ACHAIKI IATRIKI | 2024; 43(4):195–204
Review
Amalia Papanikolaou1, Anastasios Apostolos1,2, David-Dimitris Chlorogiannis3, Angelos Kramvis1, Filippos Timpilis1, Anastasia Latta1, Kassiani Maria Nastouli1, Dimitra Tzegka1, Kornilia Pepa1, Athanasia Maria Georga1, Fotis Kallinikos1, Maria Bozika1, Michaela Routoula1, Stella Ruzi1, Vassiliki Fotopoulou1, Antonis Karanasos1, Michail I. Papafaklis1, Periklis Davlouros1, Grigorios Tsigkas1
1Department of Cardiology, University Hospital of Patras, Patras, Greece
2First Department of Cardiology, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
3Department of Radiology, Brigham and Women’s Hospital, Boston, USA.
Received: 28 Feb 2024; Accepted: 25 Jun 2024
Corresponding author: Grigorios Tsigkas, Department of Cardiology, University Hospital of Patras, 265 04 Patras, Greece, E-mail: gregtsig@hotmail.com
Key words: DAPT, dual antiplatelet therapy, PCI
Abstract
The optimal duration of Dual Antiplatelet Therapy (DAPT) following Percutaneous Coronary Intervention (PCI) remains a topic of significant debate and investigation. This review examines the rationale for DAPT shortening duration in specific populations. We discuss the challenges associated with balancing ischemic and bleeding risks in patients undergoing PCI, highlighting the importance of tailored treatment approaches based on individualized risk profiles. Furthermore, we delve into the evidence supporting abbreviated DAPT in high-risk patient cohorts, including those with increased bleeding risk, comorbid malignancies, diabetes mellitus, and complex coronary artery disease. Emerging data suggest that abbreviated DAPT regimens offer comparable efficacy in preventing thrombotic events while reducing bleeding complications. In conclusion, the ongoing evolution of DAPT underscores the need for evidence-based, patient-centered approaches to optimize outcomes for patients undergoing PCI.
INTRODUCTION
The administration of antiplatelet treatment is a crucial element in managing patients undergoing Percutaneous Coronary Intervention (PCI) for Chronic Coronary Syndromes (CCS) or Acute Coronary Syndromes (ACS), aimed at preventing stent thrombosis, restenosis and adverse events, like myocardial infarction or ischemic stroke. Optimal therapeutic strategies, including the selection, combination, timing, and duration of therapy, require meticulous evaluation of various patient and procedural factors. Treatment decisions should carefully balance the benefits of antithrombotic therapy against the potential for severe and/or life-threatening bleeding [1].
According to the current guidelines of the European Society of Cardiology (ESC), DAPT is recommended as the standard for 6 months for patients with CCS and for 12 months following an ACS. However, this duration may be extended for high-ischemic risk patients and shortened for those at high risk of bleeding [2-3].
In recent years, the optimal duration of DAPT has provoked significant controversy and debate. Numerous Randomized Control Trials (RCTs) and meta-analyses have suggested alternative treatment approaches for patients with CCS or ACS. These proposals entail shortening the duration of DAPT to one-three or three–six months after PCI and transitioning to P2Y12 monotherapy as a form of de-escalation [4].
This review intends to provide a comprehensive overview of the existing evidence regarding abbreviated DAPT duration with a focus on the management of patients with specific comorbidities, anatomical and technical issues during PCI.
Why is DAPT Shortening important?
The ongoing advancements in stent technologies, coupled with the introduction of novel antiplatelet agents, and the broadening of indications to encompass an aging and medically complex population with anatomically intricate coronary artery disease (CAD), present formidable challenges in the management of patients undergoing percutaneous coronary interventions even in 2024 [5].
The delicate balance between high-risk factors for bleeding and thrombosis comprises a daily clinical dilemma. Both the thrombotic and the hemorrhagic risk are higher during the first months after PCI, thereafter they decrease and remain relatively stable over time [6]. Moreover, major bleeding impacts on mortality comparably to or exceeding that of major ischemic events. On the other hand, minor bleeding incidents may lead to unplanned cessation of antiplatelet therapy, potentially resulting in an increased occurrence of ischemic events. Hence, patients at high bleeding risk may benefit from modifying either the components or the duration of DAPT. Among the strategies investigated to mitigate bleeding events, shortening the duration of DAPT has been the most extensively studied approach [7].
Another issue that may be addressed by the shortening of DAPT duration is patient compliance to long-term medication regimens. Non-adherence rates for post-myocardial infarction patients are recorded to range from 13% to 60% for prescribed, evidence-based medications [8]. Noncompliance to DAPT medication as a secondary prevention strategy, after percutaneous coronary intervention has been reported to be the strongest independent predictor for stent thrombosis [9], as a quadruplicate incidence of a recurrent event (11.0% vs 2.8%; P=0.044) and duplicate hospitalization rates (21.2% vs 9.9%; P=0.04) have been demonstrated. Premature cessation of dual antiplatelet therapy might be not only influenced by the drugs adverse effects, such as bleeding, dyspnea, or gastrointestinal symptoms but also by psychological factors such as depression and anxiety, which could be potentially linked to the complications associated with coronary artery disease [10-11].
Lastly, abbreviated DAPT may reduce the duration of polypharmacy, a very common condition for people suffering from CAD, because apart from the multiple medications that are necessary for secondary prevention such as antiplatelet, antihypertensive, hypolipidemic drugs etc., many of these patients suffer concomitantly from additional comorbid conditions. Except for the extensive costs in all healthcare systems, polypharmacy elevates the likelihood of inappropriate medication utilization and is associated with higher hospitalization and mortality rates [12].
Current evidence supporting the abbreviation of DAPT
A. General Population
The development of newer generations of drug-eluting stents (DES) with refined antiproliferative agents and reduced strut thickness has resulted in decreased stent thrombosis rates while maintaining low restenosis rates. Additionally, more potent P2Y12 inhibitors such as prasugrel and ticagrelor have emerged as viable options for single antiplatelet therapy. Furthermore, the use of intravascular imaging has contributed to advancements in intervention techniques [13].
Consequently, several randomized controlled trials have been conducted to assess the safety of reducing the duration of dual antiplatelet therapy compared to standard duration. Recently, various meta-analyses of the largest published randomized controlled trials comparing abbreviated (one–three months) DAPT with standard-term (six–twelve months) DAPT in patients undergoing percutaneous coronary intervention with DES for both acute and chronic coronary syndromes have been conducted. They all concluded that one–three-month DAPT reduces major bleeding without increasing ischemic events compared to longer DAPT durations, thus providing a better risk-benefit profile. However, further research is necessary to determine the optimal single antiplatelet agent after one-three months of DAPT [14-16]. These results came to be verified by the SHARE trial, a multicenter RCT that was last month published and investigated a composite of major bleeding and major adverse cardiac and cerebrovascular events between three and twelve months DAPT after the index PCI.
Correct identification and risk stratification of patients with characteristics of high ischemic or high bleeding risk are crucial, as this subgroup stands to benefit the most from tailored DAPT (Table 1).
B. Shortening DAPT in patients at elevated risk of bleeding
In routine clinical practice up to 40% of individuals undergoing percutaneous coronary intervention are classified as patients at high bleeding risk (HBR). However, this intricate population is frequently excluded or inadequately represented in trials addressing the management of patients post-PCI [17]. Recently, the Academic Research Consortium for High Bleeding Risk (ARC- HBR) developed a consensus definition of patients at high bleeding risk based on the published evidence [18]. Factors associated with an elevated hemorrhagic risk include age over 75 years, chronic kidney disease, use of oral anticoagulation, anemia, moderate thrombocytopenia, liver cirrhosis with portal hypertension, active malignancy, chronic bleeding diathesis, spontaneous bleeding requiring hospitalization or transfusion, intracranial bleeding, long-term use of oral NSAIDs or steroids, recent major surgery, or surgery under DAPT (Figure 1).
Figure 1. High Bleeding/ Ischemic Patient Characteristics and ESC Guidelines recommendations on DAPT.
Hb: Hemoglobin, GFR: Glomerular Filtration Rate, PLTs: Platelets, PH: Portal Hypertension, ICH: Intracranial Hemorrhage, PCI: Percutaneous Coronary Intervention, DAPT: Dual Antiplatelet Therapy, ACS: Acute Coronary Syndrome, SCAD: Stable Coronary Artery Disease, PAD: Peripheral Arterial Disease, CAD: Coronary Artery Disease.
In patients presenting such characteristics, given the ability of new generation stents to heal rapidly, extending DAPT over one-three months might be unnecessary [19]. In the last years, numerous registries have investigated this scenario. Recently, Costa et al., in a recent meta-analysis of eleven trials and 9006 patients compared the outcomes of very short (one month) or short (three months) with standard (≥six months) DAPT duration in HBR patients. Abbreviated DAPT reduced major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%) and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. Moreover, no difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed [20].
These findings reinforce the safety and efficacy of abbreviated DAPT in patients classified as high bleeding risk, advocating its inclusion as a potential treatment strategy.
C. Shortening DAPT in patients at elevated risk of ischemia
The recent ESC guidelines recommend a definition for patients at high or moderate thrombotic risk to aid in stratifying thrombotic risk and guiding intensified antithrombotic treatment following the standard duration of dual antiplatelet therapy. These categories encompass individuals with complex coronary artery disease, diabetes mellitus (DM), recurrent myocardial infarction, premature or accelerated CAD, concomitant peripheral arterial disease, or systemic inflammatory disease [17-18]. In addition, technical aspects such as the implantation of at least three stents, a total stent length of 60mm or more, complex revascularization, or stent thrombosis during antiplatelet therapy are considered in these recommendations (Figure 1).
In the following paragraphs, we will also discuss the management of specific populations of individuals who are at an elevated risk of ischemia.
Tailoring DAPT for Specific Patient Population
A. DAPT after PCI in patients with Diabetes Mellitus
Worldwide, greater than 30% of individuals with diabetes concurrently experience cardiovascular disease, which is responsible for approximately half of all deaths [21]. This phenomenon may be potentially attributed to the presence of multifocal coronary artery lesions, which is often observed in these patients, as well as their increased susceptibility to stent restenosis [22]. Furthermore, resistance to antiplatelet therapy has been observed in these patients [23].
According to current guidelines, DAPT post-percutaneous coronary intervention in diabetic patients is recommended for a duration ranging from three to twelve months. However, the duration may be extended up to 30 months based on the physician’s clinical judgment [2-3].
A systematic review and meta-analysis by Gargiulo et al., which included 11,473 participants, investigated the clinical outcomes of short-term (≤six months) versus long-term (twelve months) dual antiplatelet therapy following PCI in patients with and without diabetes. The findings indicated that although diabetes was identified as an independent predictor of major adverse cardiac events (MACE) (HR 2.30, 95% CI 1.01-5.27; P=0.048), long-term DAPT did not reduce the risk of MACE but instead increased the risk of bleeding among patients with stents, regardless of diabetes status [24].
Besides, a recent meta-analysis involving eight studies, and 12,665 participants observed that the implementation of dual antiplatelet therapy for ≤three months (S-DAPT) in diabetic patients led to a 17% reduction in the risk of net adverse clinical events (NACE) compared to standard-duration DAPT (RR: 0.83, 95% CI; 0.72–0.96). These findings suggest that S-DAPT could represent a safe treatment option for diabetic patients. Interestingly, the analysis indicated that ticagrelor-based S-DAPT was linked with decreased mortality rates [25].
On the contrary, Grodzinsky et al., conducted a study using a real-world PCI registry comprising 2334 patients from 10 hospitals in the USA focusing on bleeding risk in patients with DM, that have been prescribed DAPT following PCI. Their findings indicated that diabetic patients experienced fewer bleeding events during the 1-year follow-up period post- DAPT (RR 0.89, 95% CI 0.83-0.96) compared to non-diabetic patients. Consequently, they concluded that prolonging dual antiplatelet regimen might be advantageous for diabetic patients, considering their heightened ischemic risk [26].
B. DAPT after Complex- PCI
“Complex” PCI, despite the lack of a universal definition, refers to percutaneous coronary intervention procedures that involve challenging anatomical features, such as multiple lesions, heavily calcified lesions, chronic total occlusions, bifurcation lesions, or lesions in small vessels. These complicated interventions encompass more than 30% of the total PCI procedures and often require advanced techniques and specialized equipment to achieve successful outcomes. For this reason, patients undergoing complex PCI face an elevated likelihood of experiencing adverse events, such as mortality, myocardial infarction, and stent thrombosis. Therefore, antithrombotic therapy plays a role in partially mitigating these risks [27-28].
Angelo et al., conducted a meta-analysis involving 31,627 patients across 5 trials, of whom 8,328 (26.3%) underwent complex PCI. Their study aimed to assess the efficacy and safety of short DAPT (one-three months) compared to standard DAPT (≥twelve months) based on PCI complexity. The authors concluded that patients undergoing complex PCI may experience greater benefit and fewer adverse events from P2Y12 inhibitor monotherapy following early aspirin withdrawal compared to standard DAPT. They found that P2Y12 inhibitor monotherapy, in comparison to standard DAPT, was associated with similar outcomes of all-cause death, stent thrombosis, and stroke, with no observed interaction between complex and noncomplex PCI. However, they noted a reduced risk of myocardial infarction in complex PCI (HR 0.77, 95% CI 0.60-0.99, P = 0.042), as well as a significantly decreased incidence of major bleeding events (HR 0.67, 95% CI 0.49-0.91, P = 0.010) with the strategy of short DAPT [29].
Furthermore, Apostolos et al., conducted another recent meta-analysis involving 6275 individuals to investigate the safety and efficacy of a one-month DAPT regimen compared to a longer duration following complex PCI. The study found that shortening DAPT to 30 days after complex PCI did not result in an increased risk of net adverse clinical events (OR: 0.77, 95% CI: 0.52–1.14) or major adverse cardiac events (including mortality, myocardial infarctions, stroke, or stent thrombosis). Additionally, although there was a reduction in pooled incidence of major bleeding, this finding did not reach statistical significance [30].
The established correlation between abbreviated dual antiplatelet therapy and a reduced incidence of major bleeding events, without a corresponding increase in mortality or ischemic events, is reinforced by advancements in biotechnology [13]. These advancements include the development of drug-eluting stents approved for shortening DAPT to 1 month. Additionally, the increasing use and advancements in intravascular imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have improved the optimization of percutaneous coronary intervention procedures [31]. Therefore, even in cases of high PCI complexity, abbreviating DAPT may be safe, but optimizing procedures through appropriate imaging and functional tests remains crucial.
C. DAPT following PCI in patients with malignancies
Patients on dual antiplatelet therapy due to CAD who also have comorbid cancer represent a complex subgroup of individuals with an elevated risk of bleeding and ischemia. This subset, estimated to encompass up to 15% of acute coronary syndrome patients, adds further intricacy to the complexity of post PCI pharmacological management [32].
Research has shown that readmissions due to acute myocardial infarction within 90 days post-PCI are more frequent in patients with comorbid malignancies (12.1% in lung, 10.8% in colon, 7.5% in breast, 7.0% in prostate, and 9.1% overall). Correspondingly, the rate of rehospitalization due to bleeding is also elevated (4.2% in colon, 1.5% in lung, 1.4% in prostate, 0.6% in breast, and 1.6% overall) [33]. The above-mentioned rates may be attributed to the fact that cancer patients present with numerous intricate characteristics. In addition to common cancer-related adverse events such as coagulopathy and anemia, chemotherapy and radiotherapy can induce prothrombotic, vasospastic, and proinflammatory effects in the vasculature. Moreover, the potential for cancer recurrence may necessitate interruptions in DAPT for procedures such as biopsies, surgeries, or resumption of cancer treatment [34-35]. In summary, these factors collectively contribute to the challenges involved in managing patients with both malignancies and coronary artery disease.
According to the 2022 ESC Guidelines on cardio-oncology, the duration of DAPT should be as short as possible, with 1–3 months clopidogrel based DAPT in patients with a platelet count of over 30,000/Μl being proposed as the optimal therapeutic regimen. Besides, the Academic Research Consortium for high bleeding risk recently established a one-month duration of DAPT as the optimal post- PCI duration for patients with active cancer (excluding non-melanoma skin cancer) and a high risk of bleeding. Additionally, a three-month duration of DAPT is recommended for cancer patients deemed non-high risk. In cases of acute coronary syndrome with an elevated risk of ischemia, an extension of DAPT to six months is advised [36].
Finally, the initiation of OCT imaging may help guide discontinuation of DAPT. This is because risk factors for stent thrombosis, such as stent malposition, incomplete strut coverage, and in-stent restenosis, may be visualized. Consequently, low-risk patients who can safely discontinue DAPT and proceed with essential cancer-related surgeries or procedures can be identified [37].
Overall, in this vulnerable patient population, a tailored and multidisciplinary approach is paramount to enhance both life expectancy and quality of life for patients.
Future Perspectives
The optimal duration of dual antiplatelet therapy and the most effective agent for subsequent monotherapy have been subjects of recent scrutiny in clinical studies. Following encouraging outcomes from studies advocating for shortened DAPT durations, with subsequent administration of a P2Y12 inhibitor alone, interest has grown in exploring the complete omission of aspirin immediately after percutaneous coronary intervention. The recently published ASET trial [38], a pilot investigation conducted by Kogame et al., examined the safety and feasibility of prasugrel monotherapy following successful everolimus-eluting stent implantation in a carefully selected cohort of patients with low anatomic complexity and stable coronary artery disease. The study yielded positive results, prompting the initiation of larger RCTs to further evaluate this treatment approach. Furthermore, the long-awaited STOP-DAPT-3 trial [39] was recently published, comparing single low-dose prasugrel to the standard DAPT strategy in patients post-PCI following an acute coronary syndrome or those at high risk of bleeding. However, the trial’s no aspirin strategy failed to reduce major bleeding within 1 month and showed an increased risk of coronary events. Consequently, the ongoing NEO-MINDSET study (NCT04360720) holds promise to provide additional insights into this innovative treatment strategy and elucidate its potential for clinical application [40]. Finally, the T-PASS trial, which focused on ACS patients treated with new-generation bioresorbable polymer sirolimus-eluting stents (BP-SES), demonstrated that a short-term DAPT strategy of less than one month followed by ticagrelor monotherapy was both non inferior and superior to the conventional twelve-month ticagrelor-based DAPT regimen. This superiority was evidenced by a significant reduction in bleeding complications in the short-term DAPT group, while the risk of major adverse cardiac and cerebrovascular events remained similar between the two groups [41]
A significant revolution in the field of DAPT may be on the horizon with the introduction of several new antiplatelet agents. Among these agents currently under clinical development for use in patients undergoing PCI are selatogrel, a reversible non-thienopyridine P2Y12 receptor antagonist administered subcutaneously [42]; revacept, an intravenously administered inhibitor of GPVI, the major platelet collagen receptor [43]; and RUC-4, a GPIIb/IIIa inhibitor with a novel mechanism of action designed for intramuscular administration [44]. These innovative antiplatelet agents hold great promise for improving outcomes and reducing complications in patients undergoing PCI.
CONCLUSION
In conclusion, the future of DAPT lies in its continued evolution, driven by advancements in medical science and technology, as well as a deeper understanding of patient-specific factors. By embracing evidence-based approaches and innovation, clinicians can optimize treatment strategies and ultimately improve the prognosis and quality of life for patients undergoing PCI.
Conflict of Interest: None to declare.
Declaration of funding sources: None to declare.
Author Contribution: All authors have contributed substantially to the work as follows: Conceptualization, A.P and G.T.; methodology, A.P , AA and A.K.(Angelos Kramvis); writing- original draft preparation, A.P. and A.K (Angelos Kramvis); writing- review and editing, A.P., A.A., D-D.C., A.K.(Angelos Kramvis), F.T., A.L., K.M.N., D.T., K.P., A.G., F.K., M.B., M.R., S.R., V.F., G.T.; supervision, A.K.(Antonis Karanasos), M.P., P.D., G.T. All authors have read and agreed to the published version of the manuscript.
REFERENCES
- Hudzik B, Błachut A, Lesiak M, Kubica J, Wojakowski W, Gąsior M. Summary of the European Society of Cardiology guidelines on dual antiplatelet therapy in patients after percutaneous coronary interventions. Kardiol Pol. 2022;80(10):974-89.
- Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-6.
- Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-77.
- Aslam Zahid MB, Memon MS, Tappiti M, Shantha Kumar V, Nazir AM, Koganti B, et al. Duration of Dual Antiplatelet Therapy After Stent Implantation, Still an Enigma: A Systematic Review of Randomized Clinical Trials. Cureus. 2021;13(11): e19549
- Capodanno D, Bhatt DL, Gibson CM, James S, Kimura T, Mehran R, et al. Bleeding avoidance strategies in percutaneous coronary intervention. Nat Rev Cardiol. 2022;19(2):117-132.
- Angiolillo DJ, Galli M, Collet JP, Kastrati A, O’Donoghue ML. Antiplatelet therapy after percutaneous coronary intervention. EuroIntervention. 2022;17(17):e1371-96.
- Kosobucka A, Michalski P, Pietrzykowski Ł, Kasprzak M, Obońska K, Fabiszak T, et al. Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction. Patient Prefer Adherence. 2018;12:333-40.
- Kubica A, Obońska K, Kasprzak M, Sztuba B, Navarese EP, Koziński M, et al. Prediction of high risk of non-adherence to antiplatelet treatment. Kardiol Pol. 2016;74(1):61-7.
- De Servi S, Roncella A, Reimers B. Causes and clinical implications of premature discontinuation of dual antiplatelet therapy. Curr Opin Cardiol. 2011;26 (Suppl 1):S15-21.
- Zanchin T, Temperli F, Karagiannis A, Zanchin C, Räsänen M, Koskinas KC, et al. Frequency, Reasons, and Impact of Premature Ticagrelor Discontinuation in Patients Undergoing Coronary Revascularization in Routine Clinical Practice: Results From the Bern Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv. 2018;11(5):e006132.
- Frazier SC. Health outcomes and polypharmacy in elderly individuals: an integrated literature review. J Gerontol Nurs. 2005;31(9):4-11.
- Johansson T, Abuzahra ME, Keller S, Mann E, Faller B, Sommerauer C, et al. Impact of strategies to reduce polypharmacy on clinically relevant endpoints: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(2):532-48.
- Apostolos A, Vasilagkos G, Toutouzas K, Tsigkas G. DAPT Shortening After Complex PCI: Examining the Fine Print. J Am Coll Cardiol. 2023;81(22):e191.
- Rout A, Sharma A, Ikram S, Garg A. Short-term dual antiplatelet therapy for 1-3 months after percutaneous coronary intervention using drug eluting stents: A systematic review and meta-analysis of randomized clinical trials. Catheter Cardiovasc Interv. 2023;101(2):299-307.
- Park DY, An S, Kumar A, Malhotra S, Jolly N, Kaur A, et al. Abbreviated versus Standard Duration of DAPT after PCI: A Systematic Review and Network Meta-analysis. Am J Cardiovasc Drugs. 2022;22(6):633-45.
- Tsigkas G, Apostolos A, Chlorogiannis DD, Bousoula E, Vasilagkos G, Tsalamandris S, et al. Thirty-Days versus Longer Duration of Dual Antiplatelet Treatment after Percutaneous Coronary Interventions with Newer Drug-Eluting Stents: A Systematic Review and Meta-Analysis. Life (Basel). 2023;13(3):666.
- Ueki Y, Bär S, Losdat S, Otsuka T, Zanchin C, Zanchin T, et al. Validation of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in patients undergoing percutaneous coronary intervention and comparison with contemporary bleeding risk scores. EuroIntervention. 2020;16(5):371-9.
- Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019;40(31):2632-53.
- Capodanno D, Greco A. Dual antiplatelet therapy in patients at high bleeding risk: less is more-more or less. Eur Heart J. 2023 Mar;44(11):969-71.
- Costa F, Montalto C, Branca M, Hong SJ, Watanabe H, Franzone A, et al. Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials. Eur Heart J. 2023;44(11):954-68.
- Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17(1):83.
- Wilson S, Mone P, Kansakar U, Jankauskas SS, Donkor K, Adebayo A, et al. Diabetes and restenosis. Cardiovasc Diabetol. 2022;21(1):23.
- Ajjan R, Storey RF, Grant PJ. Aspirin resistance and diabetes mellitus. Diabetologia. 2008;51(3):385-90.
- Gargiulo G, Windecker S, da Costa BR, Feres F, Hong MK, Gilard M, et al. Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials. BMJ. 2016;355:i5483.
- Apostolos A, Travlos C, Tsioulos G, Chlorogiannis DD, Karanasos A, Papafaklis M, et al. Duration of Dual Antiplatelet Treatment After Percutaneous Coronary Intervention in Patients With Diabetes: A Systematic Review and Meta-analysis. J Cardiovasc Pharmacol. 2024;83(1):64-72.
- Grodzinsky A, Arnold SV, Wang TY, Sharma P, Gosch K, Jones PG, et al. Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy. Am Heart J. 2016;182:111-118.
- Iftikhar SF, Bishop MA, Hu P. Complex Coronary Artery Lesions. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
- Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2018;53(1):34-78
- Oliva A, Castiello DS, Franzone A, Condorelli G, Colombo A, Esposito G, et al. P2Y12 Inhibitors Monotherapy in Patients Undergoing Complex vs Non-Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials. Am Heart J. 2023;255:71-81.
- Apostolos A, Chlorogiannis, DD, Chrysostomidis G, Bozika M, Timpilis F, Kramvis A, et al. Efficacy and Safety of Thirty-Day Dual-Antiplatelet Therapy Following Complex Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis. 2024;11(2):43
- Apostolos A, Chlorogiannis D, Vasilagkos G, Katsanos K, Toutouzas K, Aminian A, et al. Safety and efficacy of shortened dual antiplatelet therapy after complex percutaneous coronary intervention: A systematic review and meta-analysis. Hellenic J Cardiol. 2023;71:33-41.
- Radmilovic J, Di Vilio A, D’Andrea A, Pastore F, Forni A, Desiderio A, et al. The Pharmacological Approach to Oncologic Patients with Acute Coronary Syndrome. J Clin Med. 2020;9(12):3926.
- Kwok CS, Wong CW, Kontopantelis E, Barac A, Brown SA, Velagapudi P, et al. Percutaneous coronary intervention in patients with cancer and readmissions within 90 days for acute myocardial infarction and bleeding in the USA. Eur Heart J. 2021;42(10):1019-34.
- Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013;11(2):223-33.
- de Boer RA, Meijers WC, van der Meer P, van Veldhuisen DJ. Cancer and heart disease: associations and relations. Eur J Heart Fail. 2019;21(12):1515-25.
- Tsigkas G, Vakka A, Apostolos A, Bousoula E, Vythoulkas-Biotis N, Koufou EE, et al. Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review. J Cardiovasc Dev Dis. 2023;10(4):135.
- Iliescu CA, Cilingiroglu M, Giza DE, Rosales O, Lebeau J, Guerrero-Mantilla I, et al. “Bringing on the light” in a complex clinical scenario: Optical coherence tomography-guided discontinuation of antiplatelet therapy in cancer patients with coronary artery disease (PROTECT-OCT registry). Am Heart J. 2017;194:83-91.
- Kogame N, Guimarães PO, Modolo R, De Martino F, Tinoco J, Ribeiro EE, et al. Aspirin-Free Prasugrel Monotherapy Following Coronary Artery Stenting in Patients With Stable CAD: The ASET Pilot Study. JACC Cardiovasc Interv. 2020;13(19):2251-2262.
- Natsuaki M, Watanabe H, Morimoto T, Yamamoto K, Obayashi Y, Nishikawa R, et al. An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial. Circulation. 2023;149(8):585–600
- Guimarães PO, Franken M, Tavares CAM, Silveira FS, Antunes MO, Bergo RR, et al. P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial. EuroIntervention. 2023 Jul 17;19(4):e323- 9.
- Hong SJ, Lee SJ, Suh Y, Yun KH, Kang TS, Shin S, et al. T-PASS (Ticagrelor Monotherapy in Patients Treated With New-Generation Drug-Eluting Stents for Acute Coronary Syndrome) Investigators. Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial. Circulation. 2024;149(8):562-73
- Beavers CJ, Effoe SA, Dobesh PP. Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor. J Cardiovasc Pharmacol. 2022;79(2):161-7.
- Mayer K, Hein-Rothweiler R, Schüpke S, Janisch M, Bernlochner I, Ndrepepa G, et al. Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial. JAMA Cardiol. 2021;6(7):753-61.
- Li J, Vootukuri S, Shang Y, Negri A, Jiang JK, Nedelman M, et al. RUC-4: a novel αIIbβ3 antagonist for prehospital therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2014;34(10):2321-9.
- Hong SJ, Kim JS, Hong SJ, Lim DS, Lee SY, Yun KH, 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):1801-11.
- De Luca G, Damen SA, Camaro C, Benit E, Verdoia M, Rasoul S, et al. Final results of the randomised evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with a new-generation stent (REDUCE trial). EuroIntervention. 2019;15(11):e990-8.
- Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, et al. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020;323(23):2407-16.
- Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019;381(21):2032-42.
- Valgimigli M, Frigoli E, Heg D, Tijssen J, Jüni P, Vranckx P, et al. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021;385(18):1643-55.
- Hahn JY, Song YB, Oh JH, Chun WJ, Park YH, Jang WJ, et al. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial. JAMA. 2019;321(24):2428-37.
- Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018;392(10151):940-9.
- Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Ogita M, et al. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial. JAMA Cardiol. 2022;7(4):407-17.
- Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Nishikawa R, et al. Clopidogrel vs Aspirin Monotherapy Beyond 1 Year After Percutaneous Coronary Intervention. J Am Coll Cardiol. 2024;83(1):17-31.
- Franzone A, McFadden E, Leonardi S, Piccolo R, Vranckx P, Serruys PW, et al. Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting. J Am Coll Cardiol. 2019;74(18):2223-34.
- Baber U, Dangas G, Angiolillo DJ, Cohen DJ, Sharma SK, Nicolas J, et al. Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS. Eur Heart J. 2020;41(37):3533-45.
- van Geuns RJ, Chun-Chin C, McEntegart MB, Merkulov E, Kretov E, Lesiak M, et al. Bioabsorbable polymer drug-eluting stents with 4-month dual antiplatelet therapy versus durable polymer drug-eluting stents with 12-month dual antiplatelet therapy in patients with left main coronary artery disease: the IDEAL-LM randomised trial. EuroIntervention. 2022;17(18):1467-76.
- Escaned J, Cao D, Baber U, Nicolas J, Sartori S, Zhang Z, et al. Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR. Eur Heart J. 2021;42(45):4624-34.
- Han JK, Hwang D, Yang S, Park SH, Kang J, Yang HM, et al. Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial. Circulation. 2023 May 2;147(18):1358-68.
- Min PK, Kang TS, Cho YH, Cheong SS, Kim BK, Kwon SW, et al. P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial. JAMA Netw Open. 2024;7(3):e240877.