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Open research questions in Antiplatelet Therapy and Cardiovascular Diseases

42 unresolved questions extracted from the limitations and future-work sections of 390 Antiplatelet Therapy and Cardiovascular Diseases papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Conclusions The vast majority (86%) of the patients who experienced an off‐treatment recurrence after 28 months of rilonacept restarted interleukin‐1 pathway inhibition or corticosteroids, suggesting that NSAIDs/colchicine are insufficient in the management of patients with prolonged advanced disease.

    Multiyear Recurrent Pericarditis Disease Duration: Clinical Outcomes After Cessation of Long‐Term Interleukin‐1 Pathway Inhibition Provide Insights for Chronic Management · 2026 · DOI

  • N Engl J Med. 2025 N Engl J Med. 2025 ischemic risk Early aspirin discontinuation after 1 month may be reasonable in low-risk MI with complete revascularization using third-generation DES Immediate aspirin withdrawal (≤ 4 days) is not recommended Eur Heart J. 2026 J Am Coll Cardiol. 2025 ESC Congress 2025; Twice-daily aspirin should not be used routinely Twice-daily clopidogrel for 1 month may be considered as a cost-effective alternative to ticagrelor in selected STEMI patients IV cangrelor may be considered when oral absorption is unreliable TARGET-FIRST NEO-MINDSET ANDAMAN TADCLOT DAPT-SHOCK- AMI TOP-CABG Eur Heart J. 2025 TACSI N Engl J Med. 2025 TAILORED-CHIP Eur Heart J. 2026 PARTHENOPE AQUATIC J Am Coll Cardiol. 2025 N Engl J Med.

    Egyptian Society of Cardiology national advisory statement revisiting antiplatelet therapy: insights from E. S. C. 2025 hot-line trials · 2026 · DOI

  • However, the lipid benefit reflects only the overall analysis; the age-related subgroup differences are insufficient to guide clinical decisions due to lack of evidence, and should be considered hypothesis-generating findings only. Well-designed, large-sample, high-quality randomized controlled trials are warranted to further validate the long-term efficacy and safety of the combination therapy and to inform rational clinical use.

    Efficacy of Kuntai capsules with low-dose Femoston for perimenopausal syndrome: a meta-analysis · 2026 · DOI

  • Background Cytochrome P450 family two subfamily C member 19 (CYP2C19) loss-of-function (LOF) variants may influence clopidogrel response after percutaneous coronary intervention (PCI), but their prognostic relevance within combined clinical and procedural risk assessment remains incompletely defined.

    Risk factors for Post-PCI cardiovascular events in coronary artery disease patients treated with clopidogrel combined with aspirin · 2026 · DOI

  • Strengths Primary analysis restricted to RCTs; uniform 1-year follow-up; coverage of seven regimens; structured transferability assessment; multidimensional sensitivity analysis. Limitations (1) Regimens were not prospectively registered (PROSPERO), posing a risk of post-hoc analysis; (2) Sub- group analyses were exploratory (small sample size, sparse events) and serve only to generate hypotheses; (3) Mild heterogeneity in endpoint definitions (MACE components, bleeding criteria), but sensitivity analyses indicate robust conclusions; (4) A 1-year follow-up may be insufficient to capture the full potential benefit of DAPT on clinical hard endpoints; 5-year data from DACAB suggest a need for a longer observation window [35]; (5) The non-off-pump sub- group has an extremely small sample size, resulting in the highest uncertainty regarding related conclusions; interpre- tations should be most conservative.(6) Aspirin dose hetero- geneity. Aspirin doses varied across trials (75–300 mg/d), but formal dose-effect analysis was not feasible because dose variation was between-study (confounded with other study-level factors) and the number of trials using non-stan- dard doses was too small (n = 4) for meaningful subgroup or network analysis. All doses fell within guideline-recom- mended ranges (75–325 mg/d), and extensive sensitivity analyses confirmed the robustness of primary findings, indi- rectly indicating that dose heterogeneity did not introduce substantial bias.

    Time- and risk-dependent effects of dual antiplatelet therapy targeting the P2Y12 receptor after CABG: A network meta-analysis of graft permeability and clinical outcomes · 2026 · DOI

  • This study has strengths that include the capturing of data from a large multicenter cohort of nearly 10,000 patients with care spanning approximately 15 years at the largest integrated health care system within the United States, but our study is not without its limitations. First, as only medications admin- istered or prescriptions obtained from VA pharmacies were assessed, we did not determine whether veterans had received clopidogrel therapy outside the VA network. However, given that all included PVIs occurred within the VHA, although some durations may be misclassified, it is expected that especially early post-PVI clopidogrel, which is typically prescribed from the treating VAMC facility’s phar- macy on PVI discharge, has been sufficiently captured and JMCP.org | May 2026 | Vol. 32, No. 5 likely reflects true compliance with the CFU. Second, the available data cannot differentiate patient preferences and intolerance causing clopidogrel discontinuation. Additionally, the scope of this study was to observe gaps and heterogeneity in compliance to clopidogrel CFU but cannot specifically identify the provider characteristic or VAMC CFU implemen- tation strategies that were used. A qualitative assessment at local VAMC pharmacies to identify the techniques used and their association with compliance will be the focus of future work. Lastly, the data evaluating the association between post-PVI clopidogrel prescribing as well as CFU compliance and clinical outcomes are not available for analysis.

    Compliance with the Veterans Health Administration’s Pharmacy Benefit Management guidance for duration of clopidogrel following peripheral vascular interventions: a retrospective cohort study · 2026 · DOI

  • international largely guide CABG surgical techniques, perioperative management, and postoperative antiplatelet strategies, the predominance of enrolment from one centre may still limit the generalisability to other healthcare settings with differing patient characteristics, surgical practices, and perioperative management patterns. Sixthly, the trial was powered for the primary endpoint of SVG patency and may have been underpowered to detect differences in secondary clinical endpoints, particularly MACCE. These findings should therefore be interpreted as exploratory. Seventhly, our trial was not designed to identify patients for whom aspirin monotherapy was preferable; comparing a shortened DAPT strategy with aspirin alone represented a logical next step. Eighthly, although the non-inferiority margin was determined based on statistical preservation of effect considerations and expert consensus, it was not informed by empirical data on patient preference or established thresholds for minimal clinically important differences. Therefore, the selected margin may not represent a validated clinical threshold. Ninthly, the data and safety monitoring board review was conducted every six months. While no major safety concerns were identified during the trial, we acknowledge that a more frequent monitoring schedule would have aligned better with evolving standards for high risk surgical interventions, and a more geographically diverse and multi-institutional committee structure would further enhance independence. Tenthly, our security protocol relied on two stage authentication involving a mandatory virtual private network gateway followed by application level credentials. Although this security measure provides robust network isolation, we acknowledge that it does not constitute formal two factor authentication as defined by modern cybersecurity standards, representing a technical limitation. Eleventhly, a higher rate of infection events was observed in the 12 month DAPT group. However, our trial did not systematically collect data on baseline infection risk factors, duration of antibiotic treatment, or details of prophylactic antibiotic use, which limited our ability to adjust for these factors.

    Efficacy of dual antiplatelet therapy for three months versus 12 months after coronary artery bypass grafting: multicentre, double blinded, randomised controlled trial · 2026 · DOI

  • The references cite numerous mechanistic pathways (PKC, PI3K/Akt, aldose reductase, etc.) affecting diabetic platelets, but there is no synthesis of how these disparate mechanisms integrate or which are primary versus secondary effects.

    The Diabetic Platelet · 2022 · DOI

  • The excerpt is incomplete, ending mid-sentence regarding platelet sarcoplasmic endoplasmic reticulum Ca2+-ATPase and mu-calpain activity alterations in type 2 diabetes mellitus, leaving this comparison unfinished.

    The Diabetic Platelet · 2022 · DOI

  • Although a clinically meaningful effect of the interaction between PPIs and clopidogrel on cardiovascular outcomes has not been established, these studies provided the basis for recent changes in US Food and Drug Administration (FDA) labeling for several PPIs and clopidogrel.

    Proton-Pump Inhibitors in Patients Requiring Antiplatelet Therapy: New FDA Labeling · 2014 · DOI

  • This trial of aspirin for the primary prevention of cardiovascular disease demonstrates a conclusive reduction in the risk of myocardial infarction, but the evidence concerning stroke and total cardiovascular deaths remains inconclusive because of the inadequate numbers of physicians with these end points.

    Final Report on the Aspirin Component of the Ongoing Physicians' Health Study · 1989 · DOI

  • However, genetic test- ing does not account for non-genetic factors influencing platelet reactivity, such as diabetes, blood pressure, or drug-drug interac- tions.

    Cilostazol as an alternative to clopidogrel for secondary stroke prevention in patients with ischemic stroke and clopidogrel resistance: a retrospective study · 2026 · DOI

  • Rilonacept cessation and subsequent passive gradual washout is an evidence‐based pragmatic approach to determine if continued therapy is warranted to prevent subsequent recurrences.

    Multiyear Recurrent Pericarditis Disease Duration: Clinical Outcomes After Cessation of Long‐Term Interleukin‐1 Pathway Inhibition Provide Insights for Chronic Management · 2026 · DOI

  • Whether these distinct platelet inflammatory functions can be selectively suppressed to preserve hemostasis through the rational design of P2Y1R antagonists has not been explored.

    Discovery of a pathway-selective platelet P2Y1R inverse agonist that suppresses inflammation while preserving hemostasis · 2026 · DOI

  • (1,2) Despite identical guideline positioning, the optimal choice between the two agents has long remained unsettled, largely because head-to-head randomized data were scarce and the agents were assumed to be clinically interchangeable.

    Prasugrel vs. Ticagrelor: Can TUXEDO-2 Settle the Debate? · 2026 · DOI

  • This discrepancy may reflect differing release kinetics or sensitivity to anti- platelet agents, warranting further investigation.

    Plasma PF4 is a reliable biomarker of platelet reactivity and predictive of bleeding risk in DAPT patients undergoing cardiac surgery · 2026 · DOI

  • These findings support further investigation of the concept of genomic risk–guided aspirin therapy as a targeted strategy for primary prevention of ischemic stroke.

    Polygenic Risk Identifies Older Adults Who May Benefit From Aspirin for the Primary Prevention of Ischemic Stroke · 2026 · DOI

  • Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.

    Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke · 2024 · DOI

  • Multiple studies examine platelet hyperreactivity in diabetes, but the excerpt lacks discussion of whether interventions targeting specific molecular pathways consistently reduce platelet dysfunction across patient populations.

    The Diabetic Platelet · 2022 · DOI

  • In order to maintain the patency of the coronary arteries and graft conduits, various antithrombotic protocols have been introduced over the years, combining various antiplatelet and anticoagulant drugs, but still there is no consensus.

    Antithrombotic regimens in patients after coronary artery bypass grafting and coronary endarterectomy · 2020 · DOI

  • Finally, we comment on the pharmacogenetics of other cardiovascular drugs that have been extensively studied, but for which data are conflicting or that have not yet seen clinical implementation.

    The Pharmacogenetics of Cardiovascular Drugs / FARMAKOGENETIKA KARDIOVASKULARNIH LEKOVA · 2013 · DOI

  • Although the use of anticoagulants in dental extractions is highly protocolized, a clear control method has not yet been established for antiplatelet drugs.

    Dental extractions in patients on antiplatelet therapy. A study conducted by the Oral Health Department of the Navarre Health Service (Spain) · 2009 · DOI

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42 open questions have been extracted from the limitations and future-work passages of 390 Antiplatelet Therapy and Cardiovascular Diseases papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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