Effect Of P2Y12 Inhibitors Research Articles

Effects of antiplatelet therapy on menstrual blood loss in reproductive-aged women: a systematic review

BackgroundThe effects of antiplatelet therapy on menstrual bleeding have not been well characterized. ObjectivesTo systematically review the effects of antiplatelet therapy on menstrual bleeding. MethodsA literature search was performed for studies of reproductive-aged women who received antiplatelet therapy. Characteristics of menstrual bleeding both before and after initiation of antiplatelet therapy and from comparison groups were collected. Two reviewers independently assessed the risk of bias in individual studies. ResultsThirteen studies with a total of 611 women who received antiplatelet therapy were included. Types of antiplatelet drugs used were aspirin (n = 8), aspirin and/or clopidogrel (n = 2), prasugrel (n = 1), and not specified (n = 2). Risk of bias was assessed at moderate (n = 1), serious (n = 8), critical (n = 2), and no information (n = 2). Three studies reported changes in menstrual blood loss volume. One of these showed no increase during antiplatelet therapy; the other 2 studies suggested that aspirin may increase menstrual blood loss volume. In 3 studies that assessed the duration of menstrual bleeding, up to 13% of women reported an increased duration of menstruation. In 5 studies that reported the intensity of menstrual flow, 13% to 38% of women experienced an increase in the intensity of flow. Five studies reported the prevalence of heavy menstrual bleeding in women who received antiplatelet therapy, with estimates ranging from 7% to 38%. ConclusionThere is lack of high-quality data on the effects of antiplatelet therapy on menstrual bleeding. Aspirin may increase menstrual blood loss, at least in a minority of women, whereas the effects of P2Y12 inhibitors are unknown.

Abstract 14457: Safety and Effectiveness of P2Y12 Inhibitors in Critically Ill Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials

Introduction: Critically ill patients with COVID-19 have a high risk of developing thromboembolic events. Randomized controlled trials (RCTs) have shown conflicting results regarding the use of P2Y12 inhibitors in such patients. We conducted a meta-analysis of the available trials. Methods: Studies comparing P2Y12 inhibitors vs control in critically ill patients with COVID-19 were searched from online databases. The primary endpoints of interest were myocardial infarction (MI), systemic arterial thromboembolism, deep venous thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, mortality, and major bleeding at the longest available follow up. Random-effects model was used to calculate risk ratios (RR) with 95% confidence intervals (CI). Results: Three RCTs, with a total of 2,223 patients - 1,084 in the P2Y12 inhibitor group and 1,139 in the control group were included. The mean age was 57 years and 63% of patients were men. The follow up duration varied from 28 to 90 days. The two groups had similar risk of DVT (RR 0.91, 95% CI 0.65-1.28, p = 0.60), ischemic stroke (RR 2.25, 95% CI 0.91-5.55, p = 0.08), MI (RR 1.37, 95% CI 0.54-3.47, p = 0.50), PE (RR 0.95, 95% CI 0.47-1.95, p = 0.90), systemic arterial thromboembolism (RR 1.20, 95% CI 0.24-6.09, p = 0.82), mortality (RR 0.89, 95% CI 0.77-1.03, p = 0.12) (Figure 1) and major bleeding (RR 1.34, 95% CI 0.47-3.78, p = 0.59) (Figure 2). Conclusions: No significant difference was found in venous or arterial thromboembolism, mortality, or major bleeding events in critically ill COVID-19 patients treated with P2Y12 inhibitors as compared to control.

P2Y12 Inhibitors for Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated. Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed. This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24). Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.

Antiplatelet Therapy in Patients With COVID-19—More Is Less?

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Hospitalized Patients With COVID-19

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non–Critically Ill Hospitalized Patients With COVID-19

Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. ClinicalTrials.gov Identifier: NCT04505774.

P2Y12 inhibitors in patients with non-ST-segment elevation acute coronary syndrome: systematic review and network meta-analysis of randomized trials

Abstract Background Based on a recent randomized control trial (RCT), prasugrel is recommended in preference to ticagrelor for patients with non-ST-segment elevation ACS (NSTE-ACS), however, limited data exists. Objectives We aimed to investigate the effect of P2Y12 inhibitors on ischemic and bleeding events in NSTE-ACS patients. Methods Clinical trials enrolling NSTE-ACS patients were identified and relevant data was extracted. We performed a network meta-analysis on efficacy and safety outcomes. Results Our study including a total of 37, 268 patients with NSTE-ACS from 11 RCTs. Prasugrel decreased major adverse cardiovascular events (MACE) when compared to clopidogrel (Hazard ratio (HR): 0.84; 95% confidence interval (CI) [0.71–0.99]). For MACE, prasugrel showed the highest likelihood of event reduction (P-score=0.97) in comparison to ticagrelor (P-score=0.29) and clopidogrel (P-score=0.24). Prasugrel decreased myocardial infarction (HR: 0.82; 95% CI [0.68–0.99]) but increased major bleeding without statistical significance (HR: 1.30; 95% CI [0.97–1.74]) when compared to clopidogrel. Ticagrelor reduced cardiovascular death (HR: 0.79; 95% CI [0.66–0.94]) but increased major bleeding (HR: 1.33; 95% CI [1.00–1.77], p=0.049) in comparison to clopidogrel. There was no significant difference between prasugrel and ticagrelor for each endpoint, but prasugrel had higher likelihood of event reduction than ticagrelor for all endpoints except cardiovascular death. Conclusions Prasugrel and ticagrelor had comparable risk for each endpoint, but prasugrel had the highest probability being the best treatment in reducing the primary endpoint. This study highlights the need for further large-scale RCTs to investigate the optimal P2Y12 inhibitor selection in NSTE-ACS patients. Funding Acknowledgement Type of funding sources: None.

Comparative efficacy and safety of oral P2Y12 inhibitors for patients with chronic kidney disease and acute coronary syndrome: a network meta-analysis

BackgroundCurrently, there is a paucity of data concerning the safety and effectiveness of P2Y12 inhibitors in the acute coronary syndrome (ACS) with chronic kidney disease (CKD) population. The aim of this study is to compare the different oral P2Y12 inhibitors in terms of efficacy and safety, focusing exclusively on patients with CKD who were treated for ACS. MethodsWe systematically searched PubMed, CENTRAL, and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with ACS with CKD. Efficacy outcomes included the major adverse cardiovascular events composite outcome and safety outcomes included major bleedings and major or minor bleedings combined. We performed a frequentist network meta-analysis. ResultsTwelve studies were included in the systematic review, 7 CKD subgroup analyses of RCTs (8878 patients) and 5 observational studies (20175 patients). After the exclusion of studies with conservative management, prasugrel resulted in significant primary endpoint reduction versus clopidogrel (HR 0.80 and 95% CI 0.64 - 0.99), while ticagrelor did not (HR 0.88 and 95% CI 0.73 - 1.06). Major bleedings did not differ between the interventions. Ticagrelor resulted in more major or minor bleedings than clopidogrel (HR 1.21 and 95% CI 1.06 - 1.38), whereas prasugrel did not (HR 1.12 and 95% CI 0.84 - 1.49). ConclusionIn patients with ACS with underlying CKD, who are intended to receive invasive management, there may be a significant reduction of the primary efficacy outcome with prasugrel as compared to clopidogrel but not with ticagrelor as compared to clopidogrel. There probably exists no difference among interventions in the major bleedings. Dedicated RCTs are needed to confirm these results.

The association of P2Y12 inhibitors with pro-coagulatory extracellular vesicles and microRNAs in stable coronary artery disease

Extracellular vesicles (EV) act as a cellular communication tool by carrying lipids, proteins and micro RNA (miR) between cells, thereby playing a pivotal role in thromboembolic processes. The effect of P2Y12 inhibitors on pro-coagulatory, phosphatidylserine (PS)-expressing EV has been investigated previously, but only in vitro or during confounding clinical conditions, such as acute coronary syndrome. Hence, we enrolled 62 consecutive patients 12 month after percutaneous coronary intervention and stent implantation and consequent treatment with dual-antiplatelet therapy consisting of low-dose aspirin and P2Y12 inhibitors. Blood for platelet function testing and EV and miR measurements was taken on the last day of P2Y12 inhibitor intake (baseline, on-treatment) and 10, 30 and 180 days thereafter (off-treatment). We did not observe any influence of P2Y12 inhibitors on the levels of PS-EV or EV sub-population from platelets, erythrocytes, monocytes or endothelial cells, respectively. There was no relationship between platelet function and EV levels in plasma. However, the association of miR-21 and miR-150 with platelet EVs was significantly different between on- and off-treatment measurements. Hence, our study suggests no influence of P2Y12 inhibition on the count of EVs in plasma, but on the potential cargo of platelet-derived EV.

Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study.

BackgroundPrior reports indicate that the effect of P2Y12 inhibitors may be different in East Asian patients (“East Asian paradox”); therefore, understanding the outcomes associated with potent P2Y12 inhibitors in different populations is clinically important.Methods and ResultsIn this observational cohort study using administrative healthcare data sets, we compared safety and effectiveness of contemporary P2Y12 inhibitors in patients with acute coronary syndrome. The primary safety outcomes were major and any bleeding, and the primary effectiveness outcomes were major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) and all‐cause mortality. Among 70 715 patients with acute coronary syndrome, 56 216 (79.5%) used clopidogrel, 11 402 (16.1%) used ticagrelor, and 3097 (4.4%) used prasugrel. The median follow‐up period was 18.0 months (interquartile range: 9.6–26.4 months). In a propensity‐matched cohort, compared with clopidogrel, ticagrelor was associated with a higher risk of any bleeding (hazard ratio: 1.23; 95% CI, 1.14–1.33) but a lower risk of mortality (hazard ratio: 0.76; 95% CI, 0.63–0.91). Prasugrel, compared with clopidogrel, was associated with higher risks of any bleeding (hazard ratio: 1.23; 95% CI, 1.06–1.43) and major bleeding (hazard ratio: 1.50; 95% CI, 1.01–2.21) but a similar risk of effectiveness outcomes. No significant difference was noted between ticagrelor and prasugrel with respect to key safety or effectiveness outcomes. Several sensitivity analyses showed similar results.ConclusionsIn East Asian patients with acute coronary syndrome, compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality. Prasugrel was associated with an increase of any bleeding without difference in effectiveness outcomes. The risks of bleeding and ischemic events were similar between ticagrelor and prasugrel.

Effect of P2Y12 inhibitors on thrombus stability and endogenous fibrinolysis

Although used routinely to reduce thrombotic events in patients with coronary disease, the effects of P2Y12 inhibitors on thrombus stability and endogenous fibrinolysis are largely unknown.Blood taken from patients pre- and post-aspirin (n = 20) and on aspirin alone and on dual antiplatelet therapy comprising aspirin plus clopidogrel (n = 20), ticagrelor (n = 20) or cangrelor (n = 20), was tested using the Global Thrombosis Test. The number of “rebleeds” or drops (D) after early platelet-rich thrombus formation (occlusion time, OT), and before final lasting occlusion, was used as an inverse measure of thrombus stability. Whilst clopidogrel had no effect, ticagrelor and cangrelor both increased D significantly, reflecting increased thrombus instability [D pre- and post-clopidogrel 4.3 ± 1.6 vs. 4.5 ± 1.4, p = 0.833; pre- and post-ticagrelor 4.1 ± 2.4 vs. 6.8 ± 5.1, p = 0.048; pre- and post-cangrelor 3.6 ± 2.0 vs. 7.9 ± 8.9, p = 0.046]. Platelet reactivity was reduced by all P2Y12 inhibitors, demonstrated by OT prolongation (clopidogrel 378 ± 87 s vs. 491 ± 93 s, p < 0.001; ticagrelor 416 ± 122 s vs. 549 ± 121 s, p < 0.001; cangrelor 381 ± 146 s vs. 613 ± 210 s, p < 0.001). The magnitude of OT prolongation compared to baseline (ΔOT) was significantly greater for cangrelor compared to clopidogrel and ticagrelor. Cangrelor was the only agent to enhance fibrinolysis (lysis time pre- and post-cangrelor 1622[1240–2048]s vs. 1388[960–1634]s, p = 0.005).We demonstrate the ability to assess the effect of pharmacotherapy on thrombus stability in vitro and show that P2Y12 inhibitors potentiate thrombus instability at high shear. Cangrelor, and to a lesser extent ticagrelor, de-stabilised thrombus formation and cangrelor also enhanced fibrinolysis. Potentiation of thrombus instability could become a new pharmacological target, that may be particularly important in acute coronary syndromes.

Impact of timing from blood sampling to pharmacodynamic assessment on measures of platelet reactivity in patients treated with P2Y12 receptor inhibitors

Several platelet function tests (PFT) are available to assess the pharmacodynamic (PD) effects of P2Y12 inhibitors. However, there are technical variances between PFT, and P2Y12 inhibitors differ in pharmacological properties. Manufactures of PFT recommend a time-frame within which assessments needs to be executed. However, if the timing from blood sampling to processing affects PD results is unknown. We conducted a prospective study assessing the impact of timing from blood sampling to processing on PD measures using three different PFT. We studied 60 aspirin-treated patients with coronary artery disease (CAD) on maintenance P2Y12 inhibiting therapy [clopidogrel 75 mg/day (n=20), prasugrel 10 mg/day (n=20) and ticagrelor 90 mg bid (n=20)]. PD assessments (trough levels) were performed by VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP) at 30 minutes, 2 and 4 hours post-sampling; VASP was also performed at 24 hours. P2Y12 reaction units (PRU) by VN significantly decreased over time with all P2Y12 inhibitors (clopidogrel p<0.001; prasugrel p=0.016; ticagrelor p<0.001). PRU at 30 minutes and 2 hours were similar, but decreased at 4 hours. LTA showed consistent findings with VN. Conversely, PD measures as assessed by VASP were stable over time (p>0.1 for all P2Y12 inhibitors). In conclusion, in CAD patients on maintenance therapy with P2Y12 inhibitors, timing from blood sampling to processing significantly influences PD measures as assessed by VN and LTA, but not by VASP.

IMPACT OF TIMING FROM BLOOD SAMPLING TO PHARMACODYNAMIC ASSESSMENT ON MEASURES OF PLATELET REACTIVITY IN PATIENTS TREATED WITH P2Y12 RECEPTOR INHIBITORS

Several platelet function tests (PFT) are available to assess the pharmacodynamic (PD) effects of P2Y12 inhibitors. However, there are technical variances between PFT, and P2Y12 inhibitors differ in pharmacological properties. Manufactures of PFT recommend a time-frame within which assessments needs to be executed. However, if the timing from blood sampling to processing affects PD results is unknown. We conducted a prospective study assessing the impact of timing from blood sampling to processing on PD measures using three different PFT. We studied 60 aspirin-treated patients with coronary artery disease (CAD) on maintenance P2Y12 inhibiting therapy [clopidogrel 75 mg/day (n=20), prasugrel 10 mg/day (n=20) and ticagrelor 90 mg bid (n=20)]. PD assessments (trough levels) were performed by VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP) at 30 minutes, 2 and 4 hours post-sampling; VASP was also performed at 24 hours. P2Y12 reaction units (PRU) by VN significantly decreased over time with all P2Y12 inhibitors (clopidogrel p 0.1 for all P2Y12 inhibitors). In conclusion, in CAD patients on maintenance therapy with P2Y12 inhibitors, timing from blood sampling to processing significantly influences PD measures as assessed by VN and LTA, but not by VASP.

158 The Anti-Platelet Effectiveness of P2Y12Receptor Blockade is Strongly Influenced by the Endothelium-Derived Mediators Nitric Oxide and Prostacyclin

Introduction P2Y12 receptor antagonists that block the pro-aggregatory effects of ADP on platelets are commonly prescribed alongside aspirin, as dual antiplatelet therapy (DAPT) for secondary prevention of atherothrombotic events. It is emerging that these agents exert part of their effects through potentiation of the endogenous, endothelial-derived platelet inhibitors, nitric oxide (NO) and prostacyclin (PGI2), which constantly bathe circulating platelets reducing their reactivity through elevating levels of cyclic nucleotides. Thus, if the in vivosynergy between NO and PGI2 amplifies the anti-thrombotic effects of P2Y12 inhibitors, within the circulation variances in the levels of endothelial-derived mediators will be an important determinant of the efficacy of DAPT, suggesting that for the individual patient, endothelial function influences the therapeutic potential of these powerful agents. Here, we characterised the interplay of PGI2, NO and P2Y12 blockade on platelet function. Methods 8 healthy male volunteers received aspirin (75 mg) and prasugrel (10 mg) for 7 days. Platelet responses to TRAP-6 (25 iM) or collagen (4 ig/ml) in the presence of PGI2 (1 nM), NO (100 nM), PGI2+NO or vehicle were assessed by LTA and lumi-aggreggometry. Experiments were replicated in vitro (n = 4) utilising aspirin (30 iM) and prasugrel active metabolite (PAM; 6, 3 or 1.5 iM) representing maximal and partial P2Y12 blockade. Results Ex vivo, prior to DAPT, PGI2, NO, or PGI2+NO had little effect upon platelet aggregation. TRAP-6 (25 iM): vehicle, 74 ± 3%; PGI2+NO, 66 ± 3%. Following DAPT, PGI2 or NO alone caused minor inhibition: vehicle, 57 ± 4%; PGI2, 47 ± 6%; NO 49 ± 6%. Conversely, the combination of PGI2+NO produced strong inhibitory effects, 19 ± 6% (p In vitro, with maximal P2Y12 inhibition (PAM, 6 iM) aggregation to TRAP-6 (25 iM) was reduced: vehicle, 56 ± 5%; PGI2, 30 ± 12%; NO, 46 ± 7%; PGI2+NO, 15 ± 8% (p Conclusion We demonstrate that PGI2 and NO synergise with P2Y12 blockade to produce the greatest platelet inhibition and that platelet reactivity, despite DAPT is powerfully influenced by the presence of NO and PGI2. This highlights that in vivo platelet reactivity will be a function of the level of P2Y12 receptor blockade and levels of extrinsic inhibitory endothelial mediators. This may be relevant to the efficacy of anti-platelet therapies in patients with endothelial dysfunction and introduces the concept of assessing endothelial function in patients undergoingex vivo platelet function testing to help bridge the disconnect between results of platelet testing and thrombotic outcomes.

IMPACT OF MORPHINE ON PHARMACOKINETIC AND PHARMACODYNAMIC PROFILES OF TICAGRELOR IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION

In patients undergoing primary percutaneous coronary intervention (PPCI), morphine delays the pharmacodynamic (PD) effects of P2Y12 inhibitors, including prasugrel and ticagrelor. However, to date studies with novel P2Y12 inhibitors have been limited to PD assessments. The impact of morphine on

Effect of P2Y12 inhibitors on inflammation and immunity.

Platelet P2Y12 inhibitors form a major part of the treatment strategy for patients with acute coronary syndromes (ACS) due to the importance of the platelet P2Y12 receptor in mediating the pathophysiology of arterial thrombosis. It has been increasingly recognised that platelets also have a critical role in inflammation and immune responses. P2Y12 inhibitors reduce platelet release of pro-inflammatory α-granule contents and the formation of pro-inflammatory platelet-leukocyte aggregates. These are important mediators of inflammation in a variety of different contexts. Clinical evidence shows that P2Y12 inhibition by clopidogrel is associated with a reduction in platelet-related mediators of inflammation, such as soluble P-selectin and CD40L, following atherothrombosis. Clopidogrel in addition to aspirin, compared to aspirin alone, also reduces markers of systemic inflammation such as tumour necrosis factor (TNF) α and C-reactive protein (CRP) following ACS. The more potent thienopyridine P2Y12 inhibitor, prasugrel, has been shown to decrease platelet P-selectin expression and platelet-leukocyte aggregate formation compared to clopidogrel. The PLATO study suggested that the novel P2Y12 inhibitor ticagrelor might improve clinical outcomes from pulmonary infections and sepsis compared to clopidogrel in patients with ACS. Ticagrelor is a more potent P2Y12 inhibitor than clopidogrel and also inhibits cellular adenosine uptake via equilibrative nucleoside transporter (ENT) 1, whereas clopidogrel does not. Further examination of the involvement of these mechanisms in inflammation and immunity is therefore warranted.