRFM arms reduced AF symptom scores.
SUMMIT Subanalysis: Tirzepatide Reduces Symptom Burden in Patients with Obesity-Related HFpEF
Key Points
- Patients with heart failure with preserved ejection fraction (HFpEF) and obesity often have significant functional limitations.
- The SUMMIT trial demonstrated that tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improved clinical outcomes, reduced symptom burden, and enhanced functional status in patients with HFpEF and obesity.
- These benefits were likely driven by reductions in cardiac filling pressures, volume overload, and heart failure medication requirements.
In a Hierarchical Composite Outcome, Finerenone Shows Reduction in HF Exacerbations in HFmrEF or HFpEF: FINEARTS
KEY POINTS:
- Hierarchical analysis prioritizing significant events more effectively traditional composite outcomes, offering clearer clinical guidance
- In a pre-specified analysis, using a win-ratio and win-odds approach, finerenone demonstrated a reduction in heart failure events compared to placebo
Finerenone Raises Potassium but Retains Clinical Benefits with Protocol-directed Surveillance and Dose Adjustment: FINEARTS
KEY POINTS:
- Finerenone, a non-steroidal mineralocorticoid (MRA), increased serum potassium levels more often than placebo. However, adverse events from hyperkalemia were rare
- The incidence of cardiovascular death or heart failure exacerbation was lower in patients using finerenone, even when serum potassium was elevated, as compared to use of the placebo group with a normal serum potassium
HELIOS-B trial – Vutrisiran Reduces Risk of Outpatient Worsening Heart Failure in ATTR-CM in a subgroup analysis
Key Points:
- Transthyretin amyloidosis (ATTR-CM) is a fatal disease caused by the deposition of misfolded amyloid protein in the heart, leading to heart failure and poor cardiovascular outcomes.
- In the HELIOS-B trial, vutrisiran, an RNA interference therapeutic, significantly reduced all-cause mortality and cardiovascular (CV) events in patients with ATTR-CM.
- This prespecified analysis showed that worsening heart failure (HF) portends worse outcomes, including all-cause mortality and CV events, among ATTR-CM patients.
- Vutrisiran significantly reduced the risk of outpatient worsening HF and the composite of all-cause mortality and recurrent CV events compared with placebo.
ARREST-AF: Aggressive Risk Factor Management After AF Ablation Reduces Arrythmia Recurrence at 12 Months
Key Points
- Observation data has suggested that improving cardiometabolic risk factors after AF ablation may reduce the recurrence of arrythmias.
- The ARREST-AF trial provides randomized controlled evidence demonstrating the benefits of a physician-led clinic focusing on risk factor modification (RFM) in reducing arrhythmia recurrence at 12 months.
- Patients in the RFM group were significantly more likely to be free from recurrent arrhythmia and experienced improved AF symptom scores compared to those receiving usual care.
- Improvements in body weight, systolic blood pressure, glycemic control, and exercise capacity were also observed in the RFM group, underscoring the role of risk factor control in mediating the observed benefits.
Prior observational studies have pointed to the role of aggressive risk factor modification (RFM) in improving long-term outcomes after catheter ablation for atrial fibrillation (AF). However, randomized controlled trial data to validate this hypothesis has been lacking.
On November 18th 2024, the results of “Aggressive Risk factor REduction STudy for Atrial Fibrillation (ARREST-AF) implications for ablation outcomes: A Randomized Clinical Trial” were presented at AHA Scientific Sessions 2024. The purpose of this study was to determine if attempts at intensive RFM after AF ablation improves outcomes.
This randomized controlled trial included 122 consecutive Australian adult patients with paroxysmal or persistent symptomatic AF undergoing catheter ablation (pulmonary vein isolation with additional ablation at operator discretion) who had a body mass index of ≥ 27 kg/m2 and one additional cardiometabolic risk factor. Patients with severe structural heart or systemic disease were excluded. They were assigned in a 1:1 fashion at to RFM or usual care arm. Patients in the RFM arm received intensive risk factor management through a physician-led clinic, following AHA guideline-based recommendations. Patients in the usual care arm received standard, guideline-directed care for AF management. The primary endpoint was proportion of patients free from AF recurrence 12 months post-ablation. Secondary endpoints included changes in AF symptom severity, cardiometabolic risk factors, exercise capacity and need for redo ablation.
At 12 months, 66% of patients in the RFM group were free from AF recurrence at 12 months, compared to 42% in the usual care group, a significant difference (HR 2.18 [95% CI 1.25-3.70]; p=0.004). In addition, AF symptom severity was significantly improved in the RFM group compared to the usual care group. The RFM group also had significantly improved body weight, glycemic control, and exercise capacity, indicating that the intervention was successful at achieving an improvement in control of major cardiometabolic risk factors.
Rajeev K. Pathak, MD, PhD, FACC, Director of Cardiac Electrophysiology at Canberra Heart Rhythm in Garran, Australia, concluded: “Amongst patients with AF, elevated BMI and one additional cardiometabolic risk factor, aggressive risk factor management reduces arrhythmia recurrence in the 12-months following catheter ablation when compared with usual care.”
SUMMIT CMR: Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related HFpEF
Key Points
- Obesity-related heart failure with preserved ejection fraction (HFpEF) is associated with increased left ventricular (LV) concentric remodeling and paracardiac adipose tissue (PAT), which may exacerbate HFpEF through systemic and myocardial inflammation.
- The cardiac magnetic resonance imaging (CMR) substudy of the SUMMIT trial demonstrated that tirzepatide, a dual GIP/GLP-1 receptor agonist, significantly reduces LV mass and PAT in patients with obesity-related HFpEF.
- Tirzepatide’s effects on cardiac structure and function correlated with weight loss and improvements in other clinical parameters, and may have contributed to its clinical efficacy in reducing heart failure events