Selecting optimal antiplatelet therapy based on platelet function monitoring in patients with coronary artery disease

Opinion statement  Results from pharmacodynamic and translational research studies assessing platelet reactivity have highlighted the limitations of current oral antiplatelet therapy. The data from translational research studies present strong arguments against the “one-size-fits-all” approach that has been used in large-scale clinical trials. At one end of the spectrum, selected patients with excessively low on-treatment platelet reactivity may have unnecessary bleeding, whereas patients with high platelet reactivity may experience ischemic events. Current evidence suggests that high on-treatment platelet reactivity will become a major risk factor determined as standard of care in patients with cardiovascular diseases. Future translational research holds the promise of identifying a therapeutic window for antiplatelet therapy based on objective measurement of platelet physiology. The main aim of this therapeutic window is to effectively attenuate ischemic events while avoiding bleeding risk with excessive platelet inhibition in selected patients with optimal antiplatelet therapeutic strategies involving current or novel antiplatelet agents. Preliminary findings suggest there may be thresholds predictive of adverse ischemic events. Ongoing studies such as GRAVITAS (Gauging Responsiveness With a Verify Now Assay—Impact on Thrombosis and Safety) and the S.T.E.N.T. Thrombosis Study and future research will likely support the current concepts and lead to personalized treatment regimens that will optimize antiplatelet therapy.     

Oral antiplatelet therapy for atherothrombotic disease: current evidence and new directions

Despite the proven efficacy of dual antiplatelet therapy with aspirin and one of the first-generation P2Y(12) antagonists (clopidogrel, prasugrel) in patients with atherothrombotic disease, residual ischemic risk remains substantial, and bleeding rates are increased. Incomplete protection against ischemic events can be attributed to the fact that these therapies each target a single platelet activation pathway, allowing continued platelet activation via other pathways, including the protease-activated receptor-1 (PAR-1) pathway stimulated by thrombin. Increased bleeding with dual antiplatelet therapy can be attributed to blockade of the thromboxane A(2) (by aspirin) and adenosine diphosphate (by P2Y(12) antagonist) platelet activation pathways that are essential to hemostasis. The second-generation P2Y(12) inhibitor ticagrelor plus aspirin demonstrated superior ischemic outcomes, including reduction in total mortality, versus clopidogrel plus aspirin, but event rates remain high, and major bleeding not related to coronary artery bypass grafting is increased. The novel P2Y(12) antagonist elinogrel, available in intravenous and oral formulations, may have a more favorable benefit-to-risk profile than existing agents in this class because of reversible and competitive binding to the P2Y(12) receptor. Inhibition of PAR-1 is an attractive, novel approach in antiplatelet therapy because it may provide incremental ischemic protection without increasing bleeding. The PAR-1 antagonist vorapaxar (SCH 530348) has been associated with favorable efficacy and safety in phase 2 trials. Two phase 3 trials are evaluating the efficacy and safety of vorapaxar in patients presenting with non-ST-segment elevation acute coronary syndromes and in patients with documented atherothrombotic disease.     

Personalizing antiplatelet therapies: What have we learned from recent trials?

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is currently the standard of care for the prevention of ischemic events in patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Several studies have shown that not all patients benefit from the treatment to the same degree and demonstrated that high on-treatment platelet reactivity may be associated with an increased risk of thrombotic events, while low on-treatment platelet reactivity may be linked to a higher risk of bleeding. Personalized antiplatelet treatment strategies based on platelet function monitoring and genetic testing constitute a promising tool for the prevention of both stent thrombosis and bleeding events, but conclusive evidence that such approaches can improve clinical outcomes is lacking. This review presents the most recent studies on tailored antiplatelet therapy in the management of coronary heart disease, with a focus on the prognosis value of platelet function testing.     

Effects of antiplatelet therapy on platelet extracellular vesicle release and procoagulant activity in health and in cardiovascular disease

Dual antiplatelet therapy with aspirin and clopidogrel is commonly used to prevent recurrent ischemic events in patients with cardiovascular disease. Whilst their effects on platelet reactivity are well documented, it is unclear, however, whether antiplatelet therapy inhibits platelet extracellular vesicle (EV) release. The aim of this study was to investigate the effects of antiplatelet therapy on platelet EV formation and procoagulant activity.

Blood samples from 10 healthy controls not receiving antiplatelet therapy were incubated in vitro with aspirin or a P2Y12 inhibitor (MeSAMP). Blood samples from 50 patients receiving long-term dual antiplatelet therapy and undergoing coronary angiography were also studied. Platelet reactivity was assessed by Multiplate? impedance aggregometry. Platelet EV formation and procoagulant activity of pretreated and untreated blood samples in response to arachidonic acid (AA), adenosine diphosphate (ADP), ADP+PGE1, and thrombin receptor-activating peptide (TRAP) stimulation were assessed by flow cytometry and Procoag-PL assays, respectively.

Incubation of normal platelets with aspirin significantly inhibited AA-induced platelet reactivity, EV formation, and procoagulant activity, whilst MeSAMP significantly inhibited platelet reactivity and EV formation in response to AA, ADP, and TRAP, but had minimal effect on procoagulant activity. Most patients receiving dual antiplatelet therapy showed an appropriate reduction in platelet reactivity in response to their treatment; however there was not complete inhibition of increased platelet and EV procoagulant activity in response to ADP, AA, or TRAP. In addition, we could not find any correlation between platelet reactivity and procoagulant activity in patients receiving dual antiplatelet therapy.     

Tratamiento antiagregante plaquetario personalizado

It is well established that high on-treatment platelet reactivity to adenosine diphosphate during clopidogrel therapy is an independent risk factor for ischemic event occurrences in a postpercutaneous coronary intervention patients. However, the precise role of platelet function testing remains debated. Platelet function testing to ensure optimal platelet inhibition has been recommended by some authorities to improve outcomes in patients treated with clopidogrel. Recent prospective, randomized trials of personalized antiplatelet therapy have failed to demonstrate a benefit of platelet function testing in improving outcomes. In this review article, we discuss the mechanisms responsible for clopidogrel nonreponsiveness, recent trials of platelet function testing, and other new developments in the field of personalized antiplatelet therapy.     

The use of the VerifyNow system to monitor antiplatelet therapy: a review of the current evidence

Multiple studies have demonstrated the effectiveness of dual or triple antiplatelet therapy with aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa therapy in patients with acute coronary syndromes as well as in patients undergoing coronary stent implantation. In the last few years, it is becoming clear that not all patients receive the full benefits with the current standard dosages of antiplatelet therapy. Specifically, numerous studies have revealed a wide interindividual variability in the response to these antiplatelet agents and, more importantly, both nonresponsiveness as well as a heightened residual platelet reactivity have been linked to the occurrence of adverse cardiovascular events. Therefore, assays that identify those patients with an impaired responsiveness or a heightened platelet reactivity despite dual antiplatelet therapy may contribute to better risk stratification and will probably improve clinical outcome when appropriate action is initiated. Likewise, a considerable number of patients do not achieve the minimal inhibition of aggregation threshold with the current recommended weight-adjusted dosages of GP IIb/IIIa therapy. Identifying and optimizing the absolute degree of platelet inhibition in this subgroup of patients will probably improve clinical outcome. The VerifyNow platform is one of the most user friendly point-of-care platelet function test systems because it produces rapid results at the patient bedside. The purpose of the present paper is to give insight into the principal mechanisms of the VerifyNow system, to discuss its clinical utility for the monitoring of antiplatelet therapy and to discuss the proposed cut-off levels to segregate responders from non-responders for the different types of antiplatelet therapy.     

The use of the VerifyNow system to monitor antiplatelet therapy: A review of the current evidence

Multiple studies have demonstrated the effectiveness of dual or triple antiplatelet therapy with aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa therapy in patients with acute coronary syndromes as well as in patients undergoing coronary stent implantation. In the last few years, it is becoming clear that not all patients receive the full benefits with the current standard dosages of antiplatelet therapy. Specifically, numerous studies have revealed a wide interindividual variability in the response to these antiplatelet agents and, more importantly, both nonresponsiveness as well as a heightened residual platelet reactivity have been linked to the occurrence of adverse cardiovascular events. Therefore, assays that identify those patients with an impaired responsiveness or a heightened platelet reactivity despite dual antiplatelet therapy may contribute to better risk stratification and will probably improve clinical outcome when appropriate action is initiated. Likewise, a considerable number of patients do not achieve the minimal inhibition of aggregation threshold with the current recommended weight-adjusted dosages of GP IIb/IIIa therapy. Identifying and optimizing the absolute degree of platelet inhibition in this subgroup of patients will probably improve clinical outcome. The VerifyNow platform is one of the most user friendly point-of-care platelet function test systems because it produces rapid results at the patient bedside. The purpose of the present paper is to give insight into the principal mechanisms of the VerifyNow system, to discuss its clinical utility for the monitoring of antiplatelet therapy and to discuss the proposed cut-off levels to segregate responders from non-responders for the different types of antiplatelet therapy.     

血小板功能检测与P2Y12受体拮抗剂个体化抗血小板治疗的研究进展

P2Y12受体拮抗剂广泛应用于急性冠脉综合征（ACS）及经皮冠状动脉介入治疗（PCI）后血栓事件的预防。由于抗血小板治疗反应多样性的存在,经典的P2Y12受体拮抗剂氯吡格雷的治疗期间高血小板反应性（HTPR）被证实与患者不良心血管事件的发生密切相关。尽管新药普拉格雷和替格瑞洛的抗栓疗效优于氯吡格雷,但是由于治疗期间低血小板反应性（LTPR）的存在,出血风险明显增加。如何权衡血栓和出血风险,实现个体化抗血小板治疗,已经成为临床的重要挑战。研究证实,血小板反应性（PR）与缺血和出血事件的发生密切有关,基于血小板功能检测（PFT）的治疗窗将有助于个体化抗血小板治疗。本文就PFT与P2Y12受体拮抗剂个体化抗血小板治疗的研究进展作一综述。     

P2Y12-ADP receptor antagonists: Days of future and past

Antiplatelet therapy is the cornerstone of the therapeutic arsenal in coronary artery disease.Thanks to a better understanding in physiology,pharmacology and pharmacogenomics huge progress were made in the field of platelet reactivity inhibition thus allowing theexpansion of percutaneous coronary intervention.Stent implantation requires the combination of two antiplatelet agents acting in a synergistic way.Asprin inhibit the cyclo-oxygenase pathway of platelet activation while clopidogrel is a P2Y12 adenosine diphosphate(ADP)-receptor antagonist.This dual antiplatelet therapy has dramatically improved the prognosis of stented patients.However,due to pharmacological limitations of clopidogrel(interindividual variability in its biological efficacy,slow onset of action,mild platelet reactivity inhibition)ischemic recurrences remained high following stent implantation especially in acute coronary syndrome patients.Thus,more potent P2Y12-ADP receptor inhibitors were developped including prasugrel,ticagrelor and more recently cangrelor to overcome these pitfalls.These new agents reduced the rate of thrombotic events in acute coronary syndrome patients at the cost of an increased bleeding risk.The abundance in antiplatelet agents allow us to tailor our strategy based on the thrombotic/bleeding profile of each patient.Recently,the ACCOAST trial cast a doubt on the benefit of pre treatment in non-ST segment elevation acute coronary syndrome.The aim of the present review is to summarize the results of the main studies dealing with antiplatelet therapy in stented/acute coronary syndromes patients.     

The “Dual‐Pathway” Strategy after Acute Coronary Syndrome: Rivaroxaban and Antiplatelet Agents in the ATLAS ACS 2‐TIMI 51 Trial

Acute coronary syndrome (ACS) is a medical emergency often associated with an occlusive coronary event with consequent myocardial underperfusion. Patients require immediate antiplatelet therapy and long‐term antithrombotic prophylaxis to reduce the risk of recurrence. Acetylsalicylic acid (ASA) alone or in combination with a platelet P2Y₁₂ inhibitor (dual antiplatelet therapy [DAPT]) has become the clinically accepted antithrombotic prophylaxis for patients post‐ACS. Historically, studies assessing the utility of adding oral anticoagulants (OACs) have not demonstrated a clinical benefit with regard to acceptable bleeding risk. Studies with vitamin K antagonists (VKAs) such as warfarin demonstrated a potential to reduce the risk of subsequent death by reinfarction but this benefit was offset by increases in bleeding. Results from studies of two targeted non‐VKA OACs also proved disappointing, with little or no apparent reduction in the rate of ischemic events seen. However, the recent ATLAS studies assessing rivaroxaban (an oral factor Xa inhibitor) in patients with ACS demonstrated a reduction in the composite endpoint of deaths from cardiovascular causes, myocardial infarction (MI), or stroke, and a reduction in the rate of stent thrombosis. This review provides an overview of the pivotal studies in which the addition of OACs to antiplatelet therapy (the so‐called “dual‐pathway” approach) has been investigated for the management of patients post‐ACS and considers the results of the ATLAS studies and their potential impact on the management of patients after an acute event.     

Coronary Calcium: New Insights, Recent Data, and Clinical Role

Antiplatelet therapy with aspirin and a platelet P2Y12 receptor antagonist reduces thrombotic and ischemic events after percutaneous coronary intervention and acute coronary syndrome. The platelet inhibitory effect of the thienopyridine clopidogrel varies widely among individuals, and high on-treatment platelet reactivity has been associated with a substantial hazard for post-PCI cardiovascular events, including stent thrombosis. The clinical availability of ex vivo methods to measure the antiplatelet effect of P2Y12 antagonists raises the possibility that incorporating platelet function testing into clinical practice could facilitate a stratified and efficient approach to antiplatelet therapy following PCI, although data from definitive randomized trials supporting a routine approach are currently lacking.     

Platelet reactivity in stable cardiovascular patients with chronic kidney disease

The study aimed to evaluate antiplatelet drug responsiveness in stable outpatients with cardiovascular disease and chronic kidney disease (CKD) and examine whether impaired antiplatelet drug responsiveness is associated with worse clinical outcomes in this population. Stable cardiovascular patients (n = 771) were enrolled at least one month after an acute ischemic atherothrombotic event. Antiplatelet drug responsiveness was assessed with specific assays (serum TxA₂ for aspirin, the VASP assay for clopidogrel) and other aggregation-based assays using different agonists. All patients were followed until the first occurrence of a major adverse cardiovascular event. The 133 CKD patients were found to have higher activity of von Willebrand factor and higher fibrinogen levels. After a median follow-up of 33 months, 88 events occurred in patients without CKD and 31 events in patients with CKD (5.0 events and 8.7 events per 100 patient years, respectively, HR = 1.75 (95% CI 1.16–2.63; p = 0.008). The prevalence of poor aspirin and clopidogrel responsiveness and high platelet reactivity as assessed with different aggregation-based assays was similar in patients with estimated GFR ≥ 60 ml/min, 45–59 ml/min, and < 45 ml/min. No significant interaction for CKD vs. non-CKD was observed for events occurrence in patients with or without high platelet reactivity on several assays, with the exception of collagen-induced aggregation. In stable cardiovascular patients, CKD is not associated with higher platelet reactivity. Decreased antiplatelet drug responsiveness is not associated with worse clinical outcomes in CKD patients.     

Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study.

OBJECTIVES: We investigated the relation of high ex vivo platelet reactivity, rapid fibrin generation, and high thrombin-induced clot strength to postdischarge ischemic events in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: High platelet reactivity and rapid fibrin generation may affect the incidence of ischemic events after PCI. However, limited data is available to link these ex vivo markers to the occurrence of events. METHODS: We measured platelet reactivity to adenosine diphosphate (ADP) by light transmittance aggregometry (LTA) in patients undergoing PCI (n = 192). Clot strength, a measure of thrombin-induced fibrin and platelet interactions, and the time to initial fibrin generation, a marker of thrombin activity, were measured by thrombelastography. The relation of these measurements to ischemic event occurrence was prospectively examined over six months. RESULTS: A total of 100% and 84% of patients were on aspirin and clopidogrel therapy, respectively, at the time of the initial event. Posttreatment ADP-induced aggregation by LTA (63 +/- 12% vs. 56 +/- 15%, p = 0.02) and clot strength (MA) were higher (74 +/- 5 mm vs. 65 +/- 4 mm, p < 0.001) and time to initial fibrin generation was shorter (4.3 +/- 1.3 min vs. 5.9 +/- 1.5 min, p < 0.001) in patients with events (n = 38). The event rates in the highest quartiles of LTA and MA were 32% and 58%, respectively. CONCLUSIONS: High platelet reactivity and clot strength, and rapid fibrin formation are novel risk factors for ischemic events after PCI. Clot strength is more predictive than ADP-induced platelet aggregation and may explain the occurrence of events despite treatment with cyclooxygenase-1 and P2Y12 inhibitors.     

合并糖尿病或胰岛素抵抗的缺血性卒中患者的抗血小板治疗

糖尿病是缺血性卒中患者抗血小板治疗后发生血小板高反应性的独立预测因素,而后者与卒中复发风险增高密切相关.糖尿病或胰岛素抵抗患者血小板反应性增高的机制与多种因素有关,一些血液循环分子可作为预测血小板反应性增高的标记物.监测新型抗血小板药治疗后的血小板反应性,可为合并糖尿病或胰岛素抵抗的缺血性卒中患者的个体化抗栓治疗提供依据.     

Stent thrombosis and platelet reactivity

Stent thrombosis (ST) is a rare but potentially life-threatening event that can occur following percutaneous coronary intervention (PCI) with stent implantation. Several factors related to the procedure or patient features can favor thrombus formation and development of ST. Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 inhibitors is the cornerstone of strategy for reducing incidence of ST. Two main causes of DAPT failure have been identified: the inappropriately premature antiplatelet therapy discontinuation and hyporesponsiveness to antiplatelet drugs. There is growing evidence that a residual high on treatment platelet reactivity (HPR) is associated with increased risk of thrombotic complications after PCI, including ST. In recent years numerous platelet function tests were developed and some of these have been extensively used in clinical studies to evaluate residual platelet reactivity, after antiplatelet drugs administration. The identification of patients with HPR is fundamental for optimization of antiplatelet treatment. Nevertheless first studies suggested that achieving a more intense platelet inhibition, switching from standard to an intensified treatment regimen on the basis of platelet reactivity, has failed to show any benefit in terms of clinical events. Certainly individualized pharmacological treatment of patients undergoing PCI remains one of the most important objectives in order to prevent serious PCI complications, such us ST.     

Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?

OBJECTIVES: We sought to determine whether patients receiving chronic clopidogrel therapy undergoing nonemergent stenting who display high on-treatment preprocedural platelet aggregation measured by standard light transmittance aggregometry and thrombelastography (TEG) will be at increased risk for poststenting ischemic events. BACKGROUND: Patients exhibiting heightened platelet reactivity to adenosine diphosphate (ADP) might be at increased risk for recurrent ischemic events after coronary stenting. METHODS: A total of 100 consecutive patients receiving chronic antiplatelet therapy consisting of aspirin (325 mg qd) and clopidogrel (75 mg qd) were studied before undergoing nonemergent stenting. Patients were followed for 1 year after coronary stenting for the occurrence of death, myocardial infarction, stent thrombosis, stroke, or ischemia requiring a hospital stay. RESULTS: All patients were aspirin responsive. Patients with ischemic events (23 of 100, 23%) within 1 year had greater on-treatment prestent ADP-induced platelet aggregation than patients without ischemic events by aggregometry and TEG (p < 0.001 for both measurements). Of patients with an ischemic event, 70% and 87% displayed high on-treatment platelet reactivity at baseline by aggregometry and TEG, respectively. High on-treatment platelet reactivity as measured by aggregometry and TEG were the only variables significantly related to ischemic events (p < 0.001 for both assays). The administration of eptifibatide reduced periprocedural elevation in platelet reactivity, with no significant differences in bleeding events. CONCLUSIONS: Patients receiving chronic clopidogrel therapy undergoing nonemergent percutaneous coronary intervention who exhibit high on-treatment ADP-induced platelet aggregation are at increased risk for postprocedural ischemic events. These findings might have implications for the alteration in clopidogrel maintenance dose and use of glycoprotein IIb/IIIa inhibitors in selected patients.     

Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment.

OBJECTIVES: This study sought to assess the influence of type 2 diabetes mellitus (T2DM) and the impact of hypoglycemic treatment (insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy. BACKGROUND: Insulin inhibits platelet aggregation by suppressing the P2Y12 pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12 pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents. Patients with insulin-treated diabetes mellitus (ITDM) have a more advanced disease status and higher atherothrombotic risk compared with non-ITDM (NITDM). However, the impact of insulin therapy on platelet dysfunction in patients treated with P2Y12 antagonists is unknown. METHODS: A total of 201 T2DM and 65 nondiabetic patients with coronary artery disease in a steady phase of aspirin and clopidogrel treatment were studied. Platelet aggregation was assessed using agonists specific (6 and 20 microM adenosine diphosphate [ADP]) and nonspecific (6 microg/ml collagen and 20 microM epinephrine) for the P2Y12 pathway. High shear-induced platelet reactivity was assessed by means of the PFA-100 system (Dade-Behring International, Miami, Florida). RESULTS: The T2DM patients had platelet aggregation and shear-induced platelet function significantly increased compared with nondiabetic patients using all assays. Platelet aggregation was increased in ITDM (n = 68) compared with NITDM (n = 133) patients after P2Y12-specific stimuli. Insulin treatment was the strongest predictor of ADP-induced aggregation. Platelet function profiles were similar between ITDM and NITDM using assays nonspecific to the P2Y12 pathway. Platelet dysfunction was independent of glycemic control and inflammatory status. CONCLUSIONS: The P2Y12-dependent and -independent pathways of platelet reactivity are altered in T2DM compared with nondiabetic patients, and ITDM have greater ADP-induced platelet aggregation compared with NITDM.     

Platelet function monitoring in patients on clopidogrel: What should we learn from GRAVITAS?

Combined inhibition of platelet aggregation is essential to prevent recurrent ischemic episodes in patients with acute coronary syndromes and after percutaneous coronary interventions (PCIs). In combination with aspirin, the ADP receptor antagonist clopidogrel is used widespread for this purpose; however, platelet reactivity after clopidogrel differs substantially between patients and high on-treatment platelet reactivity (HTPR) persists in a substantial proportion of cases. Since more than 20 prior observational studies linked HTPR to higher risk of ischemic events, including cardiovascular death, myocardial infarction, and stent thrombosis, monitoring post-clopidogrel platelet reactivity after PCI might be beneficial for risk assessment and to tailor the antiplatelet therapy to the patients' needs. However, there is no consensus on the role of routine platelet function monitoring in clinical guidelines. This article aims to review the available evidence regarding the clinical relevance of platelet function monitoring, highlighting possible reasons for the controversy between guidelines and observational studies.     

Resistenz gegenüber Plättchenfunktionshemmern: ein reales klinisches Problem

The benefit of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel in cardiovascular risk patients has been documented by several studies. Patients undergoing coronary interventions are in jeopardy of periinterventional thrombotic complications, and stent thrombosis, although a rare event, is still a serious problem, especially in the era of drug-eluting stents. Recently, there is a growing body of evidence that response to antiplatelet therapy is a clinically important entity and subjects presenting a low response to conventional antiplatelet substances are at increased risk for atherothrombotic events. Thereby, aspirin and clopidogrel resistance have been considered a multifactorial phenomenon underlying factors ranging from nonadherence of patients to antiplatelet therapy to demographic characteristics (age, diabetes, renal failure, etc.), acute coronary syndromes as well as genetic polymorphisms involving platelet glycoproteins and cytochrome P450 isoenzymes. The introduction of point-of-care platelet function tests into clinical routine is a still ongoing process, partly because of missing common definitions of resistance, partly due to different laboratory methods that prevent transferability of results. However, first approaches of an adoption of antiplatelet therapy guided by platelet function analysis provide promising results that an individualized antiplatelet strategy might help to improve platelet inhibition in cardiovascular patients. If this will improve clinical outcome has to be evaluated in upcoming studies. The aim of the present article is to give a review about the clinical relevance of resistance to antiplatelet therapy and alternative treatment options.     

微小核糖核酸与抗血小板药物反应异质性的相关研究进展

抗血小板药物在心脑血管血栓性疾病的防治过程中发挥核心作用,但存在药物反应异质性所致的严重缺血/出血风险。寻找能够预测抗血小板药物反应性个体差异的生物标志物,对于个体化应用抗血小板药物具有重要的临床价值。近年研究发现,血小板蕴含丰富的微小核糖核酸(microRNA),其中具有调控血小板P2Y12受体编码基因(P2RY12)表达的microRNA与P2Y12受体拮抗剂抗血小板反应性的相关性备受关注。本文将针对与抗血小板药物反应性相关的血小板microRNA的生物学特征、相关性研究和可能机制作一综述。