Jul 2026· Journal of Basic and Clinical Physiology and Pharmacology· 0 citations· 146 references
Medicine
TL;DR
Evidence suggests that genotype-guided therapy, PFT-guided treatment, and individualized DAPT duration may improve the balance between ischemic protection and bleeding risk in selected high-risk populations, but routine implementation remains limited by inconsistent clinical outcome benefits.
Abstract
Abstract Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 inhibitor, remains central to secondary prevention after acute coronary syndrome and percutaneous coronary intervention. However, substantial interindividual variability in antiplatelet response, particularly clopidogrel resistance associated with CYP2C19 polymorphisms, has challenged the conventional “one-size-fits-all” approach and increased interest in precision-guided antiplatelet strategies. This narrative review synthesized literature identified through PubMed, Scopus, Web of Science, and Google Scholar, focusing on randomized trials, genotype-guided studies, platelet function testing (PFT), meta-analyses, guideline statements, and emerging artificial intelligence (AI)-based prediction models. Evidence suggests that genotype-guided therapy, PFT-guided treatment, and individualized DAPT duration may improve the balance between ischemic protection and bleeding risk in selected high-risk populations. However, routine implementation remains limited by inconsistent clinical outcome benefits, heterogeneous testing strategies, modest risk-score performance, cost, infrastructure barriers, and variable guideline recommendations. Precision-guided DAPT is promising, but broader adoption requires stronger prospective evidence, standardized testing pathways, and real-world validation.
Introduction Dual antiplatelet therapy (DAPT) is standard after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS), but prolonged DAPT increases bleeding risk, particularly in East Asian and high bleeding-risk (HBR) populations. De‑escalation strategies aim to balance ischaemic and bleeding risks. Methods We conducted a structured literature search in PubMed, EMBASE, and the Cochrane Library (January 2018–April 2026) for randomized trials and key studies on DAPT de-escalation in ACS patients after PCI, using the Academic Research Consortium (ARC) tripartite classification framework. Results Strong evidence supports discontinuation-based strategies: 3-month (TICO, TWILIGHT, SMART-CHOICE) and 1-month (ULTIMATE-DAPT, T-PASS, TARGET-FIRST) DAPT followed by P2Y12 inhibitor monotherapy reduce bleeding without increasing ischaemic events in selected patients. MASTER-DAPT established 1-month DAPT safety in HBR patients. However, very early aspirin withdrawal (within 4 days, NEO-MINDSET) failed non-inferiority for ischaemic outcomes, and clopidogrel monotherapy after 1-month DAPT was associated with higher ischaemic risk (STOPDAPT-2 ACS). Drug‑intensity de-escalation (e.g., ticagrelor-to-clopidogrel switching) and guided strategies using genotyping or platelet‑function testing show promise but require further validation. Conclusion Individualized DAPT de-escalation, guided by dynamic risk assessment using PRECISE‑DAPT and ARC-HBR criteria, optimizes net clinical benefit. Ticagrelor monotherapy after at least 1 month of DAPT is preferred over clopidogrel in ACS. Future research should focus on precision antithrombotic strategies in Chinese populations and high‑risk subgroups.
Antithrombotic therapy after percutaneous coronary intervention (PCI) is shifting from fixed 12-month dual antiplatelet therapy (DAPT) to risk-stratified, patient-centered regimens. In this systematic review (80 studies; >330,000 patients), we compare personalized versus fixed DAPT strategies, evaluate abbreviated DAPT in high-bleeding-risk (HBR) populations, and evaluate bleeding and ischemic risk scores. Personalized strategies, including genotype-guided therapy, ultra-short DAPT (≤1 month) with P2Y12 monotherapy, and 3-month DAPT, substantially reduce bleeding (often by roughly 25%-65%); ischemic risk after de-escalation is heterogeneous across populations and strategies, with most trials showing neutrality and one (STOPDAPT-2 ACS) signaling increased myocardial infarction (MI) when aspirin was withdrawn after 1-2 months of clopidogrel-based DAPT in acute coronary syndrome (ACS). In HBR patients, 1 to 3-month DAPT followed by P2Y12 monotherapy lowers major bleeding by up to 65% and may reduce cardiovascular mortality, without increased MI or stent thrombosis in most trials, although ischemic signals varied by population and strategy. In atrial fibrillation, avoiding prolonged triple therapy reduces bleeding by approximately 30%. In ACS, prasugrel is favored over ticagrelor for ischemic outcomes; ARC-HBR, PRECISE-DAPT, and the newer PRECISE-HBR scores show moderate discrimination (c-statistic 0.64-0.75). Contemporary data therefore support replacing one-size-fits-all 12-month DAPT with risk-guided algorithms for post-PCI antithrombotic therapy.
Thierry Kochkarian, Anis Ismail, Omar Chaabo et al.· Catheterization and cardiova...· 0 citations
Abstract Current evidence indicates that antiplatelet therapy as a cornerstone for secondary prevention of cerebral infarction. However, ischemic or bleeding events arising from antiplatelet drug resistance or excessive platelet inhibition can diminish its clinical benefit. These challenges have laid the foundation for individualized antiplatelet treatment. Although cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genetic polymorphisms have partially addressed the issue of drug resistance in these patients, they remain insufficient to resolve the high incidence of both ischemic and bleeding events. Platelet function testing (PFT)‐guided antiplatelet therapy has been proven beneficial in patients after percutaneous coronary intervention, yet its efficacy in patients with cerebral infarction remains controversial. Platelet function provides a direct and comprehensive reflection of antiplatelet effects, offering potential not only to overcome drug resistance but also to guide de‐escalation strategies, thereby mitigating the frequent occurrence of both ischemic and bleeding events in cerebral infarction. Overall, the current application of PFT to guide personalized antiplatelet regimens in patients with cerebral infarction is characterized by considerable variability. In light of recent advances in this field, we herein review the current landscape of PFT‐guided individualized antiplatelet therapy in cerebral infarction, with the aim of summarizing existing evidence and offering suggestions for future research.
Background Heart failure with reduced ejection fraction (HFrEF) remains a major cause of morbidity, mortality, and healthcare utilization worldwide despite substantial therapeutic advances. Over the past three decades, randomized clinical trials have established four foundational pharmacologic pillars of guideline-directed medical therapy (GDMT): renin—angiotensin system inhibition or angiotensin receptor—neprilysin inhibition, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium—glucose cotransporter 2 inhibitors. However, real-world implementation of these therapies remains suboptimal. Objectives To provide a contemporary state-of-the-art review of current evidence supporting GDMT in HFrEF, examine unresolved challenges in sequencing and optimization, and propose a practical phenotype-based framework to support individualized treatment decisions. Methods A structured narrative review was conducted using PubMed/MEDLINE, Embase, and Google Scholar to identify relevant publications from January 2000 to February 2026. Priority was given to randomized controlled trials, international guidelines, meta-analyses, and high-quality observational registries addressing GDMT initiation, sequencing, tolerability, and implementation. Results Robust evidence supports early and combined use of the four foundational GDMT classes, with substantial reductions in mortality and heart failure hospitalization. Emerging data favor rapid initiation of multiple therapies followed by structured uptitration rather than prolonged sequential strategies. Nevertheless, important barriers persist, including hypotension, renal dysfunction, hyperkalemia, frailty, polypharmacy, therapeutic inertia, and inequitable access to medications. Current guidelines provide limited practical direction regarding treatment prioritization in complex clinical phenotypes. A phenotype-based decision framework may facilitate earlier, safer, and more individualized implementation of GDMT in routine practice. Conclusions The principal challenge in modern HFrEF management is no longer the absence of effective therapies, but failure to deliver proven therapies rapidly, comprehensively, and sustainably. Future progress may depend less on development of new drug classes and more on optimizing implementation of currently available life-saving treatments through phenotype-informed and patient-centered strategies.
Ehsan Shahverdi, Amin Shahverdi, Sendooran Shahi et al.· Journal of the Saudi Heart A...· 0 citations
PURPOSE
Clopidogrel is a cornerstone of antiplatelet therapy after lower-limb endovascular intervention in patients with peripheral arterial disease (PAD), yet interindividual variability in treatment response may influence clinical outcomes. To our knowledge, this is the first systematic review and meta-analysis to combine an updated quantitative synthesis of functional clopidogrel resistance with a dedicated qualitative appraisal of CYP2C19 genetic determinants, while explicitly separating analyses based on raw event data from exploratory analyses using published effect estimates and applying conservative small-sample sensitivity methods. We evaluated the association between functional clopidogrel resistance and clinically relevant limb outcomes-target lesion/target vessel revascularization (TLR/TVR) and major adverse limb events (MALE)-with all-cause mortality as a secondary exploratory outcome.
METHODS
The review was conducted according to PRISMA 2020 and registered in PROSPERO (CRD42026129845). MEDLINE (PubMed), EMBASE, Web of Science, and Google Scholar were searched from inception to May 17, 2026. Functional resistance was defined as high on-treatment platelet reactivity (HTPR) assessed by platelet function testing, and genetic determinants as CYP2C19 loss-of-function alleles or metabolizer status associated with impaired clopidogrel response. Random-effects meta-analyses using restricted maximum likelihood (REML) were performed, with Hartung-Knapp-Sidik-Jonkman (HKSJ) sensitivity analyses and prediction intervals to quantify statistical uncertainty in sparse data. Genetic studies were synthesized qualitatively.
FINDINGS
Ten studies met the inclusion criteria; 6 functional studies contributed to the quantitative analyses. In the primary analysis based on 3 studies with raw event data, HTPR was associated with an approximately 3.7-fold increase in TLR/TVR risk (odd ratios [OR] 3.68; 95% confidence interval [CI] 1.56-8.68; P = 0.003; I² = 59%). An exploratory analysis of 5 studies with published effect estimates was directionally consistent (OR 4.46; 95% CI 1.09-18.31; I² = 87%). HKSJ sensitivity analyses preserved the direction of effect but produced substantially wider confidence intervals crossing the null, indicating increased statistical uncertainty. HTPR was not significantly associated with all-cause mortality (OR 1.49; 95% CI 0.92-2.42).
IMPLICATIONS
Functional clopidogrel resistance may be associated with an approximately 3- to 4-fold higher risk of repeat revascularization after lower-limb endovascular intervention; however, the small number of studies, substantial heterogeneity, and conservative sensitivity analyses warrant cautious interpretation. Larger prospective studies and randomized trials are needed before platelet-function-guided or genotype-guided antiplatelet strategies can be recommended.
PROSPERO REGISTRATION
CRD42026129845.
M. L. Del Rio-Sola, Sandra Pérez-Fernández, Marina Jiménez-Caja et al.· Clinical Therapeutics· 0 citations
The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceride-rich lipoproteins, lipoprotein(a), and vascular inflammation. The emergence of PCSK9-targeted small interfering RNA therapies, CETP inhibitors, and Lp(a)-directed antisense and RNA based agents has enabled complementary modulation of diverse lipid pathways through distinct molecular targets. However, this increasingly multidrug approach may also increase treatment complexity, healthcare burden, and adherence challenges, particularly among high-risk patients already receiving multidrug cardiometabolic therapy. Although intensive and sustained LDL-C lowering remains foundational to preventive cardiology, the real-world effectiveness of increasingly complex treatment strategies may ultimately depend on long-term adherence, affordability, patient capacity, and implementation feasibility. We propose a Clinical Prioritization and Personalization Framework centered on individualized risk-based intensification, comprehensive residual risk management, and optimization of treatment delivery to achieve sustainable, patient-centered cardiovascular protection.
Yashendra Sethi, K. Mahajan, Michael D. Shapiro et al.· Progress in cardiovascular d...· 1 citation