Highlights of Acute Coronary Syndromes

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New evidence for acute coronary syndrome has been presented in Hot Line sessions at the 2022 European Society of Cardiology Congress in Barcelona. This editorial describes some of the highlights.

Disclosure:ARM is on the editorial board of European Cardiology Review; this did not influence peer review. ARM reports honoraria from Astra-Zeneca, Boehringer, Bayer, Janssen, MSD, Novartis and Viphor.



Published online:

Correspondence Details:Alejandro Recio-Mayoral, Department of Cardiology, Hospital Universitario Virgen Macarena, Avda. Doctor Fedriani nº3, 41009, Seville, Spain. E: alejandro.recio.sspa@juntadeandalucia.es

Open Access:

This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.


This multicenter open-label trial conducted at 14 sites in Korea included 563 patients with acute MI (AMI) and multivessel disease who had successful revascularisation of the infarct-related artery (IRA). Patients were randomised to undergo non-IRA revascularisation with either fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with FFR ≤0.80 (the FFR group; n=284) or visual estimation angiography-guided PCI with >50% diameter stenosis (the angiography group; n=278).

After a median follow up of 3.5 years, the composite endpoint – a composite of all-cause death, MI or unplanned revascularisation – strongly favoured patients randomised to the FFR group, at 7.4% versus 19.7% in patients in the angiography group (HR 0.43; 95% CI [0.25–0.75]). Significant advantages were observed across the individual outcomes of both death and MI in the FFR group. There were also numerical trends towards benefit in unplanned revascularisation.

Although the trial was terminated early because of the COVID-19 pandemic – far short of the planned 1,292 patients – the findings shed light on the efficacy and safety of performing a selective PCI of non-IRA lesions using FFR-guided decision making in patients with AMI and multivessel disease. In clinical practice, the adoption of this strategy may reduce the risk of death, MI or repeat revascularisation with fewer numbers of stents and less contrast media use than angiography-guided PCI.

PACIFIC-AMI: Efficacy and Safety of the Factor XIa Inhibitor Asundexian on Top of Dual Antiplatelet Therapy after AMI

Asundexian, a novel oral inhibitor of activated coagulation factor XIa, might reduce thrombosis with minimal effect on haemostasis, according to this research.

The multicenter, Phase II PACIFIC-AMI trial explored the pharmacodynamics, safety and efficacy of three doses of asundexian, (10, 20 and 50 mg, taken once a day) on top of dual antiplatelet therapy (aspirin and a P2Y12 inhibitor) in 1,601 patients, aged ≥45 years, enrolled within 5 days after the index AMI event.1 Almost all patients (99%) underwent PCI before randomisation and 80% were treated with aspirin and prasugrel or ticagrelor. The primary efficacy outcome was the composite of cardiovascular death, MI, stroke and stent thrombosis and the primary safety endpoint was Bleeding Academic Research Consortium bleeding definition types 2, 3 and 5.

After a median follow-up of 368 days, asundexian produced dose-related inhibition of factor XIa, reaching >90% with the 50 mg dose, but potentially without an increase in bleeding at any dose or compared with placebo. There was also no significant reduction in ischaemic events with asundexian, although the trial was not powered to test for differences in thrombotic events.

These findings warrant adequately-sized Phase III clinical trials to further evaluate asundexian as a potentially safer anticoagulant for patients following an AMI.

PARADISE-MI Trial: Win Ratio Analysis

In the PARADISE-MI trial, more than 5,600 patients with AMI and left ventricular ejection fraction ≤40% and/or pulmonary congestion plus any risk enhancer were randomised to sacubitril/valsartan or ramipril.2 For the primary endpoint (time to first event of cardiovascular death, heart failure [HF] hospitalisation or outpatient development of HF), all of them adjudicated by a clinical event classification (CEC) committee, sacubitril/valsartan had a numerical advantage but did not reach statistical significance.

Data from PARADISE-MI were re-evaluated in this post-hoc win ratio analysis, by considering the hierarchy of the endpoints (more serious events are given higher priority and are analysed first) and by increasing the totality of evidence with events confirmed by the CEC committee and investigator-reported events that may not have met original study definitions.3 The hierarchical analysis of the primary composite outcome showed a larger number of wins for sacubitril/valsartan for a total win ratio of 1.17 (95% CI [1.03–1.33]; p=0.015). The contribution to the number of wins was greatest for cardiovascular death (36.9%) and HF hospitalisation (29.8%). CEC-committee-confirmed events accounted for approximately 70% of the wins, while the remaining 30% of the wins came from events that were not adjudicated.

These results do not replace the initial neutral trial results, but instead can be used to aid decision making to replace angiotensin-converting-enzyme inhibitors with sacubitril/valsartan once symptomatic HF has developed. Future clinical trials should consider the hierarchy of the events and, perhaps, some of the CEC committee definitions should be reviewed to find those closer to clinical practice.

The Radial Trialists’ Collaboration Meta-analysis: Radial Versus Femoral Access for Coronary Procedures

Based on findings from a large meta-analysis of individual patient data from seven randomised clinical trials, comprising a total of 21,600 patients, of which 10,775 were randomised to transradial access (TRA) and 10,825 were randomised to transfemoral access. The median age of participants was 63.9 years, 95% presented with acute coronary syndrome and 75.2% underwent PCI. TRA significantly reduced the risk of all-cause mortality and major bleeding at 30 days compared with trans-femoral access. Notably, the benefit of TRA was substantial in patients with significant anaemia, while it was not in those with milder or no baseline anaemia. Importantly, the benefit of TRA on mortality was only partially driven by major bleeding prevention. Elucidating the ancillary mechanisms will be required to fully explain the causal association.


  1. Rao SV, Kirsch B, Bhatt DL, et al. A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor XIa inhibitor asundexian to prevent adverse cardiovascular outcomes following acute myocardial infarction. Circulation 2022; epub ahead of press.
    Crossref | PubMed
  2. Pfeffer MA, Claggett B, Lewis EF, et al. Angiotensin receptor–neprilysin inhibition in acute myocardial infarction. N Engl J Med 2021;385:1845–55.
    Crossref | PubMed
  3. Berwanger O, Pfeffer M, Claggett B, et al. Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win-ratio analysis of the PARADISE-MI trial. Eur J Heart Fail 2022; epub ahead of press.
    Crossref | PubMed