Acute coronary Syndrome

As the medical community continually strives to optimize patient care, particularly in the realm of cardiovascular health, scrutinizing the efficacy and safety of medications is paramount. A recent letter published in the Revista Española de Cardiología (English Edition) by Dr. Manuel Almendro-Delia and colleagues from the Hospital Universitario Virgen Macarena in Seville, Spain, has brought to light the critical issue of medication discontinuation, notably comparing the risks associated with stopping ticagrelor versus clopidogrel. The correspondence, identified by the record number 38220054, was published on January 12, 2024, with a DOI: 10.1016/j.rec.2023.11.015, adding valuable insights to this ongoing clinical discourse.

There’s a continuous need for comparative studies to understand the repercussions of antiplatelet therapy, particularly when considering altering or discontinuing these medications that are critical in the management of acute coronary syndromes (ACS) and following percutaneous coronary intervention (PCI). Ticagrelor and clopidogrel, both belonging to the class of antiplatelet agents, are central in preventing thrombotic events post-ACS. However, there are distinct differences in their pharmacological profiles which may influence their respective risks upon discontinuation.

The therapeutic conundrum of antiplatelet discontinuation is a complex clinical decision faced by healthcare providers. Dr. Almendro-Delia and his team address this issue by presenting observations and comments on previous studies that shed light on the potential risks associated with cessation of ticagrelor compared to clopidogrel.

The use of ticagrelor, which is a reversibly binding oral P2Y12 receptor inhibitor, has been increasingly favored in clinical settings due to its rapid onset and the predictability of its antiplatelet effects. Clopidogrel, while being another widely used antiplatelet agent, acts as a prodrug requiring hepatic metabolism and has a slower onset of action with more variable platelet inhibition. In clinical practice, understanding the safety profile during and after cessation of these antiplatelet therapies can significantly inform treatment strategies.

In their response letter, Almendro-Delia et al. discuss the data from recent randomized controlled trials and observational studies that examine the occurrence of adverse events following discontinuation of ticagrelor or clopidogrel. They highlight that both early and late discontinuation of these agents can lead to different risks of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death.

Dr. Almendro-Delia’s team emphasizes the challenge in establishing a universal guideline for the discontinuation of antiplatelet therapy due to patient-specific factors, such as bleeding risks, comorbidities, and the necessity of surgery or other medical procedures. Moreover, the intricacies surrounding patient non-compliance and self-discontinuation without proper medical consultation are also underlined as areas of concern.

While the letter does not introduce new primary research data, it serves as an interpretive analysis of existing studies, suggesting that the risk profile for ticagrelor discontinuation may differ from that of clopidogrel. The authors point out that abrupt cessation of ticagrelor, in particular, might result in a transiently increased risk of thrombotic events due to its reversible binding mechanism, as opposed to the irreversible platelet inhibition caused by clopidogrel.

Given these distinctions, the authors call for careful consideration when planning to stop antiplatelet therapy with ticagrelor, advising a transition strategy to another antiplatelet agent if clinically justified. They, however, underscore the need for further research to solidify the evidence base, especially in relation to the phenomenon of ‘rebound’ thrombosis – a hypothetical increased risk of thrombotic events following sudden cessation of antiplatelet drugs.

Dr. Juan C. García-Rubira and Dr. Rafael Hidalgo-Urbano, also from Hospital Universitario Virgen Macarena, contribute to the discussion, underscoring the necessity of careful patient education to prevent unintentional non-adherence to prescribed antiplatelet regimens. They stress the importance of shared decision-making between the patient and healthcare provider in the context of antiplatelet therapy management.

The correspondence from Almendro-Delia and colleagues advocates for ongoing, large-scale post-marketing surveillance and registry data analyses to capture real-world outcomes. They believe that such comprehensive data would elucidate the nuances of antiplatelet therapy cessation and facilitate the development of robust clinical guidelines tailored to diverse patient populations.

The debate regarding the safe discontinuation of antiplatelet agents like ticagrelor and clopidogrel will likely continue as new evidence emerges. The response by Dr. Almendro-Delia’s team in the Revista Española de Cardiología represents a critical commentary on current understanding and underscores the need for careful management and further investigation into this matter.

As this area of cardiology evolves, patients and clinicians alike must stay informed and actively engage in discussions regarding treatment choices, weighing the risks and benefits associated with the initiation, continuance, and cessation of these vital medications.

Keywords

1. Ticagrelor versus Clopidogrel
2. Antiplatelet Discontinuation Risks
3. Acute Coronary Syndromes Treatment
4. Percutaneous Coronary Intervention (PCI)
5. Platelet Aggregation Inhibitors Safety

References

1. Almendro-Delia, M., García-Rubira, J. C., & Hidalgo-Urbano, R. (2024). Risk of ticagrelor versus clopidogrel discontinuation. Response. Revista española de cardiología (English ed.). https://doi.org/10.1016/j.rec.2023.11.015
2. Wallentin, L., Becker, R. C., Budaj, A., Cannon, C. P., Emanuelsson, H., Held, C., … & Harrington, R. A. (2009). Ticagrelor versus clopidogrel in patients with acute coronary syndromes. New England Journal of Medicine, 361(11), 1045-1057.
3. Mehran, R., Baber, U., Steg, P. G., Ariti, C., Weisz, G., Witzenbichler, B., … & Kini, A. (2013). Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. The Lancet, 382(9906), 1714-1722.
4. Capodanno, D., & Angiolillo, D. J. (2016). Management of Antiplatelet Therapy in Patients With Coronary Artery Disease Requiring Cardiac and Noncardiac Surgery. Circulation, 134(13), 906-931.
5. Gurbel, P. A., Bliden, K. P., Butler, K., Tantry, U. S., Gesheff, T., Wei, C., … & Teng, R. (2009). Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation, 120(25), 2577-2585.