Vol 8, No 1 (2023)
Invited editorial
Published online: 2023-02-06

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Antiplatelet treatment for older patients with ACS — a challenging issue

Stefano De Servi12, Antonio Landi12
Medical Research Journal 2023;8(1):1-4.


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Medical Research Journal 2023;
Volume 8, Number 1, 1–4, 10.5603/MRJ.a2023.0002,
Copyright © 2023 Via Medica,
ISSN 2451-2591

e-ISSN 2451-4101

Antiplatelet treatment for older patients with ACS a challenging issue

Stefano De Servi12Antonio Landi12
1Department of Molecular Medicine, University of Pavia Medical School, Pavia, Italy
2Division of Cardiology, Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland

Corresponding author:

Stefano De Servi, MD, FESC, Professor of Cardiology, Department of Molecular Medicine, University of Pavia Medical School, 27100, Pavia, Italy; e-mail: stefano.deservi01@gmail.com

Patients with75 years of age represent a large and significant proportion of those admitted for acute coronary syndromes (ACS) in our hospitals [1]. Older patients frequently present with peculiar features and comorbidities (complex coronary lesions, anaemia, chronic kidney dysfunction, peripheral vascular disease) associated with geriatric syndromes (frailty, disability, cognitive impairment) that are relevant determinants of patients health and outcomes [2]. Older adults have frequently low-grade inflammation (“inflammaging”) which has been associated with the occurrence of frailty and with the development of the atherosclerotic process [2]. The prevalence of frailty increases as age advances and is more frequent among elderly women: it is present in more than 20% of patients with 80 to 84 years of age [2, 3]. Cognitive impairment is not infrequent among frail older patients and may deteriorate at the time of ACS presentation, due to the stress of the acute event, the unfamiliar environment and side effects of medications [2]. Because older patients are underrepresented in clinical trials, evidence for more precise treatments is still limited and the cardiologist has to rely on his own clinical judgement to select the most appropriate treatment strategies [1, 2]. It is important to emphasize that therapeutic management of older patients should be more individualized than in younger ones, because the clinicians have to take into consideration comorbid medical and geriatric conditions that are not included in traditional ACS risk scores (Fig. 1). Patients presenting with persistent ST-segment elevation myocardial infarction (STEMI) are currently treated with mechanical reperfusion by percutaneous coronary intervention (PCI). The European Society of Cardiology (ESC) STEMI guidelines recommend “no upper age limit with respect to reperfusion, especially with primary PCI” [4], despite relatively few data concerning outcomes of older patients undergoing primary PCI. Although more information is available from randomized trials specifically focused on elderly patients with non-ST-segment elevation ACS (NSTE-ACS) than in STEMI in favour of an invasive approach [5, 6], the different presentation at admittance (patients with STEMI have ongoing ischemia while NSTE-ACS may be asymptomatic) may favour the clinical choice of an initially conservative strategy. Coronary angiography and PCI are seldom performed in frail patients who are thought to be at higher risk if treated invasively. In this regard, observational registries provided conflicting data: no benefit was observed in the Spanish LONGEVO registry, whereas a better outcome was associated with PCI in the ISACS-TC registry [1].

Antiplatelet therapy in older patients with ACS

Since older patients are more liable to bleeding complications than younger ones due to the presence of clinical comorbidities that increase bleeding risk [1, 2], the choice of an appropriate antiplatelet strategy is difficult to pursue. Moreover, the large pivotal trials on dual antiplatelet therapy (DAPT) comparing potent P2Y12 inhibitors with clopidogrel (TRITON-TIMI 38 and PLATO) enrolled few aged patients [7, 8]. Because prasugrel at 10 mg significantly increased bleeding, its use in older patients was not recommended by Food and Drug Administration (FDA) whereas a 5 mg/day maintenance dose was indicated by the European Medicines Agency [9]. In PLATO the superiority of a DAPT regimen with ticagrelor over a DAPT with clopidogrel (including a reduction in cardiovascular mortality) was confirmed in older patients enrolled in that trial [10].

Figure 1. Key factors contributing to the geriatric syndrome including cognitive decline, disability, delirium, frailty, polypharmacy and multimorbidity

Yet, recent trials specifically undertaken in elderly patients did not support the findings of that PLATO sub-analysis. The POPular AGE study showed that a DAPT including clopidogrel significantly decreased bleeding rates (including fatal bleeding) compared with a DAPT with ticagrelor, without any increase in thrombotic complications [11]. Patients taking clopidogrel and prasugrel 5 mg maintenance dose had similar rates of bleeding and thrombotic events in the randomized ELDERLY ACS 2 trial [12]. In the 5 mg prasugrel arm, thrombotic events were lower during the first month of treatment, whereas bleeding events were higher than in the clopidogrel arm in the late phase of the trial (31365 days) [13]. Despite the large response variability observed after clopidogrel administration and subsequent high on-treatment platelet reactivity in a not negligible proportion of patients [14], the refined technology of new drug-eluting stents and improved operator expertise may have made unnecessary the requirement of potent antiplatelet agents [15].

DAPT composition and duration should be tailored on individual patients according to the thrombotic and bleeding risk. Current guidelines recommend the use of scores, especially for the assessment of bleeding [16]. For that purpose, the PRECISE DAPT score and the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria are helpful tools for the clinician [16] to estimate the bleeding risk and establish tailored treatments. Advanced age is a well-known risk factor for bleeding events. However, the large majority of older patients with ACS carry both high bleeding and thrombotic risk: in the ELDERLY-ACS 2 trial more than two thirds of patients (68%) satisfied the criteria for the definition of high thrombotic risk according to the ARC-HBR trade-off model [17] that reported the predictors of thrombotic complications in patients undergoing stent implantation who met the ARC-HBR definition.

Based on available evidence, we believe that a short DAPT should be the preferred strategy in elderly patients with isolated HBR. One-month DAPT, followed by antiplatelet monotherapy, was non-inferior to standard DAPT for net and major adverse clinical events and significantly reduced bleeding in the MASTER DAPT trial [18] that randomized only HBR patients undergoing PCI (with more than two thirds aged75 years). However, one-month DAPT seems a too short DAPT treatment in ACS, since these patients may incur in an excess of cardiovascular events (particularly MI) as shown by the One-month DAPT trial [19]. Clopidogrel seems preferable to ticagrelor [11] for the initial DAPT period for a better safety profile and comparable efficacy; clopidogrel may also be preferred to aspirin as long-term monotherapy, due to a lower discontinuation rate for gastrointestinal discomfort or bleeding, frequently associated with aspirin use in older patients.

A de-escalation strategy appears suitable for patients in whom HBR is associated with a high thrombotic risk [20]. In a post-hoc analysis of the Elderly ACS-2 trial, low-dose prasugrel reduced thrombotic complications in the subacute (first month after index event) and chronic phases (from second month to 1 year) compared with clopidogrel, whereas bleeding was lower with clopidogrel in the late phase [13]. In these patients, an initial DAPT including low-dose prasugrel followed after 23 months by a DAPT with clopidogrel up to 12 months appears an appropriate strategy. However, these considerations are speculative and need to be confirmed by randomized trials conducted in elderly ACS populations.

In conclusion, although the appropriate use of antiplatelet agents in older ACS patients is challenging, the evidence is in favour of a cautious approach, avoiding potent P2Y12 inhibitors like full-dose prasugrel and ticagrelor and relying on clopidogrel for initial DAPT and subsequent monotherapy. Short DAPT or de-escalation appear also suitable strategies, whose choice should be based on the assessment of the bleeding and the thrombotic risk.


  1. Morici N, De Servi S, De Luca L, et al. Management of acute coronary syndromes in older adults. European Heart Journal. 2021; 43(16): 15421553, doi: 10.1093/eurheartj/ehab391.
  2. Damluji AA, Forman DE, Wang TY, et al. American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; and Council on Lifestyle and Cardiometabolic Health. Management of Acute Coronary Syndrome in the Older Adult Population: A Scientific Statement From the American Heart Association. Circulation. 2023; 147(3): e32e62, doi: 10.1161/CIR.0000000000001112, indexed in Pubmed: 36503287.
  3. Damluji AA, Chung SE, Xue QL, et al. Physical Frailty Phenotype and the Development of Geriatric Syndromes in Older Adults with Coronary Heart Disease. Am J Med. 2021; 134(5): 662671.e1, doi: 10.1016/j.amjmed.2020.09.057, indexed in Pubmed: 33242482.
  4. Ibanez B, James S, Agewall S, et al. [2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.]. Kardiol Pol. 2018; 76(2): 229313, doi: 10.5603/KP.2018.0041, indexed in Pubmed: 29457615.
  5. Savonitto S, Cavallini C, Petronio AS, et al. Italian Elderly ACS Trial Investigators. Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial. JACC Cardiovasc Interv. 2012; 5(9): 906916, doi: 10.1016/j.jcin.2012.06.008, indexed in Pubmed: 22995877.
  6. Tegn N, Eek C, Abdelnoor M, et al. After Eighty study investigators, After Eighty study investigators. Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial. Lancet. 2016; 387(10023): 10571065, doi: 10.1016/S0140-6736(15)01166-6, indexed in Pubmed: 26794722.
  7. Wiviott S, Braunwald E, McCabe C, et al. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. New England Journal of Medicine. 2007; 357(20): 20012015, doi: 10.1056/nejmoa0706482.
  8. Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11): 10451057, doi: 10.1056/NEJMoa0904327, indexed in Pubmed: 19717846.
  9. De Servi S, Goedicke J, Schirmer A, et al. Clinical outcomes for prasugrel versus clopidogrel in patients with unstable angina or non-ST-elevation myocardial infarction: an analysis from the TRITON-TIMI 38 trial. Eur Heart J Acute Cardiovasc Care. 2014; 3(4): 363372, doi: 10.1177/2048872614534078, indexed in Pubmed: 24818952.
  10. Husted S, James S, Becker RC, et al. PLATO study group. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012; 5(5): 680688, doi: 10.1161/CIRCOUTCOMES.111.964395, indexed in Pubmed: 22991347.
  11. Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020; 395(10233): 13741381, doi: 10.1016/S0140-6736(20)30325-1, indexed in Pubmed: 32334703.
  12. Savonitto S, Ferri L, Piatti L, et al. Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. Circulation. 2018; 137(23): 24352445, doi: 10.1161/circulationaha.117.032180.
  13. Crimi G, Morici N, Ferrario M, et al. Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel. J Am Heart Assoc. 2019; 8(2): e010956, doi: 10.1161/JAHA.118.010956, indexed in Pubmed: 30636561.
  14. De Servi S, Crimi G, Calabrò P, et al. Relationship between diabetes, platelet reactivity, and the SYNTAX score to one-year clinical outcome in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. EuroIntervention. 2016; 12(3): 312318, doi: 10.4244/EIJV12I3A51, indexed in Pubmed: 27320425.
  15. De Servi S, Landi A, Savonitto S. Antiplatelet Therapy in Elderly Patients with Acute Coronary Syndromes: the Clopidogrel Revenge: Possible Reasons for a Bright Comeback. Cardiovasc Drugs Ther. 2021; 35(2): 399401, doi: 10.1007/s10557-020-07055-0, indexed in Pubmed: 32809109.
  16. Collet JP, Thiele H, Barbato E, et al. Siontis GCM; ESC Scientific Document Group 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021; 42: 12891367.
  17. Urban P, Gregson J, Owen R, et al. Assessing the Risks of Bleeding vs Thrombotic Events in Patients at High Bleeding Risk After Coronary Stent Implantation: The ARC-High Bleeding Risk Trade-off Model. JAMA Cardiol. 2021; 6(4): 410419, doi: 10.1001/jamacardio.2020.6814, indexed in Pubmed: 33404627.
  18. Valgimigli M, Smits PC, Frigoli E, et al. MASTER DAPT Investigators, MASTER DAPT Investigators. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021; 385(18): 16431655, doi: 10.1056/NEJMoa2108749, indexed in Pubmed: 34449185.
  19. Hong SJ, Kim JS, Hong SJ, et al. One-Month DAPT Investigators. 1-Month Dual-Antiplatelet Therapy Followed by Aspirin Monotherapy After Polymer-Free Drug-Coated Stent Implantation: One-Month DAPT Trial. JACC Cardiovasc Interv. 2021; 14(16): 18011811, doi: 10.1016/j.jcin.2021.06.003, indexed in Pubmed: 34332946.
  20. De Servi S, Landi A, Savonitto S, et al. Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice. J Cardiovasc Med (Hagerstown). 2023; 24(2): 7786, doi: 10.2459/JCM.0000000000001399, indexed in Pubmed: 36583976.