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ACC 2024 April 6-8, 2024

by | Oct 21, 2024 | Conference Update | 0 comments

CSL 112 (Apolipoprotein A-I) Infusions and Cardiovascular Outcomes in Patients with Acute Myocardial Infarction (ApoA-I Event ReducinG in Ischemic Syndromes II (AEGIS-II) Trial)

Gibson C, presented a session held at the American College of Cardiology (ACC) on 6th April 2024, in Atlanta, GA. The speaker and his team hypothesized that improving HDL function by infusing human ApoA-1, the primary functional component of HDL, would improve outcomes and reduce the risk of recurrent cardiovascular (CV) events after AMI.

  • An international, multicenter, randomized, double-blind, placebo-controlled trial was conducted involving 18,231 AMI patients with multivessel coronary artery disease and additional CV risk factors.
  • Patients were randomized to receive either 4 weekly infusions of apoA-I (6g CSL112) or placebo, with the first infusion administered within 5 days of first medical contact for the AMI.
  • The primary efficacy outcome was the time to first occurrence of the composite of CV death, MI, or stroke through 90 days.
  • Key secondary efficacy outcomes included the total number of hospitalizations for coronary, cerebral, or peripheral ischemia from the time of randomization through 90 days, and time to first occurrence of the composite of CV death, MI, or stroke from the time of randomization through 180 days and through 365 days.
  • The hypothesis of the AEGIS 2 Trial was CSL 112 ApoA-1 infusions improved cholesterol efflux in the setting of MI and reduced fat and macrophage content in atherosclerotic plaque. CSL 112 infusion will improve CV outcomes in the setting of MI. There were no imbalances in all hypersensitivity events (serious and non-serious).
  • The number of immune system disorder events (e.g. hypersensitivity or anaphylactoid reactions) leading to discontinuation from investigational product were low but were higher in the CSL112 group compared with the placebo group (14 vs 4 events, p=0.02).
  • There were fewer acute kidney injury events in the CSL112 arm (defined by changes in creatinine through the active treatment period): 570 (6.3%) vs 650 (7.2%) (p=0.02).
  • There were no significant imbalances in potential hepatic injury events (defined as ALT >3x ULN with Tbili >2x ULN or ALT >5x ULN), or new or worsening heart failure events (based on adjudication).

In AMI patients with multivessel disease and additional cardiovascular risk factors on standard therapies, CSL112 infusions did not significantly reduce CV death, MI, or stroke compared to placebo over 90 days. There was consistency in the primary endpoint in prespecified subgroups. The drug was well tolerated.

 

A Double-blind, Randomized Placebo-Procedure-Controlled Trial of an Interatrial Shunt in Patients with HFrEF and HFpEF: Principal Results from the RELIEVE-HF Trial

Stone G, presented a session held at the American College of Cardiology (ACC) on 6th April 2024, at Atlanta, GA that determined the safety and effectiveness of the V-Wave Ventura IAS device in symptomatic HF patients with any LVEF in a randomised, double-blind, placebo-procedure-controlled, multicentre trial.

  • In preclinical models and human pilot studies the Ventura 5.1-mm interatrial shunt (V-Wave Medical) has been shown to decompress the LA, with greater effect as LAP rises, an autoregulatory mechanism that may improve patient symptoms and prognosis.
  • The RELIEVE-HF trial is the pivotal IDE approval study for the Ventura shunt. HF patients with any LVEF who remained symptomatic (NYHA classes II, III or ambulatory IV) despite maximally tolerated class I HF treatments with a 6-min walk distance (6MWD) ≥100-≤450 meters were randomized 1:1 to transcatheter placement of the Ventura shunt or a placebo procedure.
  • Patients and all health care assessors remained blinded through 2-yr follow-up or until the last enrolled patient reached 1-yr follow-up.
  • The primary effectiveness endpoint is the hierarchical composite ranking of all-cause death, heart transplant or LVAD, recurrent HF hospitalizations, out-patient worsening HF events, and change in KCCQ-OS, reported as the WIN ratio.
  • The primary safety endpoint is device-related major adverse cardiovascular and neurologic events (MACNE) at 30 days.
  • Mean LVEF was 45.0%; 205 patients (40.4%) had HFrEF (LVEF <40%) and 303 (59.6%) had HFpEF. Baseline mean PCWP was 16.6 mmHg, mean RAP was 9.3 mmHg and mean PVR was 2.3 Wood units.

Transcatheter implantation of the Ventura inter-atrial shunt was safe but did not reduce symptoms or improve prognosis through 2 years in patients with HF across the full range of all LVEF. The results from a pre-specified stratified analysis suggest that inter-atrial shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF.

 

Empagliflozin After Acute Myocardial Infarction: Results of the EMPACT-MI Trial

Butler J, presented a session held at the American College of Cardiology (ACC) on 6th April 2024, at Atlanta, GA that evaluated the safety and efficacy of Empagliflozin in patients who have had acute myocardial infarction.

  • Despite advances in AMI management, post-MI patients remain at risk for developing HF upto 30% over the first year. The prognosis is especially poor in patients who develop congestion or left ventricular dysfunction with AMI.
  • SGLT2 inhibitors have been consistently shown to reduce the risk of HF events. The EMPACT-MI is a double-blind, randomized, placebo-controlled trial, that randomized 6522 patients with AMI to receive empagliflozin 10 mg once daily or placebo, in addition to standard of care.
  • Patients were eligible if they had no prior HF, were hospitalized with an AMI and had signs or symptoms of congestion requiring treatment and/or a newly depressed LVEF <45%. Patients were also required to have ≥1 additional HF risk factor.
  • The primary outcome was time to first HHF or all-cause death. A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo.
  • During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21).
  • With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio,0.96; 95% CI, 0.78 to 1.19).

Empagliflozin did not significantly reduce the risk of time to first HHF or all-cause death following AMI Empagliflozin demonstrated 23% and 33% relative risk reduction of first HHF* [*HR 0.77 (95% CI: 0.60, 0.98).] and total HHF, † [†RR 0.67 (95% CI: 0.51, 0.89).] components of the primary and first key secondary endpoints respectively. The risk reduction for HHF was consistent in subgroup and sensitivity analyses. The safety was consistent with the known safety profile of Empagliflozin.

 

Relationship Between Major Bleeding Events and Chronic Kidney Disease in Patients Undergoing Percutaneous Coronary Intervention

Iyer M, et al. presented a study in a session held at the American College of Cardiology (ACC) on 6th April 2024 in Atlanta, GA highlighting a lack of detailed description regarding the relationship between chronic kidney disease (CKD) and the frequency and types of major bleeding events following percutaneous coronary intervention (PCI).

  • The study included patients who underwent PCI between 2009 and 2017, identified from the institute’s National Cardiovascular Disease Registry (NCDR) CathPCI Database. Patients were divided into different groups based on their chronic kidney disease (CKD) stage, including Stage 1 (eGFR≥90%), Stage 2 (eGFR 60-89%), Stage 3a (eGFR 45-59%), Stage 3b (eGFR 30-44%), Stage 4 (eGFR 15-29%), Stage 5 (≤15%), and those currently undergoing dialysis.
  • The main focus was on major in-hospital bleeding events, defined according to NCDR criteria. These events were further analysed using multivariable logistic regression, taking into account the source of bleeding.
  • The study reported that among 13,537 patients who underwent PCI, there were 817 bleeding events, accounting for 6.0% of cases. The rates of total major bleeding, blood transfusion, gastrointestinal/genitourinary (GI/GU) bleeding, access site hematoma, and asymptomatic drops in hemoglobin ≥ 3 g/dL increased incrementally across CKD Stages 1-5 (P<0.05 for all types), as depicted in the figure.
  • Even after adjusting for multiple variables, CKD Stages 3a, 3b, 4, and dialysis remained as independent predictors of major bleeding following PCI (P<0.05 for all), as illustrated in the figure.

The degree of baseline CKD is a robust and independent predictor of heightened risk for major bleeding events post PCI, including the need for blood transfusion, occurrences of GI/GU bleeding, access site hematoma, and asymptomatic drops in hemoglobin.

 

Plozasiran (ARO-APOC3), An Investigational RNAi Therapeutic, Demonstrates Profound and Durable Reductions in APOC-3 and Triglycerides (TG) in Patients with Severe Hypertriglyceridemia (SHTG), SHASTA-2 Final Results

Gaudet D presented the session held at the American College of Cardiology (ACC) on 7th April 2024, in Atlanta, GA, that discussed the SHASTA-2 trial results.

  • Individuals with severe hypertriglyceridemia have an increased acute pancreatitis (AP) risk. Current treatments fail to lower TGs below a threshold that exposes patients to the risk of AP.
  • Plozasiran, a hepatocyte targeted siRNA reduces circulating TGs by interfering with the production of APOC3, a key regulator of TG metabolism. SHASTA-2, a randomized, placebo-controlled, Phase 2b study (NCT04720534) evaluated efficacy and safety of plozasiran in patients with SHTG.
  • Eligible patients (n=229) randomized 3:1, received a total of 2 doses (SQ 10, 25, or 50 mg plozasiran) or matched placebo on Day 1 and at Wk12 and followed through Wk48.
  • The primary endpoint was percent change from baseline in fasting TGs at Wk24. Mixed model repeated measure (MMRM) approaches were used for statistical modelling.
  • Plozasiran decreases LS mean serum APOC3, TGs, and remnant cholesterol while increasing HDL-C at 24 weeks (persisting at 48 weeks) for all dose levels: APOC3 lowered to -78%, (-48%); TG lowered to -74%, (-58%), Remnant cholesterol lowered to -62%, (-45%); HDL-C increased up to +68%, (+38%).
  • Over 90% of subjects at 24 weeks treated with Plozasiran achieved TGs <500 mg/dL and below the risk threshold for Acute Pancreatitis.
  • Plozasiran has a favorable safety profile at 48 weeks. These data support further development of plozasiran in planned phase 3 programs for the treatment of chylomicronemia and SHTG.
  • Based on these results, RNAi-mediated silencing of hepatic APOC3 expression via plozasiran is a promising potential treatment for subjects with SHTG.

Plozasiran produced highly durable TG reductions below the threshold associated with elevated AP risk. Key atherogenic lipoprotein parameters also improved. The safety profile was favorable at all doses. These data support initiation of pivotal studies of Plozasiran for the treatment of SHTG.

 

Effect of Gamification, Financial Incentives, or Both Combined to Increase Physical Activity Among Patients with Elevated Risk for Major Adverse Cardiovascular Events. The Be Active Randomized Clinical Trial

Fanaroff A, presented the session held at the American College of Cardiology (ACC) on 7th April 2024, in Atlanta, GA, that determined the effectiveness of behaviourally-designed gamification, loss-framed financial incentives, or the combination versus control for increasing physical activity over a 12-month intervention and 6-month follow-up period.

  • Consensus guidelines recommend that individuals with or at risk for atherosclerotic cardiovascular disease (ASCVD) participate in regular physical activity, but most do not do so.
  • Concepts from behavioural economics have been used to design interventions that increase physical activity over shorter periods, but longer-term effectiveness is uncertain.
  • All randomly assigned patients were included in the intention-to-treat analysis: multiple imputation for days with missing step count or values < 1000, sensitivity analyses using only captured data without imputation, generalized linear mixed effect regression models to evaluate changes from baseline in daily steps and minutes of MVPA, powered to compare all 3 interventions vs. control using Bonferroni adjustment of type 1 error rate with two-sided α = 0.017, intervention arms significant versus control were compared with each other, with same adjustment of type 1 error rate, 93% power to detect a difference of 1000 steps and 85% power to detect a difference of 750 steps.
  • Among 1062 randomized participants, mean (SD) age was 67 (8) years, 60% were female, and 25% are Black. Mean (SD) baseline daily step count was 5030 (1599).
  • In observational studies, there is an inverse association between steps per day and outcomes (mortality, CV events). These highly scalable, automatically delivered interventions increase physical activity over long-term periods in patients at high risk for CV events and could improve outcomes.

BE ACTIVE, the largest and longest-duration trial of strategies to increase physical activity, will identify whether strategies informed by behavioural economic theory promote sustained increases in physical activity in individuals with or at risk for ASCVD.

 

Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: A Phase 3 Randomized, Open Label, Blinded Endpoint, Superiority Trial of Enalapril to Prevent Anthracycline-induced Cardiotoxicity (PROACT)

Austin D, presented a session held at the American College of Cardiology (ACC) on 8th April 2024, in Atlanta, GA that evaluated the effectiveness of Enalapril in preventing cardiotoxicity in patients receiving high dose anthracyclines (>300mg/m2 epirubicin-equivalent) to treat Breast Cancer or Non Hodgkin lymphoma.

A prospective, multi-center, randomized, blinded end-point, superiority trial of 111 patients at 13 UK sites. Adults with Breast cancer or Non-Hodgkin lymphoma planned to receive 6 cycles of anthracycline chemotherapy, with a negative baseline troponin T, consented. Patients were randomized to no Enalapril or Enalapril titrated to 10mg BD; chemotherapy regimen was a minimisation factor.

  • The primary outcome was presence or absence of cardiac troponin T release (measured as presence (≥14ng/L)) during anthracycline treatment, and one month after the last anthracycline dose.
  • Secondary outcomes include troponin I, LV ejection fraction, and LV global longitudinal strain.
  • 81% of patients had myocardial injury on cardiac troponin T criteria
  • 46% of patients had myocardial injury on cardiac troponin I criteria
  • 21% had a >15% relative decrease in LV GLS (Left Ventricular Global Longitudinal Strain)
  • 2% had a >10% reduction in LV EF (left ventricular ejection freaction) to <50%
  • Enalapril did not affect myocardial injury or cardiac function outcomes

Adding Enalapril to standard care was not superior to standard care alone in the prevention of cardiotoxicity in patients receiving high-dose anthracycline based chemotherapy.

 

Remnant Lipoprotein Cholesterol Levels, Intensive Blood Pressure Treatment, and Cardiovascular Outcomes: Insights from the SRINT Trial

Gabani M.H presented a session held at the American College of Cardiology (ACC) on 8th April 2024, in Atlanta, GA that discussed the insights of SPRINT trial which examined the association of remnant lipoprotein cholesterol (RLP-C) and hypertension (HTN) management strategies with cardiovascular (CV) outcomes.

  • The SPRINT study explored the benefits of intensive blood pressure (BP) control in hypertensives without diabetes.
  • Among 9361 participants, SBP targets were at <140 mm Hg (standard) or <120 mm Hg (intensive).
  • Four groups based on RLP-C and treatment strategy: Group 1 (RLP-C < median, intensive), Group 2 (RLP-C > median, intensive), Group 3 (RLP-C < median, standard), and Group 4 (RLP-C > median, standard). RLP-C calculated as RLP-C=TC−HDL-C−LDL-C.
  • The primary outcome is a composite of MI, ACS, stroke, HF, and CV death. Median follow-up is 3.26 years.
  • Kaplan-Meier analysis showed significant differences between groups (log-rank p < 0.0001). Group 1 had 91 events (4.16%), Group 2 150 events (6.17%), Group 3 128 events (5.84%), and Group 4 had 184 events (7.60%).
  • Hazard ratios (HR, 95% CI) determined using Cox regression, adjusting for age, race, sex, smoking, BMI, statins, and fasting glucose. Compared to Group 1, HR for Group 2 (HR=1.64, 1.25-2.14, p=0.0003), Group 3 (HR=1.43, 1.08-1.88, p=0.0101), and Group 4 (HR=2.05, 1.58-2.65, p<.0001).
  • No interaction of management strategy and RLP-C on the primary outcome was observed.

Elevated RLP-C is associated with adverse CV outcomes, especially with standard BP treatment. RLP-C may serve as a prognostic biomarker for personalized BP management.

 

Efficacy and Safety of Fixed Dose Combination Therapy of Low Intensity Rosuvastatin and Ezetimibe in Hypercholesterolemia Patients

Yang In-Ho presented a session held at the American College of Cardiology (ACC) on 8th April 2024, in Atlanta, GA that compared the safety and efficacy of the combination therapy of low intensity rosuvastatin and ezetimibe with moderate intensity rosuvastatin monotherapy in patients with hypercholesterolemia.

  • This was a randomized, double-blind, multicenter study conducted at 30 medical centers in South Korea.
  • 314 patients who fulfil the inclusion criteria were randomly assigned in one of four groups after 4 to 6 weeks of run-in period: fixed dose combination of rosuvastatin 2.5mg and ezetimibe 10mg; rosuvastatin 2.5mg; ezetimibe 10mg; and rosuvastatin 5mg.
  • The primary end point was the percentage change of serum low-density lipoprotein cholesterol (LDL-C) level after 8 weeks of drug treatment.
  • After treatment period, significant decrease of serum LDL-C level at week 8 was noted in rosuvastatin 2.5mg group than in ezetimibe 10mg group (rosuvastatin 2.5mg group -30.9±3.2%; ezetimibe 10mg group -16.4±3.4%).
  • The proportion of patients who achieved target LDL-C level was significantly higher in the rosuvastatin 2.5mg/ezetimibe 10mg group than any other group, including rosuvastatin 5mg group (rosuvastatin 2.5mg/ezetimibe 10mg group 70.1%; rosuvastatin 2.5mg group 39.0%; ezetimibe group 18.2%; rosuvastatin 5mg group 50.0%).

The combination of low-intensity rosuvastatin and ezetimibe showed a greater decrement of serum LDL-C level when compared with moderate-intensity rosuvastatin, with good tolerance considering adverse events.

 

Understanding the Importance of Age in Selecting a Testing Strategy for Stable Symptomatic Patients with Suspected Coronary Artery Disease: A Prespecified Analysis from the PRECISE Randomized Trial

Vemmou E, et al. presented a study in a session held at the American College of Cardiology (ACC) on 8th April 2024 in Atlanta, GA.

  • In PRECISE, a precision evaluation with risk stratification and coronary computed tomography angiography (CTA) with FFR (CTA±FFR) was superior to usual testing for the primary endpoint of death, MI, or catheterization (cath) without obstructive coronary artery disease (CAD) at 1 year.
  • The impact of age on 1) the primary endpoint for the entire cohort, and 2) on diagnostic performance for obstructive CAD in an intermediate risk subset excluding lowest and highest risk deciles was assessed.
  • In both younger (N=1430) and older patients (N=673), the rates of the primary endpoint were lower with a precision evaluation compared to usual care (<65: 2.7% vs. 8.7%; >65: 7.5% vs. 16.4%; p interaction=0.32).
  • Within the intermediate-risk subset (n=1140), a positive CTA result was linked to catheterization revealing obstructive CAD in most patients across both age groups.
  • In contrast, a positive stress test was associated with low rates of obstructive CAD in both age groups (26.1% in <65, 9.1% in >65).
  • The adjusted association between test positivity and obstructive CAD on Cath favored CTA±FFR over stress testing in both age groups (<65 HR 2.76 (1.45, 5.25); >65, HR 4.89 (1.07,22.36)).

In the PRECISE study, CTA±FFR demonstrated superior performance compared to conventional testing for both younger and older patients. Among intermediate-risk patients, stress testing exhibited subpar performance in identifying individuals with obstructive CAD in both age groups, particularly those aged 65 and above.