Bird’s Eye View of the Trials Presented at ESC 2023: Part 2

In continuation of the previous part, the trials presented at ESC 2023 are hereby presented according to the area of interest of the studies. The trials (15) are presented followed by comments for each (A) Complete Revascularization 2 (MULTISTARS AMI, FIRE); (B) Antithrombotics 4 (OPT BRISK, STOP DAPT 3, SHARE, RIGHT); (C) Preventive Cardiology (1); (D) Inflammatory disease 1 (ARAMIS); (E) Cardiac arrest 2 (ARREST, ECLS SHOCK); (G) Valvular Heart Disease 1 (RIVER trial); (H) Cardio Oncology 1 (ONCO DVT); and (I) Pharmacotherapy 3 (LODESTAR, SGLT2 IN COVID 19, NITRATE CIN).

A. Complete Revascularization

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction

Stähli BE, Varbella F, Linke A, et al. Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2023;389(15):1368−1379.

Abstract

Background: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of non-culprit lesions should be performed remains unknown.

Methods: We performed an international, open-label, randomized, non-inferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion, followed by staged multivessel PCI of non-culprit lesions within 19–45 days after the index procedure (staged group). The primary endpoint was a composite of death from any cause, non-fatal myocardial infarction (MI), stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure 1 year after randomization. The percentages of patients with a primary or secondary endpoint event are provided as Kaplan–Meier estimates at 6 months and 1 year.

Results: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary endpoint event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval [CI], 0.38–0.72; P < .001 for non-inferiority and P < .001 for superiority). Non-fatal MI and unplanned ischemia-driven revascularization occurred in eight patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group, 22 patients (5.3%) and 39 patients (9.3%) in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event.

Conclusions: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was non-inferior to staged multivessel PCI concerning the risk of death from any cause, non-fatal MI, stroke, unplanned revascularization, or hospitalization for heart failure at 1 year.

Comments: Approximately, more than half of the patients with acute MI have a lesion in the non-infarcted artery. Complete revascularization is beneficial, based on the recent COMPLETE trial. Whether the revascularization is to be done immediately or during the index hospitalization or staged procedure in follow-up is a matter of debate. This trial was undertaken to address this. The immediate multivessel PCI was non-inferior to the staged procedure in terms of outcomes. The benefit was driven by the reduction in non-fatal MI and ischemic-driven target lesion revascularization during follow-up. Two schools of thought come into debate on complete revascularization, and each has their valid explanations. One is that immediate revascularization is beneficial, as all the coronaries are exposed to the same stress and the lesions might be unstable even when non-significant (as evident by intravascular ultrasound studies). Stenting those lesions would reduce the future major adverse cardiovascular events. This cannot be generalized to all the people. The non-infarct-related artery might be calcified, tortuous, distal to the stent, and can have in-stent restenosis. Chasing these lesions might be harmful rather than beneficial. A staged procedure is the preferred option in such scenarios (after 6 weeks, completion of acute phase) the second school of thought. The composite endpoints in terms of efficiency of a procedure is well known, but there is a danger of oversimplifying the evidence. Here the question arises whether the complete revascularization has a significant impact on individual components than combinedly. Finally, to conclude immediate complete revascularization is beneficial in acute coronary syndrome (ACS) provided the non-infarct arteries are straightforward to address.

Complete or Culprit-only PCI in Older Patients with Myocardial Infarction

Biscaglia S, Guiducci V, Escaned J, et al. Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction. N Engl J Med. 2023;389(10):889−898.

Abstract

Background: The benefit of complete revascularization in older patients (≥75 years of age) with MI and multivessel disease remains unclear.

Methods: In this multicenter, randomized trial, we assigned older patients with MI and multivessel disease who were undergoing PCI of the culprit lesion to receive either physiology-guided complete revascularization of non-culprit lesions or to receive no further revascularization. Functionally significant non-culprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, MI, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or MI. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding.

Results: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77–84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation MI. A primary-outcome event occurred in 113 patients (15.7%) in the complete revascularization group and 152 patients (21.0%) in the culprit-only group (hazard ratio [HR], 0.73; 95% CI, 0.57–0.93; P = .01). Cardiovascular death or MI occurred in 64 patients (8.9%) in the complete revascularization group and 98 patients (13.5%) in the culprit-only group (HR, 0.64; 95% CI, 0.47–0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = .37).

Conclusions: Among patients who were 75 years of age or older with MI and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, MI, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI.

Comments: The previous trial was angiography-based complete revascularization, and the present trial is physiology-guided complete revascularization. It was efficacious in elderly people with acute MI and multivessel disease. The benefit was driven by the reduction in deaths and MI. The most appropriate revascularization strategy (immediate, in-hospital, or staged) might be known in the ongoing trials. Shared decision-making is to be considered on an individual basis when addressing this population.

B. Antithrombotics (Antiplatelets and Anticoagulants)

OPT BIRISK (Optimal antiplatelet Therapy for high Bleeding and Ischemic RISK patients)

Professor Y. Han. Extended clopidogrel monotherapy versus DAPT in high-risk patients: the OPT-BIRISK trial Presented at European Society of Cardiology Congress, August 28, 2023, Amsterdam, Netherlands.

The goal of the trial was to compare the safety and efficacy of clopidogrel monotherapy compared with dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) as maintenance therapy after completion of 9–12 months of DAPT following drug-eluting stent (DES) PCI for ACS.

Study Design: A total of 7700 eligible patients were randomized in a 1:1 double-blinded fashion to either clopidogrel monotherapy (n = 3,850) or continued DAPT with aspirin and clopidogrel (n = 3850) for an additional 9 months following successful completion of 9–12 months of DAPT after initial PCI. Both arms were then switched to aspirin monotherapy for another 3 months. They were followed up for 9 months.

Inclusion Criteria: ACS patients undergoing PCI (new-generation DES) and finishing 9–12 months of DAPT. Patients aged <65 years must meet at least one of each of the clinical criteria of high bleeding risk and high ischemic risk; patients aged 65–75 years must meet one of the following clinical criteria: either high bleeding risk or high ischemic risk.

Clinical Criteria for High Bleeding Risk: Age ≥75 years old, female, iron deficiency anemia, history of stroke (hemorrhagic or ischemic), ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin), and chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 mL/min or creatinine clearance <60 mL/min).

Clinical Criteria for High Ischemic Risk: Age ≥75 years old, multiple coronary lesions, target lesions required for a stent of total length >30 mm, thrombotic target lesions, bifurcation lesions are medina 0, 1, 1 or 1, 1, and 1, with stents implanted in both the main branch and the side branch, left main coronary artery (≥50%) or proximal left anterior descending artery (≥70%) lesions, calcified plaques requiring endovascular excision, ACS with troponin positive. Previous MI, ischemic stroke, diagnosed peripheral arterial disease (PAD), or revascularization due to coronary artery disease/PAD, recurrent MI, revascularization, stent thrombosis, stroke in the last 9 months, ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin), chronic kidney disease (eGFR <60 mL/min or creatinine clearance <60 mL/min).

Exclusion Criteria: Discontinuation or termination of DAPT treatment during the past 6 months due to adverse events (bleeding or ischemia) or other conditions, surgery plan within 90 days, coronary revascularization (surgical or intervention) program within 90 days, dialysis-dependent renal failure, moderate or severe hepatic insufficiency (two times the upper limit of normal for ALT or AST), life expectancy <1 year, unable or unwilling to provide informed consent, women with childbearing potential, platelet count <100,000/mm³, subjects undergoing warfarin or similar anticoagulant therapy.

Results: The primary endpoint, clinically relevant bleeding (Bleeding Academic Research Consortium [BARC] 2, 3, or 5) at 9 months for clopidogrel monotherapy vs. DAPT was: 2.5% vs. 3.3% (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.57-0.97, p = .03). BARC 3, 5 bleeding, was: 0.5% vs. 0.7% (p > .05). Secondary outcomes for clopidogrel monotherapy vs. DAPT: Major adverse cardiovascular events (all-cause death, MI, stroke, and clinically indicated revascularization): 2.6% vs. 3.5% (HR 0.74, 95% CI 0.57−0.96, p = .02), All-cause mortality: 0.3% vs. 0.5% (p > .05), ischemic stroke: 0.7% vs. 0.8% (p > .05), stent thrombosis: 0.05% vs. 0.03% (p> .05)

Comments: The results of the trial showed that in patients at risk of high bleeding and ischemia, after completion of 9–12 months of DAPT (aspirin and clopidogrel) post-DES PCI for an ACS, switching to clopidogrel monotherapy is superior to continued DAPT for an additional 9 months. This resulted in reduced ischemic and bleeding events proving both efficacy and safety. The results are interesting and contrary to what has been observed in the DAPT trial where for more than 12 months the DAPT was superior to aspirin monotherapy. Is it the clopidogrel the game changer or excessive bleeding of aspirin that led to the contrary results? in patients with high bleeding and ischemic risk. The exact duration of treatment with clopidogrel (lifelong?) and its efficacy compared with aspirin for maintenance therapy is unclear, although there is increasing data to suggest that P2Y12 inhibitors may be better than aspirin for secondary prevention from a long-term perspective.

STOP DAPT 3

Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-3

Professor M. Natsuaki STOPDAPT-3: An Aspirin-Free antithrombotic strategy for percutaneous coronary intervention Presented at European Society of Cardiology Congress, August 26, 2023, Amsterdam, Netherlands.

Description: The goal of the trial was to compare the safety and efficacy of an aspirin-free strategy among patients undergoing PCI or at high bleeding risk.

Study Design: Eligible patients were randomized in a 1:1 open-label fashion to either DAPT with aspirin and prasugrel (n = 2,982) or prasugrel monotherapy (n = 2984). Aspirin dose was 81–100 mg/day and prasugrel was 3.75 mg daily. Both groups received a loading dose of 20 mg of prasugrel. A total of 5966 participants were followed up for 1 month. The mean age was 71.6 years and 23% were females.

Inclusion Criteria: Patients who are planning to have PCI with exclusive use of everolimus-eluting stents (Xience series), high bleeding risk defined by the Academic Research Consortium (ARC) or ACS, who could take DAPT with aspirin and P2Y12 inhibitors for 1 month.

Exclusion Criteria: Contraindication to the antiplatelet drugs

Results: 75% had ACS, of which 42.8% had STEMI.

Principal Findings: The primary bleeding endpoint and major bleeding events (BARC 3 or 5) for prasugrel monotherapy versus DAPT were 4.47% and 4.71% (HR 0.95, 95% CI 0.75–1.20; p for superiority = .66). The co-primary cardiovascular endpoint (a composite of cardiovascular death, MI, definite stent thrombosis, or stroke) at 1 month: 4.12% and 3.69% (HR 1.12, 95% CI 0.87–1.45; p for noninferiority = .01).

Secondary Outcomes for Prasugrel Monotherapy vs. DAPT: Any unplanned coronary revascularization: 1.05% vs. 0.57% (HR 1.83, 95% CI 1.01–3.30; p < .05), Subacute definite or probable stent thrombosis: 0.58% vs. 0.17% (HR 3.40, 95% CI 1.26–9.23; p < .05).

Comments: This trial showed that prasugrel (3.75 mg/day) was not superior to DAPT with aspirin 81–100 mg/day and prasugrel 3.75 mg/day in reducing bleeding events in Korean patients undergoing PCI with Xience DES (ACS/high-bleeding risk patients). The cardiovascular events met the non-inferiority criteria; however, they were high in the monotherapy group at 30 days (3.4 times high risk of subacute stent thrombosis, efficacy concern). This trial emphasizes that DAPT should be given post-PCI for at least 1 month (to prevent subacute stent thrombosis) even in high-bleeding risk patients with ACS, thereby saying that immediate de-escalation to the P2Y12 inhibitor is harmful. The DAPT should remain the standard strategy for 1 month after the coronary stent implantation. Instead of 3.75 mg/day, a dose of 5 mg/day prasugrel would have changed the results in this trial (i.e., reducing subacute stent thrombosis) is the question to be addressed.

SHARE

(Short-term Dual Antiplatelet Therapy After Deployment of BioabsoRbable Polymer Everolimus-Eluting Stent) Trial

Professor Pil-Ki Min. SHARE trial: P2Y12 Inhibitor Monotherapy vs DAPT After PCI presented at European Society of Cardiology Congress, August 25, 2023, Amsterdam Netherlands.

The traditional use of DAPT post-PCI is for at least 12 months. How optimally the duration can be shortened without risking the occurrence of ischemic events is a question of debate. Advances in DESs favored the short duration of DAPT to a minimum of 1 month, 3 months, or 6 months in different subsets. This trial aimed to compare the efficacy and safety of P2Y12 monotherapy after 3 months of DAPT vs. 12 months of DAPT who underwent successful PCI with the latest DES.

Methodology: It is a prospective randomized, open-label non-inferiority trial in South Korea (20 hospitals). The enrolment was between 2017 and 2022 with follow-up until the completion of the trial. Clopidogrel was used in CCS, Ticagrelor or Clopidogrel was used in ACS. They were randomized in 1:1 vs. DAPT. After successful PCI and 3 months of DAPT.

Exclusion Criteria: Age ≥86 years; hemodynamically unstable patients; patients at high risk of bleeding, anemia, or thrombocytopenia; patients requiring oral anticoagulation; life expectancy less than 1 year; patients with a history of intracranial hemorrhage; patients unable to take aspirin, clopidogrel, or ticagrelor due to contraindications of each agent; history of coronary stenting within 1 year; LM disease requiring intervention; CTO lesion requiring intervention; ISR lesion requiring intervention; bifurcation lesions requiring stenting in the side branches; lesions requiring overlap of 3 or more stents.

Primary Outcomes: Net adverse clinical event (NACE): a composite of MACCE (cardiac death, MI, stent thrombosis, stroke, or TLR) & major bleeding (BARC type 3 or 5 bleeding) (3–12 months after the index PCI)

Secondary Outcomes: MACCE, major bleeding, cardiac death, MI, stent thrombosis, stroke, TLR, TVR, and all-cause death

Major Findings: The absolute difference of NACE for 3 months, −0.44% (95% CI, −1.19 to 0.32) (P for noninferiority <.001) and the absolute difference of NACE for 12 months, −0.93% (95% CI, −2.64 to 0.77) (P for noninferiority <.001). Major bleeding was 1 (0.2%) in the monotherapy vs. 5 (0.8%) in DAPT (absolute difference −0.6 (−1.33, 0.12) p = .104), Stent thrombosis 1 (0.2%) in the monotherapy vs. 1 (0.2%) in DAPT (absolute difference 0.03 (−0.55, 0.6) p = .929). In subgroup analysis, no differences in all subgroups.

Conclusion: The P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT in terms of NACE.

Comments: When an open-label trial is done, several limitations are expected. The adherence rate to the drug was less. The expected event rate was low (now is this because of nonadherence to the drug or really the efficacy of the drug?). There is a wide non-inferiority margin, and it is done only in South Korea.

With the available evidence from TWILIGHT, TICO, STOPDAPT-2-ACS, MASTER DAPT, etc., the recent 2023 ACS guidelines state that “Considering the totality of evidence from the scientific literature, alternatives to the default strategy of 12 months DAPT in patients with ACS include shortening the DAPT duration to 1 or 3–6 months (depending on the balance of bleeding and ischemic risks) and de-escalating DAPT from prasugrel/ticagrelor-based DAPT to clopidogrel-based DAPT. Most of the trials are powered for the evaluation of bleeding outcomes (safety outcomes, non-inferiority) and were not powered adequately to evaluate ischemic outcomes (efficacy outcome).” Practically, these strategies are not to be employed as a default strategy in the ACS population but can be tried in patients to reduce the risk of bleeding in HBR patients or in cases with concerns about continuing the 12 months of DAPT.

RIGHT

Shaoping Nie. Post-procedural anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a multicentre, randomised, double-blind trial. Presented at European Society of Cardiology Congress, August 28,2023, Amsterdam, Netherlands.

Materials and Methods: This trial was done in 53 centers across China. A total of 2989 patients with STEMI undergoing PCI in these centers were randomized to receive a placebo (1495) or low-dose post-procedural anticoagulation (PPA) consisting of enoxaparin or unfractionated heparin or bivalirudin (n = 1494) for at least 48 h. Each center can follow any one regimen. The primary efficacy objective is to demonstrate the superiority of PPA in reducing all causes of death, non-fatal MI, non-fatal stroke, definite stent thrombosis, or urgent revascularization of any vessel within 30 days.

Results: The mean age of participants was 60.9 years. 20.7% were women. Hypertension was seen in 54.5% and 24.5% had diabetes. The primary efficacy endpoint was noted in 37 patients (2.5%) in both groups. However, when observed for the efficacy of the individual anticoagulant in reducing the events, there was a significant interaction noted (p = .015); enoxaparin vs. placebo, HR 0.46; unfractionated heparin vs. placebo, HR 3.71; and bivalirudin vs. placebo, HR 1.24. There was no excess major bleeding globally or in any of the three individual groups.

Comments: Post-PCI anticoagulation is a common practice. Now, whether giving anticoagulation for 48 hours in the ICU would reduce ischemic events has been studied. The results showed that the anticoagulation did not reduce the ischemic events. Which anticoagulant is to be given when analysed? enoxaparin edged over the other two. Further studies are required on this regimen before concluding the global application of the results.

C. Preventive Cardiology

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

Global Cardiovascular Risk Consortium, Magnussen C, Ojeda FM, et al. Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality. N Engl J Med. 2023;389(14):1273−1285.

Abstract

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.

Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and eight geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.

Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% CI, 52.4–62.1) among women and 52.6% (95% CI, 49.0–56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8–27.5) and 19.1% (95% CI, 14.6–23.6).

Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors.

Comments: This large global trial showed that all-cause deaths are due to five major modifiable risk factors. Global and regional measures are to be initiated to counteract the deaths through early detection beyond the conventional risk systems (non-HDL cholesterol).

D. Inflammatory Cardiac Disease

ARAMIS: Anakinra to Reduce Complications of Acute Myocarditis?

Doctor E. Ammirati. Discussant Review: ARAMIS. Presented at European Society of Cardiology Congress, August 28, 2023, Amsterdam, Netherlands.

This trial was done in France (six centers). The trial population (120 symptomatic patients) with increased cardiac troponin and acute myocarditis were randomized to either a daily dose of anakinra (100 mg) or a placebo. The primary endpoint was the number of days free of myocardial complications within 28 days post-discharge. They received the drug anakinra or placebo within 72 h of hospital admission and were on the treatment until discharge. The patients received standard care of treatment these 28 days.

Results: The median age of participants was 28 years. Almost 90% were men. The rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients. There was no difference in the number of days free of any myocarditis complications between the two arms, with a median of 30 days for anakinra compared with 31 days for placebo. The safety endpoint involving the number of serious adverse events within 28 days post-discharge occurred in seven patients (12.1%) in the anakinra group and six patients (10.2%) in the placebo group, with no significant difference between groups.

Conclusion: The use of anakinra was safe, but it didn’t result in any complications of myocarditis. A larger study is required to explore the benefit of these agents in high-risk patients as well as low to moderate-risk patients.

Comments: A trial on myocarditis, though small, is to be appreciated for initiating and opening the gates for further hypotheses in this subset. Longer follow-up and a larger population would give the answers.

E. Cardiac Arrest/Cardiogenic Shock

ARREST

Patterson T, Perkins GD, Perkins A, et al. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet. 2023;402(10410):1329−1337.

Background: The International Liaison Committee on Resuscitation has called for a randomized trial of delivery to a cardiac arrest center. We aimed to assess whether expedited delivery to a cardiac arrest center compared with the current standard of care following resuscitated cardiac arrest reduces deaths.

Methods: ARREST is a prospective, parallel, multicenter, open-label, randomized superiority trial. Patients (aged ≥18 years) with the return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomization system to expedite delivery to the cardiac catheter laboratory at one of seven cardiac arrest centers or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in the hospital was not possible. The primary outcome was all-cause mortality at 30 days, analyzed in the intention-to-treat (ITT) population, excluding those with unknown mortality status. Safety outcomes were analyzed in the ITT population. The trial was prospectively registered with the International Standard Randomized Controlled Trials Registry, 96585404.

Findings: Between January 15, 2018, and December 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest center and 431 (50%) to standard care. Twenty participants withdrew from the cardiac arrest centre group and 19 from the standard care group due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of the 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90–1.11; P = ·96). Eight (2%) of 414 patients in the cardiac arrest center group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention.

Interpretation: In adult patients without ST elevation, transfer to a cardiac arrest center following resuscitated cardiac arrest in the community did not reduce deaths.

Comments: This is the first randomized trial to assess the benefit of immediate transfer to a cardiac center following the resuscitated OHCA. Contrary to the available literature of the observational studies, this trial did not show any difference in short-term and long-term mortality compared to standard care. Patients at cardiac arrest centers were evaluated in detail. The study results cannot be generalized for the population studied; however, the role of these centers in resuscitating OHCA cannot be ignored by the negativity seen in this trial.

ECLS SHOCK Trial: Extracorporeal Life Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock

Thiele H, Zeymer U, Akin I, et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. N Engl J Med. 2023;389(14):1286−1297.

Background: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock, despite a lack of evidence regarding its effect on mortality.

Methods: In this multicenter trial, patients with acute MI complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy.

Results: A total of 420 patients underwent randomization, and 417 patients were included in the final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% CI, 0.80–1.19; P = .81). The median duration of mechanical ventilation was 7 days (interquartile range, 4–12) in the ECLS group and 5 days (interquartile range, 3–9) in the control group (median difference, 1 day; 95% CI, 0–2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50–3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31–6.25).

Conclusions: In patients with acute MI complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone.

Comments: The goal of the trial was to evaluate the efficacy of ECLS in improving mortality in patients with acute MI and cardiogenic shock. Among patients with acute MI, ECLS failed to improve survival at 30 days. The major reason was safety concerns in the ECLS group (an increased incidence of moderate or severe bleeding and vascular complications). After this trial results, the use of ECLS in this subset will be challenged.

G. Valvular Heart Disease

RIVER Trial Subanalysis

This subanalysis used two models to differentiate patients into high-risk and low-risk bleeding events and embolic events and compared them to the conventional CHADVASC and HASBLED scores.

To conclude, the subanalysis showed that traditional scores were not accurate in estimating the thromboembolic and bleeding risk in patients with a bioprosthetic mitral valve and presenting with AF and flutter. In terms of the etiology, the rheumatic VHD did not present a higher thromboembolic or bleeding risk. Of the drugs, rivaroxaban was comparable to warfarin in terms of thromboembolic and bleeding risk, regardless of VHD etiology and bleeding risk.

Comments: The RIVER trial is currently the only randomized study to assess the use of new oral anticoagulation compared to warfarin in patients with mitral bioprosthesis and AF/flutter. It will be very important in the future, considering the widespread use of both surgical and transcatheter bioprosthesis. We need to explore whether novel oral anticoagulants are safe and efficacious in patients with valvular heart disease and prostheses with or without AF/flutter.

H. Cardio-Oncology

ONCO DVT Trial

Edoxaban for 12 Months vs. 3 Months in Patients with Cancer and DVT

Doctor Y. Yamashita. ONCO DVT Study; Optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer study. Presented at European Society of Cardiology Congress, August 28, 2023, Amsterdam, Netherlands.

Background: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis (DVT) in patients with cancer is clinically relevant, but the evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for the prevention of thrombotic events; however, it could also increase the risk of bleeding.

Methods: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned cancer patients with isolated distal DVT, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary endpoint was a composite of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Hemostasis. A 12-month edoxaban treatment was superior to a 3-month edoxaban treatment concerning the primary endpoint, which was the hypothesis to be tested.

Results: 604 patients were randomized (April 2019–June 2022). Three patients withdrew their consent and finally, 601 patients were analyzed as per their intention to treat the population. There were 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of DVT at baseline. The primary endpoint of a symptomatic recurrent VTE event or VTE-related death occurred in 3 patients in the 12-month group compared to 22 patients in the 3-month group (1.0% vs. 7.2%, OR 0.13). Major bleeding occurred in 9.5% vs. 7.2%, respectively, OR 1.34. The prespecified subgroups did not affect the estimates of the primary endpoint.

Conclusions: In cancer patients with isolated distal DVT, 12 months was superior to 3 months for an edoxaban treatment concerning the composite outcome of a symptomatic recurrent VTE or VTE-related death.

Comments: Cancer-related DVT is of major concern for bleeding during management. However, the thrombotic risk is also high, which must be balanced. This is the only trial to date to show that a longer duration of anticoagulation therapy is beneficial in reducing thrombotic events in patients with isolated distal DVT. The researchers noted that prespecified subgroup analyses according to age, body weight, and renal function did not affect the estimates on the primary endpoint. The trial results might change the guidelines regarding the management of DVT in cancer patients.

I. Pharmacotherapy

LODESTAR Trial

Rosuvastatin versus Atorvastatin Treatment in Patients with Coronary Artery Disease

Professor M. Hong Rosuvastatin versus atorvastatin treatment in LODESTAR trial. Presented at European Society of Cardiology Congress, August 25, 2023, Amsterdam, Netherlands.

It is a randomized parallel open-label trial. 4,400 enrolees with a mean age of 65 years were followed up for 3 years. Twenty-seven percent were females and 33% were having diabetes. The LDL cholesterol level was 84 mg/dL. Fifty-eight percent were on a moderate-intensity statin, 24% were on a high-intensity statin and 2% were on a low-intensity statin. The primary endpoint was no different between both groups (P = .58).

Comments: Among CAD patients, rosuvastatin was not superior to atorvastatin in preventing the major adverse cardiac events within 3 years. This lack of benefit was despite most patients achieving LDL-C level <70 mg/dL at 3 years in the rosuvastatin group. Rosuvastatin was associated with an excess incidence of initiation of diabetic medications and cataract operations. Based on this study, high-intensity atorvastatin therapy may be preferential to rosuvastatin.

SGLT2i in COVID-19

Professor B. Rocca. Prospective Meta-analysis of SGLT2 inhibitor randomized trials in COVID-19 Presented at European Society of Cardiology Congress, August 28, 2023, Amsterdam, Netherlands.

SGLT inhibitors (hypothesized that they would be beneficial in COVID-19 patients with their pleiotropic effect) did not have any mortality benefit in hospitalized patients due to COVID-19. The DATE, ACTIV 4 RECOVERY TRIALS were analysed. There were no issues regarding safety in this subset on use of SGLT2 inhibitors.

NITRATE CIN

Does Inorganic Nitrate Improve Safety of Coronary Angiography for Patients at Renal Injury Risk?

Doctor D.Jones. NITRATE-CIN: Inorganic nitrate to prevent CIN after angiography for ACS. Presented at European Society of Cardiology Congress, August 28, 2023, Amsterdam, Netherlands.

Researchers randomized a total of 640 patients over 3 years to receive 12 mmol of inorganic potassium nitrate (n = 319) or placebo capsules (n = 321) daily for 5 days.

The mean age of trial participants was 71 years; approximately 73% were men, 75% were Caucasian, 46% had diabetes, and 56% had chronic kidney disease. The median follow-up was 1 year.

The results showed that treatment with inorganic nitrate treatment significantly reduced the occurrence of CIN when compared to placebo (9.1% vs. 30.5%, respectively). This difference persisted after adjustment for the presence of diabetes and baseline creatinine levels. The rate of procedural MI, improved renal function, and reduction of MACE at 1 year (secondary outcomes) also favored the use of inorganic nitrate.

Comments: To date, many trials conducted for the prevention of CIN have been negative except for the efficacy of hydration with normal saline and probably the role of statins. This trial is the first to show that a drug is effective in preventing CIN by 20%.