Antiplatelet options for secondary prevention in acute coronary syndromes

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y(12) inhibitor, for 6?12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y(12) inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS.     

Prasugrel in acute coronary syndrome patients undergoing percutaneous coronary intervention

Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the key treatment strategy for the prevention of ischemic events in patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). However, there is a broad inter-individual response variability to such treatment strategy, and a considerable number of patients persist with inadequate platelet inhibition, which has been associated with an increased risk of ischemic events. Overall, these findings underscore the need for novel antiplatelet agents able to achieve greater platelet inhibition; this can potentially reduce ischemic event rates. Prasugrel (CS-747; LY 640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y₁₂ receptor. Laboratory studies have shown prasugrel to be associated with more prompt, potent and predictable degrees of platelet inhibition compared with clopidogrel. In a large-scale clinical study, which was comprised of high-risk ACS patients undergoing PCI, prasugrel was shown to significantly reduce the short- and long-term risk of ischemic events, including stent thrombosis. However, such significant reduction in ischemic events occurred at the expense of a higher risk of bleeding. Recent clinical trial data analyses have led to a better understanding of the efficacy and safety of prasugrel. This article reviews the currently available data regarding the efficacy and safety of prasugrel in ACS patients.     

Clinical implications of drug–drug interactions with P2Y12 receptor inhibitors

Polypharmacy in patients undergoing coronary artery stenting or in those presenting with an acute coronary syndrome is common. Nevertheless, the risk of drug–drug interactions in patients treated simultaneously with P2Y₁₂ receptor inhibitors is less well considered in routine clinical practice. Whereas the irreversible P2Y₁₂ receptor inhibitors clopidogrel and prasugrel are prodrugs requiring cytochrome P450 (CYP) enzymes for metabolic activation, such activation is not necessary for the direct‐acting reversible P2Y₁₂ receptor inhibitor ticagrelor. Several drugs frequently used in cardiology have been shown to interact with the metabolism of P2Y₁₂ receptor inhibitors in pharmacodynamic studies. Whereas several drug–drug interactions have been described for clopidogrel and ticagrelor, prasugrel seems to have a low potential for drug–drug interactions. The clinical implications of these interactions have raised concern. In general, concomitant administration of P2Y₁₂ receptor antagonists and strong inhibitors or inducers of CYP3A/CYP2C19 should be performed with caution in patients treated with clopidogrel/ticagrelor. Under most circumstances, clinicians have the option of prescribing alternative drugs with less risk of drug–drug interactions when used concomitantly with P2Y₁₂ receptor inhibitors.     

Dual Antiplatelet Therapy: Guidance for Nurse Practitioners

Long-term dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is recommended after acute coronary syndrome (ACS) to reduce the risk of secondary ischemic events. DAPT is recommended for at least 12 months after ACS, with prolonged DAPT suggested in patients with low bleeding risk. Nurse practitioners have an important role in managing patients after ACS, acting as patient advocates and collaborating with the cardiology provider to ensure adherence to DAPT. This review describes current recommendations for DAPT in patients with ACS and the nurse practitioners role in maximizing benefits of antiplatelet therapy.     

Oral antiplatelet agents in ACS: from pharmacology to clinical differences

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Numerous clinical trials have established the value of antiplatelet therapies for ACS. Aspirin (ASA), thienopyridines and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Recently, a third generation of thienopyridines has been introduced represented by prasugrel that has demonstrated promising results in ACS patients treated with percutaneous coronary intervention (PCI). A number of nonthienopyridine oral antiplatelet drugs are under development, and one of them, ticagrelor has already been tested in a major phase III clinical trial, PLATO, with the inclusion of a broad spectrum of patients with ACS. The present review aims to discuss the present knowledge about the safety and efficacy of oral antiplatelet treatment of patients with ACS.     

Antiplatelet therapy - ticagrelor

Ticagrelor, a cyclopentyltriazolopyrimidine (CPTP), is the representative of a new chemical class of P2Y(12) receptor inhibitors that differ from thienopyridines (ticlopidin, clopidogrel, prasugrel) as ticagrelor is not a prodrug requiring active biotransformation by cytochromes in the liver and thus is characterized by a more rapid, more effective and more consistent platelet inhibition than ticlopidin or clopidogrel. An extensive study program for dose finding and safety for AZD6140 (DISPERSE studies) and a large-scaled phase III trial (PLATO) were undertaken on more than 18,000 patients for validation of efficacy and safety. In the PLATO trial, patients presenting with the broad spectrum of ACS, i.e. unstable angina, non-STEMI or STEMI, were randomized to ticagrelor (Brilique, Brilinta) or clopidogrel within 24 hours after onset of symptoms, regardless whether they were allocated to a planned invasive or conservative treatment. Compared to clopidogrel, ticagrelor reduced rates of the primary endpoint consisting of cardiovascular death, non-fatal MI, or stroke, without an excess of the primary safety endpoint that was PLATO-defined major bleedings. Results from the pre-specified confirmatory subgroup of patients undergoing planned invasive treatment was consistent with PLATO main trial. In addition, the primary endpoint, as well as CV death and all cause death were consistently reduced with ticagrelor in numerous exploratory subgroups including STEMI patients, those planned for non-invasive treatment, patients undergoing CABG, patients with renal failure, and those with diabetes mellitus, although patients were pretreated before coronary angiography and patients with clopidogrel pretreatment were not excluded. CONCLUSIONS: The pharmacological properties and convincing study results of the PLATO trial have stimulated a paradigm change for dual antiplatelet therapy. The new ESC guidelines on the management of ACS without ST segment elevation recommend the use of clopidogrel only when a new antiplatelet drug, e.g. ticagrelor or prasugrel is not available or contraindicated.     

New P2Y12 blockers

Summary.  A number of new antiplatelet agents currently in development are anticipated to improve clinical outcomes and safety benefits in patients with acute coronary syndrome (ACS). This article reviews the pharmacology and clinical development of three of these agents: prasugrel, cangrelor, and ticagrelor. Prasugrel, a third-generation, oral thienopyridine, has been shown to be superior to clopidogrel, the current gold standard, in preventing ischemic events in patients with ACS undergoing percutaneous coronary intervention (PCI), although the bleeding rate was higher. Cangrelor, a chemical analog of adenosine triphosphate, is a potent direct platelet P2Y₁₂ antagonist. In development as an intravenous agent, cangrelor is currently being evaluated in two phase III studies in patients requiring PCI. Ticagrelor is the first of a new class of orally available antiplatelet agents antagonizing the effects of ADP mediated by P2Y₁₂; it is currently being studied in a phase III trial in patients with ACS.     

The evolution of dual antiplatelet therapy in the setting of acute coronary syndrome: ticagrelor versus clopidogrel

Review of: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Eng J Med 2009; 361(11): 1045–1057.

For acute coronary syndrome (ACS), a dual antiplatelet regimen comprised of treatment with aspirin and either P2Y12 adenosine diphosphate receptor antagonists, clopidogrel, prasugrel or ticagrelor is usually employed. This article compares clopidogrel with ticagrelor for the prevention of vascular events and death in broad population of ACS patients ranging from UA, NSTEMI to STEMI, utilizing planned strategies of medical or invasive treatment strategy.     

Antiplatelet function variability in clopidogrel-treated patients: need for new antiplatelet agents

Antiplatelet therapy is obligatory in patients with coronary artery disease (CAD) both in acute coronary syndromes (ACS) and in secondary prevention. Aspirin in combination with clopidogrel has been recommended as the main therapeutic regimen for many years. However, the high inter-individual variability of platelet aggregation seen with clopidogrel, caused by the underlying disease (more pronounced in diabetic patients and patients with ACS), drug interactions as well as by genetic variants leading to a reduced formation of the active metabolite of the prodrug clopidogrel, has confronted clinical practice with increasing numbers of adverse clinical events in patients following an ACS. Therefore, new antiplatelet agents have been investigated showing a more favorable efficacy/safety profile. Prasugrel as well as ticagrelor are meanwhile part of the recently published revascularization guidelines of the European Society of Cardiology based on their favorable results with respect to reducing a combined ischemic efficacy endpoint in patients with ACS in the TRITON-TIMI-38 (prasugrel) and PLATO (ticagrelor) trials. Different to clopidogrel, their effects are independent of genetic variants and also drug interactions seem neglectable. This article discusses the reasons for antiplatelet function variability of clopidogrel and presents clinical data of the new ADP-receptor inhibitors by reviewing the recently published trials and prespecified post hoc analyses of these trials as well as the potential use of the new antiplatelet agents in the near future.     

Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients With Diabetes

OBJECTIVE

It has been postulated that prasugrel might be the preferred treatment option in diabetes mellitus (DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to compare the pharmacodynamic action of ticagrelor versus prasugrel.

RESEARCH DESIGN AND METHODS

In a prospective, single-center, single-blind, crossover study, 30 consecutive ACS patients with DM who had been pretreated with clopidogrel were randomized to either 90 mg ticagrelor twice daily or 10 mg prasugrel once daily with a 15-day treatment period. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay, measured in P2Y12 reaction units (PRU).

RESULTS

PR was significantly lower after ticagrelor (45.2 PRU [95% CI 27.4–63.1]) compared with prasugrel (80.8 PRU [63.0–98.7]), with a least squares mean difference of –35.6 PRU (−55.2 to −15.9, P = 0.001). High PR rate was 0% for ticagrelor and 3.3% for prasugrel (P = 1.0).

CONCLUSIONS

In DM patients with ACS who had been pretreated with clopidogrel and who undergo PCI, ticagrelor achieves a significantly higher platelet inhibition than prasugrel. Both antiplatelet agents effectively treat high PR. The relevance of these findings to the clinical efficacy and safety of ticagrelor and prasugrel in DM patients needs further elucidation.Patients with diabetes mellitus (DM) suffering from acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI) have an increased platelet reactivity (PR) and prothrombotic potential, a lower response to clopidogrel, and a higher risk of cardiovascular complications and recurrent atherothrombotic events than non-DM patients (1–8).Prasugrel and ticagrelor are newer and more potent than clopidogrel antiplatelet agents, which have been introduced recently into our armamentarium while treating ACS patients undergoing PCI (9,10). In the Prasugrel Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS-3) study, in patients with DM and coronary artery disease (CAD), prasugrel provided a higher inhibitory platelet activity than high-dose clopidogrel (11). A prespecified, subgroup analysis of the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed that prasugrel significantly reduced the incidence of the composite of cardiovascular death, myocardial infarction, and stroke compared with clopidogrel (12.2 and 17.0%, respectively, HR 0.70; P < 0.001) among DM patients, although without significant DM status-by-treatment interaction (12). Of note, no benefit on mortality was observed with prasugrel over clopidogrel. Furthermore, in the subgroup analyses of the Platelet Inhibition and Patient Outcomes (PLATO) trial, the reduction in the primary composite end point, all-cause mortality, and stent thrombosis with no increase in major bleeding in DM patients by ticagrelor was consistent with the overall cohort (3,13). While interpreting the above subanalyses, it has been proposed that prasugrel may be the preferred treatment option in DM patients (14), although a word of caution has been raised by others for comparison between PLATO and TRITON regarding early ischemic events in such patients (3).There are no direct clinical outcome comparisons of ticagrelor versus prasugrel. In a pharmacodynamic comparison of ticagrelor versus prasugrel in ACS patients undergoing PCI and exhibiting high PR (HPR) while on clopidogrel, ticagrelor reduced PR to a lower level than prasugrel (15). In ST segment elevation myocardial infarction patients undergoing primary PCI, both ticagrelor and prasugrel appeared similarly effective in reducing PR during the first 24 h, with lower PR achieved with ticagrelor than prasugrel at day 5 (16). In the current study, we aimed to compare the pharmacodynamic action of ticagrelor versus prasugrel in DM patients with ACS undergoing PCI who had been pretreated with clopidogrel.     

New Antiplatelet Agents and the Role of Platelet Function Testing in Acute Coronary Syndromes

Background

Dual antiplatelet therapy is a guideline mandated for patients with acute coronary syndromes (ACS). Despite its use, thrombotic events continue to occur both early and late. Platelet function testing has been used to define the in vitro effects of new antiplatelet agents, and it has been suggested that it be used to choose therapy. The role of platelet function testing, particularly with newer antiplatelet agents, remains unclear.

Objective

We review the rationale for platelet function testing and its application in monitoring patients on antiplatelet therapy. We also review recent clinical trials of newer antiplatelet agents. On the basis of this review, we reach conclusions on the current role of antiplatelet function testing in monitoring modern antiplatelet therapy and the role of the new antiplatelet agents in the treatment of ACS.

Methods

We reviewed recent publications on platelet function testing and clinical trials of newer antiplatelet therapies compared with clopidogrel.

Results

Platelet function testing is complex, but there is now a bedside test, VerifyNow. High platelet reactivity has been associated with worse cardiovascular outcomes in patients undergoing percutaneous coronary intervention. Recent clinical trials have not found any advantage in outcomes in patients who have their therapy adjusted by monitoring their platelet function. Newer agents, prasugrel, ticagrelor, and cangrelor, produce more rapid, complete, less variable effects on platelet function than clopidogrel. Prasugrel was found to improve outcomes compared with clopidogrel in patients with ACS undergoing percutaneous intervention. Ticagrelor is beneficial in all patients with ACS and reduces cardiovascular mortality compared with clopidogrel. Cangrelor improves outcomes in patients undergoing stenting. Recent studies to assess the role of platelet function monitoring of the effects of clopidogrel and modifying treatments have not been successful.

Conclusion

Recent clinical trials have indicated that newer antiplatelet agents have advantages over clopidogrel in the treatment of ACS. Platelet function testing gives us a guide to the timing, efficacy, and variability of therapy and can correlate with poor patient outcomes; however, the use of antiplatelet function testing to tailor therapy does not seem appropriate.     

Acute coronary syndromes: identifying the appropriate patient for prasugrel

Acute coronary syndrome (ACS) remains the leading cause of morbidity and mortality. More than half of patients presenting with ACS will experience a recurrent ischemic event; thus, preventing recurrent events is essential to reduce morbidity and mortality associated with ACS. While dual antiplatelet therapy with aspirin and clopidogrel has been the foundation of management for patients presenting with ACS, clopidogrel is limited by delayed antiplatelet effect and a variable patient response. Prasugrel is more potent, has a more rapid and consistent antiplatelet effect, and has been associated with improved outcomes compared with clopidogrel in select patients with ACS. Although prasugrel reduces the risk of recurrent cardiovascular events, it also increases the risk of major bleeding. Careful patient selection will improve the likelihood that patients treated with prasugrel will experience the benefit of this antiplatelet agent with the lowest possible risk of an adverse event. This article reviews the data supporting the use of prasugrel in ACS with an emphasis on characteristics that will help identify the most appropriate patient for this therapy.     

Reviewing the controversy surrounding pre-treatment with P2Y12 inhibitors in acute coronary syndrome patients

Pretreatment with oral P2Y₁₂ inhibitors occurs each time clopidogrel, prasugrel, ticagrelor are given to patients with suspected coronary artery disease before definition of the coronary anatomy. In acute coronary syndromes, the practice of administering oral P2Y₁₂ inhibitors upstream has been the object of significant controversy in recent years, following the publication of two trials of pretreatment in non-ST-segment elevation acute coronary syndromes and ST-segment elevation myocardial infarction, respectively. The introduction in the market of cangrelor - the first intravenous P2Y₁₂ inhibitor – represents a new opportunity but also a new challenge for clinicians. This article reviews current recommendations and supporting evidence surrounding pretreatment with oral and intravenous P2Y₁₂ inhibitors in patients with acute coronary syndromes.     

P2Y₁₂ receptor inhibitors: integrating ticagrelor into the management of acute coronary syndrome

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y?? receptor inhibitors. While clopidogrel remains the "workhorse" P2Y?? receptor inhibitor for many patients with ACS and prasugrel has an established role in select situations, clinicians must now assimilate the evolving role of ticagrelor. Although ticagrelor offers important advances in the management of ACS (eg, reversibility), there are also notable clinical considerations (eg, unique adverse effects such as dyspnea). Based on the current evidence, we propose an algorithm to aid clinicians in the selection of a P2Y?? receptor inhibitor for patients with ACS in various clinical situations.     

Evaluating the risk-benefit profile of the direct-acting P2Y(12) inhibitor ticagrelor in acute coronary syndromes

Ticagrelor is a direct-acting, oral, reversibly binding P2Y(12) receptor antagonist. As a cyclopentyltriazolopyrimidine, ticagrelor represents a new chemical class of agents that do not require metabolic activation and have consistent ability to inhibit platelet aggregation. The phase 3 PLATelet Inhibition and Patient Outcomes (PLATO) trial (NCT00391872) evaluated ticagrelor compared with clopidogrel in 18 624 patients with acute coronary syndromes (ACS), and demonstrated a significant reduction in the risk of death from vascular causes/myocardial infarction (MI)/stroke with ticagrelor (9.8% vs 11.7% with clopidogrel [hazard ratio, 0.84; 95% confidence interval, 0.77-0.92]; P < 0.001) without a significant increase in PLATO-defined major bleeding (11.6% vs 11.2%, respectively; P = 0.43). Myocardial infarction and death from vascular causes were separately significantly reduced, and death from any cause and stent thrombosis reductions achieved nominal statistical significance. Ticagrelor showed benefit over clopidogrel in almost all patient subgroups, including patients who had previously received clopidogrel, patients with both planned invasive or noninvasive treatment, patients with ST-segment elevation MI (STEMI) referred for primary percutaneous coronary intervention, patients with non-STEMI, and patients who underwent bypass surgery. Hence, the PLATO population reflected specifically those patients who would ordinarily receive thienopyridine-based antiplatelet therapy in a clinical setting. Although there are limitations in directly translating trial findings to clinical practice, the findings of PLATO suggest that for every 1000 ACS patients admitted to hospital, using ticagrelor instead of clopidogrel for 12 months would result in 14 fewer deaths or 11 fewer MIs. This review places the PLATO data in context, and assesses the role that ticagrelor may play in treating patients with ACS.     

Unmet needs in oral antiplatelet therapy with ADP receptor blocking agents

Antiplatelet agents like aspirin and clopidogrel are treatment cornerstones for acute coronary syndromes (ACS). Drawbacks of dual therapy with these agents include slow onset and offset of effect and wide response variability. Clopidogrel may provide little benefit if administered too close to percutaneous coronary intervention (PCI) and increase major bleeding risk if given too close to coronary artery bypass grafting (CABG) or other surgery. It may not provide sufficient antiplatelet coverage prior to CABG if stopped too long before intervention and leave patients without antiplatelet coverage due to hyporesponsiveness. Prasugrel has made steps towards addressing these limitations by exhibiting more efficient metabolism, more rapid onset of effect, and greater and more consistent platelet inhibition than clopidogrel. The TRITON-TIMI38 trial in ACS patients undergoing PCI showed prasugrel produced greater ischemic event protection than clopidogrel but significantly increased major bleeding risk. AZD6140, the first reversible oral P2Y₁₂ inhibitor, provides more rapid onset of effect and greater and more consistent platelet inhibition than clopidogrel. In DISPERSE2, a phase II trial in ACS patients, AZD6140 did not increase bleeding risk, reduced bleeding risk among CABG patients, and produced numerical reductions in myocardial infarction risk. AZD6140 is being compared with clopidogrel in PLATO, a phase III trial in approximately 18000 ACS patients.     

Cangrelor: a review on its mechanism of action and clinical development

In patients with acute coronary syndromes and undergoing percutaneous coronary intervention, numerous large-scale clinical trials have shown that adjunctive treatment with the P2Y₁₂ receptor antagonist clopidogrel in addition to aspirin reduces ischemic events. These studies underscore the importance of blockade of the P2Y₁₂ signaling pathway in these settings. However, recent findings have shown that clopidogrel therapy may have some shortcomings. These include its broad range of interindividual-response profiles, where patients with low P2Y₁₂ inhibitory effects have an increased risk of recurrent ischemic events, including stent thrombosis, and its irreversible mechanism of action. These observations underscore the need for novel antiplatelet agents overcoming these limitations. Cangrelor (AR-C69931MX) is an intravenous, direct-acting and reversible P2Y₁₂ receptor antagonist. Cangrelor has a rapid onset and offset of action and achieves significantly greater degrees of platelet inhibition compared with clopidogrel. This article provides an overview of the current status of knowledge on cangrelor, focusing on its pharmacologic properties, clinical development and potential future applications.     

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)?

The FDA has approved ticagrelor (Brilinta-AstraZeneca), an oral antiplatelet drug, for use with low-dose aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It will compete with clopidogrel (Plavix) and prasugrel (Effient) for such use. Clopidogrel is expected to become available generically in the US within the next few months.     

替格瑞洛治疗氯吡格雷低反应患者的有效性及安全性分析

目的 观察替格瑞洛对氯吡格雷低反应急性冠状动脉综合征(acute coronary syndromes,ACS)患者治疗的有效性及安全性。方法 选择2013年1月至2014年6月应用氯吡格雷75 mg/d治疗的ACS经皮冠状动脉介入治疗(PCI)术后患者493例,用血栓弹力图测定血小板聚集率,根据血小板聚集率筛选出氯吡格雷低反应患者173例,采用数字随机法分为氯吡格雷组(n=87)和替格瑞洛组(n=86)。氯吡格雷组继续服用氯吡格雷(75 mg/d),替格瑞洛组将氯吡格雷替换为替格瑞洛(90 mg,2次/d)。主要终点事件为治疗3天、7天、30天二磷酸腺苷(ADP)诱导的血小板聚集率变化情况,次要终点事件为主要不良心脑血管事件(MACCE)及出血的发生率。结果 替格瑞洛组3天、7天、30天血小板聚集率分别为(56.7±12.5)%、(54.1±12.3)%、(53.2±15.3)%显著低于氯吡格雷组(87.7±14.3)%、(85.4±12.7)、(84.9±10.7)%,差异有统计学意义(P<0.01)。对所有患者随访12个月,替格瑞洛组MACCE及出血的发生率显著低于氯吡格雷组(P<0.05)。而两组出血发生率差异无统计学意义(P＞0.05)。结论 对于经皮冠状动脉介入治疗的氯吡格雷低反应患者接受替格瑞洛治疗后能获得理想的抗血小板效果,且替格瑞洛是有效、安全可信赖的药物。