Clopidogrel resistance and its relevance: Current concepts.

Clopidogrel is the most widely used P2Y12 receptor inhibitor (P2Y12i) as a part of dual antiplatelet therapy along with aspirin. Clopidogrel is a pro-drug and is metabolized to its active metabolite by the hepatic enzyme cytochrome P4502C19 (CYP2C19). This active metabolite is responsible for the antiplatelet action of clopidogrel. Recent studies have demonstrated that single nucleotide polymorphisms in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5 alleles, result in reduced production of the active metabolite of clopidogrel, and hence reduced inhibition of platelet aggregation. This in turn enhances the incidence of stent thrombosis and recurrent cardiovascular (CV) events. We report a case of coronary stent thrombosis due to clopidogrel resistance proven by CYP2C19 genotyping. We then review the literature on clopidogrel resistance and its impact on CV outcomes. Subsequently, we discuss the methods of diagnosis of resistance, evidence from clinical trials for tailoring clopidogrel therapy, the role of potent P2Y12 inhibitors, the current guidelines, and future directions.

Role of Cyp2c19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: Identification of a reliable discriminatory test to accurately stratify patient responses to antiplatelet therapy following coronary revascularization has become increasingly desirable to optimize therapeutic efficacy and safety. RECENT FINDINGS: The expansion of platelet function testing to include genotype assessment has been an evolutionary journey, initially fraught with confounding results. However, more recent and rigorous data analysis suggests that genotype testing- guided, tailored antiplatelet therapy may hold promise in optimizing treatment of patients after coronary intervention. Current evidence increasingly supports the use of genotype guided CYP2C19 testing to better match the post coronary intervention patient with the most efficacious and least risky antiplatelet inhibitor. The risk stratification of poor, intermediate, and good metabolizers of these drugs with such testing promises to yield clinical dividends in terms of morbidity, mortality and cost control, in this growing patient population.

Current Strategies to Guide the Antiplatelet Therapy in Acute Coronary Syndromes.

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.

Platelet function testing: Update on determinant variables and permissive windows using a platelet-count-based device.

While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet function is that which gives a measure of the platelet aggregation capacity upon stimulation with an agonist. Platelet function testing is necessary for the diagnosis of platelet disorders and the monitoring of patients receiving anti-platelet treatments. Furthermore, it becomes relevant in the quality control of platelet concentrates for transfusion purposes, especially considering the global concern about long term storage, other forms of storage (i.e. cryopreservation, lyophilization), and the impact of Pathogen Reduction Treatments (PRTs) on platelet performance upon transfusion. However, it has been acknowledged as technically difficult and demanding, since a fine platelet function test must be carried out under specific conditions. Still, there might be occasions that preclude the platelet function testing abiding to the gold standard requirements, thus, leaving us with the necessity to redefine which variables may condition or limit the analysis of platelet function testing. In the present manuscript, we test different variables (such as the anticoagulant used or the time elapsed since extraction) and the possibility to reconstitute blood prior to platelet function analysis. This study aims to provide windows of action at the diagnostics lab, especially when not all of the recommended procedures and conditions can be followed: for example, when a sample is sent from a long distance, when there is a limitation on blood extraction volume or when certain parameters (platelet count) preclude reliable test results.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

Advances and Perspectives in methods for identifying high platelet reactivity.

Antiplatelet therapy is the foundational treatment for the prevention and treatment of coronary and cerebrovascular ischemic events in patients with coronary heart disease, ischemic stroke, and transient ischemic attack (TIA). However, with more and more studies reporting an increased risk of thrombosis in some patients due to poor response to therapeutic agents, the selection of appropriate P2Y12 inhibitors has become a major challenge that needs to be addressed urgently. Currently, commonly used oral P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel. Assessing patients' risk factors before the development of treatment regimens by effectively predicting the risk of high platelet reactivity with specific P2Y12 inhibitors in advance to avert the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) is the key point to the problem. Up to now, methods available for predicting platelet reactivity include genetic testing, platelet function testing, and risk scores. This review provides a summarization of the existent available identification methods and analyzes the advantages and drawbacks of different methods in specific clinical settings, intending to guide the rational clinical application of P2Y12 receptor inhibitors.

Clinical Assessment of Primary Hemostasis: A Review.

Primary hemostatic disorders such as thrombocytopenia and thrombocytopathia are commonly encountered in small animal practice. The key stages of primary hemostasis include platelet adhesion, activation, and aggregation. Understanding the interaction between tissues, platelets, and signaling molecules not only helps clinicians comprehend clot formation but also better recognize thrombocytopathias. Although congenital thrombocytopathia is rare, commercially available platelet function tests allow veterinarians to narrow differentials in many clinical settings. Thrombocytopenia can be easily diagnosed in any clinical setting. In this paper, we review the current understanding of primary hemostasis in veterinary medicine, including the clinical presentation and available diagnostics to identify platelet abnormalities.

Personalised antiplatelet therapies for coronary artery disease: what the future holds.

Coronary artery disease (CAD) is one of the leading causes of death globally, and antiplatelet therapy is crucial for both its prevention and treatment. Antiplatelet drugs such as aspirin and P2Y12 inhibitors are commonly used to reduce the risk of thrombotic events, including myocardial infarction, stroke, and stent thrombosis. However, the benefits associated with the use of antiplatelet drugs also come with a risk of bleeding complications. The ever-growing understanding of the poor prognostic implications associated with bleeding has set the foundations for defining strategies that can mitigate such safety concern without any trade-off in antithrombotic protection. To this extent, personalised antiplatelet therapy has emerged as a paradigm that optimizes the balance between safety and efficacy by customizing treatment to the individual patient's needs and risk profile. Accurate risk stratification for both bleeding and thrombosis can aid in selecting the optimal antiplatelet therapy and prevent serious and life-threatening outcomes. Risk stratification has traditionally included clinical and demographic characteristics and has expanded to incorporate angiographic features and laboratory findings. The availability of bedside platelet function testing as well as rapid genotyping assays has also allowed for a more individualized selection of antiplatelet therapy. This review provides a comprehensive overview of the current state of the art and future trends in personalised antiplatelet therapy for patients with CAD, with emphasis on those presenting with an acute coronary syndrome and undergoing percutaneous coronary revascularization. The aim is to provide clinicians with a comprehensive understanding of personalised antiplatelet therapy and facilitate informed clinical decision-making.

Individualized or Uniform De-Escalation Strategies for Antiplatelet Therapy in Acute Coronary Syndrome: A Review of Clinical Trials with Platelet Function Testing and Genetic Testing-Based Protocols.

This comprehensive literature review assessed the effectiveness of precision medicine approaches in individualizing P2Y12 de-escalation strategies, such as platelet function testing guidance, genetic testing guidance, and uniform de-escalation, for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Analyzing six trials with a total of 13,729 patients, the cumulative analyses demonstrated a significant reduction in major adverse cardiac events (MACE), net adverse clinical events (NACE), and major and minor bleeding events with P2Y12 de-escalation. Specifically, the analysis found a 24% reduction of MACE and a 22% reduction of adverse event risk (relative risk (RR) 0.76, 95% confidence interval (CI): 0.71-0.82, and RR: 0.78, 95% CI 0.67-0.92, respectively). Reductions in bleeding events were highest with uniform unguided de-escalation, followed by guided de-escalations, while ischemic event rates were similarly lower across all three strategies. Although the review highlights the potential of individualized P2Y12 de-escalation strategies to offer a safer alternative to the long-term potent P2Y12 inhibitor-based dual antiplatelet therapy, it also indicates that laboratory-guided precision medicine approaches may not yet offer the expected benefits, necessitating further research to optimize individualized strategies and evaluate the potential of precision medicine approaches in this context.

Guided vs. conventional anti-platelet therapy for patients with acute coronary syndrome: A meta-analysis of randomized controlled trials.

Background: Whether guided antiplatelet therapy in patients with acute coronary syndrome (ACS) is effective in improving net clinical benefits compared with conventional antiplatelet therapy remains controversial. Therefore, we assessed the safety and efficacy of guided antiplatelet therapy in patients with ACS and undergoing percutaneous coronary intervention. Method: We searched PubMed, EMBASE, and Cochrane Library databases to select the relevant randomized controlled trials comparing the guided and conventional antiplatelet therapy in patients with ACS. The primary and safety outcomes are major adverse cardiovascular events (MACE) and major bleeding, respectively. The efficacy outcomes included myocardial infarction, stent thrombosis, all-cause death, and cardiovascular death. We selected the relative risk (RR) and 95% confidence intervals (CIs) as effect size and calculated it using the Review Manager software. In addition, we evaluated the final results by trial sequential analysis (registered by PROSPERO, CRD 42020210912). Results: We selected seven randomized controlled trials and included 8,451 patients in this meta-analysis. Guided antiplatelet therapy can significantly reduce the risk of MACE (RR 0.64, 95% CI 0.54-0.76, P < 0.00001), myocardial infarction (RR 0.62, 95% CI 0.49-0.79, P = 0.0001), all-cause death (RR 0.61, 95% CI 0.44-0.85, P = 0.003), and cardiovascular death (RR 0.66, 0.49-0.90, P = 0.009). In addition, there is no significant difference between the two groups in stent thrombosis (RR 0.67, 95% CI 0.44-1.03, P = 0.07) and major bleeding (RR 0.86, 95% CI 0.65-1.13, P = 0.27). The subgroup analysis showed that the guided group based on genotype tests could bring benefits in MACE and myocardial infarction. Conclusions: The guided antiplatelet therapy is not only associated with a comparable risk of bleeding but also with a lower risk of MACE, myocardial infarction, all-cause death, cardiovascular death, and stent thrombosis than the conventional strategy in patients with ACS.

Impact of body mass on P2Y12-inhibitor de-escalation in acute coronary syndromes-a substudy of the TROPICAL-ACS trial.

AIMS: Clinical guidelines recommend de-escalation antiplatelet strategies to reduce bleeding risk in acute coronary syndrome (ACS) patients, albeit with a weak recommendation. This substudy of the TROPICAL-ACS trial aimed to determine the impact of body mass on the efficacy of a platelet function testing-guided de-escalation regimen in ACS patients after percutaneous coronary intervention. METHODS AND RESULTS: Patients were randomized to prasugrel (control group) or a platelet function testing-guided regimen with clopidogrel or prasugrel defined after 1-week clopidogrel. The primary endpoint was the net clinical benefit [cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) 2-5 bleeding] for 12 months. Overweight was defined as a body mass index >25 kg/m2.Patients without overweight showed a significant net clinical benefit from the de-escalation strategy, while in overweight cases de-escalation was comparable to prasugrel treatment [hazard ratio (HR): 0.52; 95% confidence interval (CI): 0.31-0.88; P = 0.013 and HR: 0.95; 95% CI: 0.69-1.31, P = 0.717, P-non-inferiority = 0.03, respectively, P-interaction = 0.053]. The benefit of de-escalation in terms of the risk of bleeding or of the ischaemic events did not reach statistical significance. Bleeding events with de-escalation were less frequent in non-overweight patients but comparable in overweight patients (HR: 0.55; 95% CI: 0.30-1.03; P = 0.057 and HR: 0.95; 95% CI: 0.64-1.41, respectively, P-interaction = 0.147). Non-overweight patients had lower ischaemic event rates with de-escalation, while overweight cases had slightly less (HR: 0.47; 95% CI: 0.18-1.25; P = 0.128 and HR: 0.89; 95% CI: 0.53-1.50, respectively, P-interaction = 0.261). CONCLUSION: The strategy of guided dual antiplatelet therapy de-escalation was associated with a significant net clinical benefit in non-overweight patients, while the two strategies were equivalent in overweight patients.

Role of platelet function and genetic testing in patients undergoing percutaneous coronary intervention.

Dual antiplatelet therapy (DAPT) represents the standard of care for patients undergoing percutaneous coronary intervention (PCI). Increasing evidence indicates that a "one-size-fits-all" approach with the use of a standard DAPT regimen for all patients undergoing PCI could lead to either suboptimal efficacy or prohibitively high bleeding in specific cohorts of patients. Moreover, the broad interindividual variability in response to P2Y12 inhibitors can impact outcomes and resource utilization. Among the strategies proposed to provide a more balanced trade-off between bleeding and ischemic events at a single patient level, a guided selection of P2Y12 inhibitors, by using platelet function or genetic testing, has shown promising results. In this review, we provide a focused summary of the rationale and evidence on the use of platelet function and genetic testing-guided antiplatelet therapy, and we explore the implications for their use in the modern setting of patients undergoing PCI.

Implementation of the new EUR IVD regulation and relation with ISO15189 accreditation: Guidance is urgently required for haemostasis testing.

On May 26th 2017 the European Parliament and the Council of The European Union adopted the new regulation on in vitro diagnostic medical devices (IVDR)-Regulation EU 2017/746-planned to be applied from May 26th 2022 in substitution to the previous IVD directives (IVDD 98/79 EC). After several health and legal causes due to medical device malfunctions, the European Union (EU) extensively reviewed the previous regulatory, which had remained unchanged since 1998. Aim of the work is to analyse the effects of the new IVDR on the field of haemostasis and thrombosis testing with particular attention to specific clinical conditions. Clinical laboratories will mainly deal with three different situations: (1) Diagnostic test performed with IVDR products used according with clinical indication certified by manufacturers. (2) Diagnostic test performed with certified IVDR products without clinical validation. (3) Diagnostic test performed with reagents classified as Research Use Only (RUO). At present, only few clinical laboratories through different European countries have been prepared to the new IVDR, while many laboratories are not yet aware about crucial aspects of the new process that deeply involves laboratory medicine. In conclusion, each laboratory should be aware of the IVDR certification of the reagents/instruments used in its laboratory. There are several urgent needs regarding IVDR certification: studies about the clinical performance of haemostasis tests, guidelines for LDTs (definition and documentation), internal and external quality controls for the tests recommended/suggested in the guidance/guidelines and finally implementation and/or update of clinical and laboratory guidelines.

Platelet reactivity after clopidogrel loading in patients with acute ischemic stroke.

Objective: It remains unclear when sufficient antiplatelet effect is achieved after administration of a loading dose of clopidogrel in patients with acute ischemic stroke (AIS). This study aimed to evaluate the clopidogrel response in patients with AIS identified by the platelet function test (PFT). Methods: P2Y12 reaction unit (PRU) values measured using VerifyNow at baseline and at 6, 24, and 72 h after administration of a loading dose (300 mg) of clopidogrel were compared between patients with AIS and those of other cerebrovascular diseases (CVD). The prevalence of clopidogrel abnormal response and its associated factors were examined. Results: The PRU value was significantly reduced with time in the other CVD group (p < 0.0001), and also in the AIS group (p = 0.0073). The PRU values were significantly higher in the AIS group than in the other CVD group (p < 0.0001 between the groups, baseline: 314 ± 53 vs. 284 ± 62, p = 0.35; 6 h: 290 ± 66 vs. 214 ± 71, p = 0.016; 24 h: 270 ± 75 vs. 190 ± 70, p < 0.0001; and 72 h: 231 ± 76 vs. 163 ± 93, p = 0.105). The prevalence of clopidogrel hypo-responder (PRU > 240 at 24 h after administration) was higher in the AIS group (79 vs. 33%, p < 0.0001) and associated with the baseline PRU value but not with the cytochrome P450 2C19 genotype or clinical ischemic events. Conclusions: Residual platelet reactivity at 24 h after clopidogrel loading was substantially higher in patients with AIS than in patients with other CVD. In addition, most patients with AIS were judged to be hypo-responders on PFT. This should be carefully interpreted in patients with AIS because of poor specificity for predicting clinical ischemic events.

Precision medicine in interventional cardiology: implications for antiplatelet therapy in patients undergoing percutaneous coronary intervention.

Precision medicine is a medical model that proposes the customization of medical treatments to the individual patient, as opposed to a one-drug-fits-all model. Such a "personalized medicine" approach has been widely adopted in several medical fields, such as cancer medicine, but the implementation of precision medicine in cardiovascular medicine has not been similarly straightforward. Because pharmacogenomics plays an important role in the safety and efficacy of cardiovascular drug therapy, there has been a great interest in the use of tools aiming at personalizing antiplatelet therapy. Moreover, antiplatelet therapy is essential for the treatment of cardiovascular patients to reduce the risk of thrombotic complications, particularly those undergoing percutaneous coronary intervention, but it is inevitably associated with increased bleeding risk. In this review, the authors discuss the rationale, summarize the evidence and discuss the current and future directions for the personalization of antiplatelet treatment regimens in patients undergoing percutaneous coronary intervention.

A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia.

Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k2)=0.84], supporting its role as a useful screening tool in the assessment of platelet function. Optimul assay performance was quick and the methodology simple, requiring no specialised training or resources to be implemented at either the regional or metropolitan laboratory. Widespread implementation, particularly in regional laboratories within Australia where specialised platelet function testing is unavailable, has the potential to drastically improve the inequity of access to such services.

Platelet function testing: Current practice among clinical centres in Northern Europe.

INTRODUCTION: Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing. AIMS: To identify current practice among centres performing platelet function tests in Northern Europe. METHODS: A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million. RESULTS: Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres. CONCLUSIONS: The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Long-term effects of baseline on-treatment platelet reactivity in patients with acute coronary syndrome and thrombocytopenia undergoing percutaneous coronary intervention.

OBJECTIVE: To analyse the association between on-treatment platelet reactivity (TPR) and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. METHODS: This prospective observational study enrolled patients with coronary artery disease (CAD) that underwent percutaneous coronary intervention (PCI). Patients with ACS and TP under dual antiplatelet therapy were selected for analysis. The 2- and 5-year clinical outcomes were evaluated among patients with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), as tested by thromboelastogram at baseline. RESULTS: A total of 10 724 patients with CAD that underwent PCI were identified. Of these, 474 patients with ACS and TP met the inclusion criteria: 124 (26.2%) with HTPR, 163 (34.4%) with LTPR and 187 (39.5%) with NTPR. The 5-year rates of all-cause death, major adverse cardiovascular and cerebrovascular events, cardiac death, myocardial infarction, revascularization, stroke and bleeding were not significantly different among the three groups. Multivariate Cox regression analysis demonstrated that patients with HTPR were not independently associated with any of the 5-year endpoints compared with patients with NTPR. CONCLUSIONS: TPR at baseline was not independently associated with long-term outcomes in patients with ACS and TP that underwent PCI.

Safety considerations with the use of platelet inhibitors for elderly patients with non-ST- elevation acute coronary syndrome.

Introduction: Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndrome (ACS). This includes lifelong aspirin combined with a P2Y12 inhibitor for 1 year. The indication for one of the P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) is dependent on the treatment strategy; whether patients undergo coronary angiography or are treated medically only. Tailoring antiplatelet therapy to the risk profile of the individual patient is of specific importance to the older patient.Areas covered: In this review, we discuss dual antiplatelet therapy in elderly patients with ACS. We present the options to tailor antiplatelet therapy based on platelet function testing, CYP2C19 genotyping and patients' thrombotic and bleeding risk. Finally, we discuss alternatives for dual antiplatelet therapy.Expert opinion: DAPT in elderly patients with ACS should consist of aspirin with clopidogrel or ticagrelor. Weighing patients' thrombotic and bleeding risk, based on clinical judgment or with use of specific risk scores, is probably the most convenient method to individualize antiplatelet therapy; however, CYP2C19 genotyping can also be used. In elderly patients with an increased bleeding risk, clopidogrel is a safe and effective alternative to ticagrelor. An alternative to 12 months DAPT could be ticagrelor monotherapy after a short period of DAPT.