Coronary artery disease (CAD) and acute coronary syndromes (ACS) remain the leading causes of mortality in Western countries (1). In the last decades, technological advancements and optimization of pharmacological and interventional strategies led to a substantial reduction of ACS-associated morbidity and mortality (2). However, a not negligible proportion of post-ACS patients are still exposed to higher risks of fatal and non-fatal adverse events, including re-admission due to myocardial infarction (MI) or heart failure (HF), unplanned revascularization, stroke and bleeding.
Percutaneous coronary intervention (PCI) represents the revascularization modality of choice in ACS patients (3). The wide adoption of radial access (4, 5), newer-generation drug-eluting stents, intravascular imaging-guidance (6), optimized periprocedural antithrombotic treatments (7–9) and novel mechanical thrombectomy devices (10, 11) paved the way to the interventional treatment even in “complex, high-risk and indicated patients” (CHIP). In spite of these advancements, uncertainties exist both in the management of specific high-risk subjects, such as patients following out-of-hospital cardiac arrest (OHCA) or those with diabetes, and on the optimal medical therapy following ACS. The papers published in this research topic shed interesting insights on these crucial aspects.
The safety and effectiveness of immediate vs. delayed invasive coronary angiography (CAG) in patients without persistent ST-segment elevation after OHCA have been investigated in three recent randomized clinical trials (RCTs). In the TOMAHAWK trial, including 554 post-OHCA patients without ST-segment elevation, there were no significant differences in the primary endpoint of all-cause death at 30 days between the two strategies [hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.00–1.63; P = 0.06] (12). The COACT (13) and EMERGE (14) trials yelded similar results at 90 and 180 days, respectively. Ahmed et al. summarize all available evidence on this by performing a systematic review and meta-analysis of observational studies (n = 9) and RCT (n = 7) encompassing a total of 4,737 OHCA patients without ST-segment elevation. The authors found that, compared with delayed or no CAG, early CAG was associated with lower long-term mortality [odd ratio (OR), 0.66; 95% CI, 0.51–0.85] and increased favorable cerebral performance at discharge (OR, 1.49; 95% CI, 1.09–2.03). However, this benefit mainly accrued from observational studies, while no benefit of immediate CAG was found when RCTs were separately appraised. Therefore, these results should be interpreted with caution due to different timeframes for early/delayed CAG (ranging from <2 to 6 h for early and from 6 h to 30 days for delayed CAG) and potential unmeasured confounders in observational studies.
Diabetes mellitus (DM) is associated with an impaired prognosis following ACS (15). In a large retrospective analysis from the FAST-MI program (n = 9,181 MI patients of whom 22% had DM), Bouisset et al. investigated the prognostic impact of DM on long-term survival. After propensity score matching, DM was associated per se with a 30% higher risk of mortality (HR, 1.30; 95% CI, 1.17–1.45; p < 0.001). As correctly pointed out by the authors, DM-associated microvascular damage and coronary microvascular dysfunction (not captured in the study dataset) could potentially explain this mortality excess.
Patients with ACS undergoing PCI require a treatment combination of different pharmacological agents to reduce the risk of adverse events. The pharmacological cornerstones include antithrombotic agents, lipid-lowering treatments, anti-RAAS (renin–angiotensin–aldosterone system), β-blockers and metabolic-acting agents (if clinically indicated). Current European Society of Cardiology (ESC) guidelines provide a framework for a tailored implementation of different treatment options (3). Among ACS patients without indication for oral anticoagulation, dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor is recommended for 12 months unless there is high bleeding risk (3, 16). DAPT de-escalation strategies have repeteadly shown to reduce bleeding without ischemic harm (17–21) and are recommended with class IIa–IIb by the 2023 ESC guidelines on ACS (3). Current guidelines recommend to achieve an LDL-colesterol level of <1.4 mmol/L (<55 mg/dl) and to reduce LDL-colesterol by ≥50% from baseline (class of recommendation I, level of evidence A) (3). β -blockers are recommended in patients with left ventricular dysfunction [ejection fraction (EF) ≤40%], while RAAS inhibitors are recommended in ACS patients with HF symptoms, LVEF ≤40%, DM, hypertension, and/or chronic kidney disease (both with class of recommendation I, level of evidence A).
The current research topic provides evidence on the value of β-blockers and sodium–glucose cotransporter (SGLT)-2 inhibitors in ACS. In a retrospective analysis from the CCC-ACS project (n = 113,650 ACS patients), Zhang et al. investigated the prognostic impact of β-blockers in ACS patients with concomitant chronic obstructive pulmonary disease (COPD). Of the 1,084 patients with ACS and COPD, 540 patients received an early β-blocker therapy (within 24 h after hospital admission), whereas 544 did not. After adjustment, the authors found that early β-blocker treatment was associated with a 77% relative reduction in the risk of all-cause death (OR, 0.33; 95% CI, 0.12–0.92; P = 0.035) and a 37% relative reduction in the risk of HF (OR, 0.63; 95% CI, 0.41–0.94; P = 0.025). These data confirm the efficacy of β-blocker therapy in this subpopulation and dispel concerns on the potential effect of β -blocker induced bronchospasm in COPD patients. In another retrospective study including 465 diabetic patients with ACS complicated by acute HF, Rahhal et al. investigated the impact of SGLT-2 inhibitors on short and long-term clinical outcomes. The primary study endpoint was the composite of ACS, HF hospitalization or all-cause mortality at 1 and 12 months after discharge. SGLT-2 treatment was associated with lower risks of the primary composite endpoint at 1 (HR, 0.20; 95% CI, 0.04–0.94; P = 0.041) and 12 months (HR, 0.46; 95% CI, 0.22–0.99; P = 0.046), mainly due to lower risks of HF hospitalization. These studies lend support to the use of early β-blocker treatment in ACS patients with COPD and SGLT-2 inhibitors in diabetic patients with ACS complicated by acute HF. Further larger, randomized studies are needed to confirm these findings.
In conclusion, despite notable improvements, a not negligible proportion of ACS patients remains at higher risk of adverse events. Importantly, studies in this research topic outline potential strategies to mitigate this “residual risk” in ACS patients.
Statements
Author contributions
AL: Conceptualization, Validation, Writing – original draft, Writing – review & editing. AV: Writing – review & editing. VV: Writing – review & editing. AM: Supervision, Validation, Writing – review & editing.
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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
1.
Timmis A Kazakiewicz D Townsend N Huculeci R Aboyans V Vardas P . Global epidemiology of acute coronary syndromes. Nat Rev Cardiol. (2023) 20(11):778–88. 10.1038/s41569-023-00884-0
2.
Valgimigli M Landi A . Ischemic and bleeding risk in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention: is it time to REACT?Eur Heart J Acute Cardiovasc Care. (2021) 10(10):1125–8. 10.1093/ehjacc/zuab090
3.
Byrne RA Rossello X Coughlan JJ Barbato E Berry C Chieffo A et al 2023 ESC guidelines for the management of acute coronary syndromes: developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. (2023) 44(38):3720–826. 10.1093/eurheartj/ehad191
4.
Landi A Branca M Vranckx P Leonardi S Frigoli E Heg D et al Radial versus femoral access in ACS patients undergoing complex PCI is associated with consistent bleeding benefit and no excess of risks. Can J Cardiol. (2022) 38(10):1488–500. 10.1016/j.cjca.2022.06.014
5.
Valgimigli M Landi A . Large-bore radial access for complex PCI. JACC Cardiovasc Interv. (2021) 14(12):1304–7. 10.1016/j.jcin.2021.04.013
6.
Milzi A Landi A Dettori R Burgmaier K Reith S Burgmaier M . Multimodal intravascular imaging of the vulnerable coronary plaque. Echocardiography. (2024) 41(12):e70035. 10.1111/echo.70035
7.
Landi A Valgimigli M . Antithrombotic therapy in patients with established atherosclerotic coronary disease. Heart. (2023) 109(13):1034–43. 10.1136/heartjnl-2022-321603
8.
De Servi S Landi A Savonitto S De Luca L De Luca G Morici N et al Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice. J Cardiovasc Med. (2023) 24(2):77–86. 10.2459/JCM.0000000000001399
9.
De Servi S Landi A Savonitto S Morici N De Luca L Montalto C et al Antiplatelet strategies for older patients with acute coronary syndromes: finding directions in a low-evidence field. J Clin Med. (2023) 12(5):2082. 10.3390/jcm12052082
10.
Landi A Pedrazzini G Wild L Beele A Nafi M Joner M et al Coronary embolisation of native aortic valve debris during transcatheter aortic valve replacement: mechanical embolectomy and histopathological analysis. Lancet. (2024) 403(10422):e5–6. 10.1016/S0140-6736(23)02623-5
11.
Bongiovanni D Loizzi F Landi A Utsch L Araco M Joner M et al Envast mechanical thrombectomy after thrombus aspiration failure in a STEMI with a massive thrombotic burden. JACC Cardiovasc Interv. (2023) 16(1):112–5. 10.1016/j.jcin.2022.09.050
12.
Desch S Freund A Akin I Behnes M Preusch MR Zelniker TA et al Angiography after out-of-hospital cardiac arrest without ST-segment elevation. N Engl J Med. (2021) 385(27):2544–53. 10.1056/NEJMoa2101909
13.
Lemkes JS Janssens GN van der Hoeven NW Jewbali LSD Dubois EA Meuwissen M et al Coronary angiography after cardiac arrest without ST-segment elevation. N Engl J Med. (2019) 380(15):1397–407. 10.1056/NEJMoa1816897
14.
Hauw-Berlemont C Lamhaut L Diehl JL Andreotti C Varenne O Leroux P et al Emergency vs. delayed coronary angiogram in survivors of out-of-hospital cardiac arrest: results of the randomized, multicentric EMERGE trial. JAMA Cardiol. (2022) 7(7):700–7. 10.1001/jamacardio.2022.1416
15.
Roffi M Landi A Heg D Frigoli E Chalkou K Chevalier B et al Abbreviated or standard antiplatelet therapy after PCI in diabetic patients at high bleeding risk. JACC Cardiovasc Interv. (2024) 17(22):2664–77. 10.1016/j.jcin.2024.08.030
16.
Landi A Aboyans V Angiolillo DJ Atar D Capodanno D Fox KAA et al Antithrombotic therapy in patients with acute coronary syndrome: similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines. Eur Heart J Acute Cardiovasc Care. (2024) 13(1):173–80. 10.1093/ehjacc/zuad158
17.
Landi A Caglioni S Valgimigli M . De-escalation in intensity or duration of dual antiplatelet therapy in patients with coronary artery disease: more than alternative treatment options. Eur J Intern Med. (2023) 110:16–8. 10.1016/j.ejim.2023.02.006
18.
Navarese EP Landi A Oliva A Piccolo R Aboyans V Angiolillo D et al Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease: two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute Cardiovascular Care (ACVC), and European Association of Preventive Cardiology (EAPC). Eur Heart J Cardiovasc Pharmacother. (2023) 9(3):271–90. 10.1093/ehjcvp/pvad016
19.
Valgimigli M Aboyans V Angiolillo D Atar D Capodanno D Halvorsen S et al Antithrombotic treatment strategies in patients with established coronary atherosclerotic disease. Eur Heart J Cardiovasc Pharmacother. (2023) 9(5):462–96. 10.1093/ehjcvp/pvad032
20.
Landi A Heg D Frigoli E Vranckx P Windecker S Siegrist P et al Abbreviated or standard antiplatelet therapy in HBR patients. JACC Cardiovasc Interv. (2023) 16(7):798–812. 10.1016/j.jcin.2023.01.366
21.
Valgimigli M Landi A Angiolillo DJ Baber U Bhatt DL Bonaca MP et al Demystifying the contemporary role of 12-month dual antiplatelet therapy after acute coronary syndrome. Circulation. (2024) 150(4):317–35. 10.1161/CIRCULATIONAHA.124.069012
Summary
Keywords
acute coronary syndrome, coronary artery disease, secondary prevention, percutaneous coronary intervention, medical therapy
Citation
Landi A, Varga A, Veulemans V and Milzi A (2025) Editorial: Short and long-term treatment options in patients with acute coronary syndrome. Front. Cardiovasc. Med. 12:1563882. doi: 10.3389/fcvm.2025.1563882
Received
20 January 2025
Accepted
23 January 2025
Published
04 February 2025
Volume
12 - 2025
Edited and reviewed by
Tommaso Gori, Johannes Gutenberg University Mainz, Germany
Updates
Copyright
© 2025 Landi, Varga, Veulemans and Milzi.
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* Correspondence: Antonio Landi antonio.landi@eoc.ch
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.