How to undertake procedures while on antiplatelet agents: a hematologist's view.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally while also contributing to excess health system costs. Significant advancements have been made in the understanding and prevention of deaths from CVD. In addition to risk factor modifications, one of the key developments in this area is the appropriate prescribing of antiplatelet medications for secondary prevention of CVD. With the advent of vascular devices, there has been an increased use of potent antiplatelet agents to mitigate thrombosis risk. A well-recognized, albeit rare complication of antiplatelet drugs is the heightened risk of bleeding. This adverse effect is particularly relevant when a patient receiving these medications may require an urgent surgery. In addition, for elective surgeries, although these drugs can be withheld, there may be some situations when interruption of antiplatelet agents, even for short duration, may lead to thrombotic events. There are no robust guidelines on how to manage these clinical scenarios, although there have been some important studies published recently in this area. In this review, we provide our approach to patients on antiplatelet drugs who may require urgent surgeries or surgical interventions.

Abbreviated ticagrelor based dual antiplatelet therapy in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Few randomized clinical trials have evaluated the safety and efficacy of abbreviated ticagrelor based dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS); however, these trials were underpowered to detect differences in hard clinical outcomes. METHODS: A systematic search of MEDLINE, Cochrane, and Scopus databases was performed through June 2024, for trials that compared abbreviated (≤3-months) versus standard 12-months ticagrelor based DAPT in ACS. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular death, myocardial infarction, stent thrombosis, ischemic stroke, and major bleeding. Endpoints were measured at 12-months after DAPT initiation. Data were pooled using random-effects model. Effect measure utilized was risk ratio (RR). Heterogeneity was assessed via Chi-squared and Higgin's I2 test. RevMan 5.0 (Cochrane Collaboration, Oxford, United Kingdom) was utilized to perform statistical analysis. RESULTS: Five trials were included in this analysis with 21,407 patients assessed. ULTIMATE-DAPT, T-PASS, and GLOBAL LEADERS-ACS assessed 1-month DAPT duration while TICO and TWILIGHT-ACS assessed 3-months DAPT duration. The average age was 62.7 years and 22.7 % were women. ACS presentations included non-ST elevation myocardial infarction (40.1 %), unstable angina (35.2 %), and ST-segment elevation myocardial infarction (31.5 %). Abbreviated ticagrelor based DAPT was associated with lower risk of all-cause mortality (RR 0.78; 95 % Confidence Interval (CI) 0.62-0.98, I2 = 0 %) compared with standard duration DAPT. There was no difference between groups in cardiovascular death (RR 0.65; 95 % CI 0.41-1.03, I2 = 0 %), myocardial infarction (RR 1.04; 95 % CI 0.85-1.27, I2 = 0 %), stent thrombosis (RR 0.97; 95 % CI 0.64-1.45, I2 = 0 %), or ischemic stroke (RR 0.90; 95 % CI 0.62-1.30, I2 = 0 %). Abbreviated DAPT was associated with lower risk of major bleeding (RR 0.50; 95 % CI 0.38-0.66, I2 = 46 %). CONCLUSION: Our analysis includes the totality of randomized data evaluating the merits of abbreviated ticagrelor based DAPT after ACS. The salient study finding was the observed reduced risk of all-cause mortality and major bleeding with abbreviated DAPT approach.

Supporting appropriate use of extended dual antiplatelet therapy post-myocardial infarction based on an innovative 12-month ticagrelor virtual service.

Purpose: Extended dual antiplatelet therapy (DAPT) with ticagrelor and aspirin is recommended in selected cases after myocardial infarction (MI) but not widely deployed in practice. This study assessed an innovative, cardiology pharmacist-led virtual service for determining eligibility for extended DAPT among patients completing 12 months of initial DAPT in primary care following MI. Methods: Within this model, potentially eligible individuals are reviewed virtually by a cardiology pharmacist for suitability for extended DAPT with reduced-dose ticagrelor [60 mg twice daily (BD)] for up to 3 years. Eligibility is guided by the PEGASUS-TIMI 54 trial criteria (aged ≥50 years and having ≥1 high-risk feature for further ischaemic events). This is balanced against potential ineligibility driven primarily by bleeding risk, assessed using PRECISE-DAPT score. The final recommendation is sent to primary care to action. The present work is a retrospective evaluation of patients referred to the service between July 2018 and December 2021. Results: A total of 200 patients were included [n = 131 (65.5%) male; mean age: 69.4 ± 9.5 years]. Of these, 79 (39.5%) were recommended for extended DAPT based on the balance of risks for further ischaemic events vs. bleeding. Sixty-three patients on high-dose DAPT (ticagrelor 90 mg BD)-which is inappropriate beyond 12 months-were reassigned to reduced-dose DAPT or aspirin monotherapy. Conclusions: This virtual clinic played a key role in medicines optimisation, enabling appropriate patients to benefit from extended DAPT while offsetting bleeding risk. The model could be adapted locally for use elsewhere.

Efficacy and safety of ticagrelor monotherapy following a brief DAPT vs. prolonged 12-month DAPT in ACS patients post-PCI: a meta-analysis of RCTs.

BACKGROUND: As per current guidelines, acute coronary syndrome (ACS) patients who undergo percutaneous coronary intervention (PCI) should be started on dual antiplatelet therapy (DAPT) for a period of 12 months. OBJECTIVE: To assess the efficacy and safety of brief DAPT (up to 3 months) succeeded by ticagrelor monotherapy compared with a 12-month DAPT in ACS patients following PCI. METHODS: We systematically searched Cochrane, Embase, and PubMed to find relevant randomized clinical trials. Examined outcomes included the incidence of major adverse cerebrovascular and cardiovascular events (MACCE), bleeding events, and the composite incidence of net adverse clinical events (NACE). RESULTS: Our primary analysis included 21,927 ACS patients from six RCTs. Our pooled results indicate that following PCI in individuals with ACS, brief DAPT followed by ticagrelor did not increase the risk of MACCE (OR 0.92, 95% CI 0.79-1.07) but significantly reduced the risk of minor or major bleeding (OR 0.52, 95% CI 0.44-0.62) and NACE (OR 0.71, 95% CI 0.59-0.86) compared with a long-term DAPT within a follow-up of 12 months. CONCLUSION: Brief DAPT followed by ticagrelor monotherapy is superior to a 12-month DAPT in offering a net clinical advantage in ACS patients following PCI.

Pharmacokinetics and Bioequivalence of a Generic Ticagrelor 90-mg Formulation Versus the Innovator Product in Healthy White Subjects Under Fasting Conditions.

Ticagrelor is a key antiplatelet agent used to prevent thrombotic events in patients with acute coronary syndrome. This open-label, 2-period, crossover Phase I study assessed the pharmacokinetics and bioequivalence of a generic ticagrelor 90-mg formulation compared to the innovator product under fasting conditions. Twenty-eight healthy White adults participated in the study. Each participant received a single dose of either the test or reference formulation, followed by a 7-day washout period before switching to the alternate formulation. Plasma concentrations of ticagrelor were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method. Statistical analysis of primary pharmacokinetic parameters, including maximum concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, showed bioequivalence with test/reference ratios of 110.9% and 107.1%, respectively, and 90% confidence intervals within the 80%-125% regulatory range. Treatment-emergent adverse events, such as headache, dysphagia, and dizziness, were moderate and transient and resolved promptly, with no significant difference in incidence between the formulations. These results confirm that the generic ticagrelor formulation is bioequivalent to the innovator product, supporting its use as an interchangeable option in clinical practice.

Comparison of Ticagrelor with Clopidogrel on Coronary Microvascular Dysfunction Following Acute Myocardial Infarction Using Angiography-Derived Index of Microcirculatory Resistance.

PURPOSE: This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool. METHODS: In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90 mg twice daily, n = 184) or clopidogrel (75 mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up. RESULTS: Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039). CONCLUSION: The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www. CLINICALTRIALS: gov (NCT05978726).

P2Y12-targeted modulation of microglial phenotypes: A novel therapeutic strategy for enhanced axonal regeneration post-spinal cord injury.

AIMS: Microglia activation after spinal cord injury (SCI) is a double-edged sword, modulation of the activated microglia populations toward pro-regenerative phenotypes highlights the potential therapeutic implications. P2Y12, a microglia-specific marker, remains underexplored in its capacity to polarize microglial activation populations in SCI repair. We aimed to explore the effects of modulating P2Y12 on microglia function after spinal cord injury, and further on axonal regeneration and motor recovery after spinal cord injury. MATERIALS AND METHODS: The study employed both in vitro and in vivo models, using BV2 cells and a mouse model of SCI, respectively. Ticagrelor, a P2Y12 antagonist, was administered via a collagen scaffold to ensure stable and sustained release. Transcriptome sequencing analysis, immunofluorescence staining, and Basso Mouse Scale (BMS) scores were used to assess microglial activation, axonal regeneration, and functional recovery. KEY FINDINGS: Herein, we observed P2Y12+ microglia localized predominantly at the lesion periphery within 3 days post injury (dpi), manifesting a pro-inflammatory phenotype, but not anti-inflammatory phenotype. In vitro investigations revealed that P2Y12 inhibition of the activated microglia curtailed pro-inflammatory differentiation while augmenting anti-inflammatory differentiation. SIGNIFICANCE: Leveraging this insight, we engineered a collagen scaffold-based delivery system for sustained release of the P2Y12 antagonist, ticagrelor, at the injury site in a mouse complete SCI model. Notably, P2Y12 suppression markedly enhanced axonal regeneration within the injured site and ameliorated lower limb motor functions in SCI mice. Collectively, our findings illuminate P2Y12-targeted microglial modulation as a promising therapeutic approach for SCI.

Ticagrelor-Related Dyspnea Beyond Adenosine: Insights into Retrotrapezoid Hyperactivity.

Ticagrelor, a P2Y12 receptor antagonist, has been demonstrated to induce dyspnea, which is not associated with cardiac or pulmonary alterations, or metabolic disturbances. The attribution of ticagrelor-related dyspnea to excess adenosine has been widely proposed, yet is not supported by experimental data. In this paper, we put forth a novel hypothesis that the hyperactivity of the retrotrapezoid nucleus, a group of ventral medullary neurons involved in respiratory modulation, is the underlying cause of ticagrelor-related dyspnea. This hypothesis offers a theoretical resolution to the discrepancies and controversies present in previous theories.

Genetic Determinants of Response to P2Y12 Inhibitors and Clinical Implications.

The CYP2C19 enzyme metabolizes clopidogrel, a prodrug, to its active form. Approximately 30% of individuals inherit a loss-of-function (LoF) polymorphism in the CYP2C19 gene, leading to reduced formation of the active clopidogrel metabolite. Reduced clopidogrel effectiveness has been well documented in patients with an LoF allele following an acute coronary syndrome or percutaneous coronary intervention. Prasugrel or ticagrelor is recommended in those with an LoF allele as neither is affected by CYP2C19 genotype. Although data demonstrate improved outcomes with a CYP2C19-guided approach to P2Y12 inhibitor selection, genotyping has not yet been widely adopted in clinical practice.

Randomised Placebo-Controlled Pilot Trial Evaluating the Anti-Anginal Efficacy of Ticagrelor in Patients with Angina with Nonobstructive Coronary Arteries and Coronary Slow Flow Phenomenon.

Background: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterised by the delayed passage of contrast through the coronary arteries, despite the absence of obstructive coronary artery disease (defined as less than 50% narrowing of the vessel lumen). Patients with the CSFP experience recurrent angina, for which there are limited evidence-based therapies. Ticagrelor may serve as an effective anti-anginal therapy for these patients by increasing adenosine levels, which could alleviate coronary microvascular dysfunction and its associated angina due to its vasodilatory properties. This study aimed to determine the anti-anginal efficacy of ticagrelor 90 mg taken twice daily on spontaneous angina episodes in patients with refractory angina (i.e., episodes ≥3/week despite two anti-anginals) and documented CSFP. Methods: In a randomised, double-blind, placebo-controlled, cross-over trial, the anti-anginal efficacy of a 4-week ticagrelor therapy regimen was evaluated in 20 patients with refractory angina (mean age 61.5 ± 10.5 years; 40% women) who had documented slow coronary flow. The primary endpoint was the frequency of angina episodes, recorded using an angina diary. Secondary endpoints included the duration and severity of angina episodes, consumption of short-acting nitrates, and health status evaluations using the Seattle Angina Questionnaire (SAQ) and the Short Form-36 (SF-36) indices. Results: During the four weeks of therapy, ticagrelor did not significantly improve angina symptoms compared to the placebo (placebo 25.7 (16.7)) vs. ticagrelor 19.8 (18.1), p > 0.05). Furthermore, it did not impact other patient-related outcome measures, including angina severity, duration, frequency of prolonged angina episodes, nitrate consumption, or the SAQ/SF-36 health outcome indices. No serious adverse events related to the study drug were observed. Conclusions: In patients with documented CSFP who were unresponsive to standard anti-anginal therapy, ticagrelor did not reduce the frequency of spontaneous angina episodes or the consumption of nitrates. Further confirmation of the potential benefits of this therapy may be obtained through a larger clinical trial.

Aspirin and Ticagrelor Versus Aspirin and Clopidogrel or Prasugrel and the Effect on Staphylococcal-associated Infections: A Real-world Study.

PURPOSE: Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks. METHODS: We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) Staphylococcus aureus bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years. FINDINGS: At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77-0.945; P = 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86-0.91; P < 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87-0.92; P < 0.0001, and (4) Staphylococcus aureus bacteremia (HR = 0.72; 95% CI, 0.61-0.85; P = 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01-1.062; P < 0.0001). IMPLICATIONS: A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in in-vitro studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.

An interesting case series of ticagrelor induced long QTc.

This case series explores three patients who underwent percutaneous coronary intervention (PCI) and experienced prolonged QT intervals under treatment with Ticagrelor. The first case was a female who presented with chest pain and received a Xience stent. The second case involved a male patient who received two Xience stents. The third case was that of a male patient with LAD stenosis. All three patients received Ticagrelor and exhibited prolonged QTc intervals on their electrocardiograms (ECGs), which was resolved after switching to Clopidogrel. Thus far, the potential impact of Ticagrelor on QT prolongation has not been adequately addressed in the literature. It is hypothesized that Ticagrelor can block adenosine uptake by red blood cells, which may explain QTc prolongation. The results of this case series indicate that Ticagrelor may prolong QTc intervals. Consequently, it is imperative that clinicians are aware of this previously unlisted side effect and that patients are closely monitored while seeking alternative medications to manage the condition.

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

Temporal Effect of CYP3A4/5 Induction on Ticagrelor's Pharmacodynamic Effects: A Case Series.

Ticagrelor is contraindicated in combination with cytochrome P450 3A4 and 3A5 enzyme (CYP3A4/5) inducers due to increased clearance, causing diminished antiplatelet effects. The emergent nature of acute coronary syndromes (ACS) may preclude scrutinization of home medications before P2Y12 inhibitor administration. The purpose of this case series is to establish the temporal impact of CYP3A4/5 enzyme induction on ticagrelor's pharmacodynamic effect by utilizing VerifyNow platelet aggregation studies. This was a retrospective case series of three patients who were taking a CYP3A4/5-inducing medication and loaded with ticagrelor for ACS. The duration of ticagrelor's antiplatelet effect was dramatically shortened in the presence of background CYP3A4/5 induction. The offset of antiplatelet effect, defined by platelet reactivity units (PRU), was 10-24 hours in the presence of CYP3A4/5 enzyme induction compared to the anticipated 36-48 hours. This was consistent across CYP3A4/5-inducing medications including carbamazepine, phenobarbital, and phenytoin. This study demonstrates rapid return of platelet function after a ticagrelor loading dose in the presence of CYP3A4/5-inducing medications. Monitoring of PRU every 6-12 hours with subsequent loading with clopidogrel or prasugrel should be considered. Larger scale studies are warranted to confirm these results.

P2Y12 Inhibitor Monotherapy After Short DAPT in Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes. METHODS: Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) versus 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analysis were run to explore whether the effect estimate of each outcomes may be affected by further studies. RESULTS: Seven trials encompassing 27,284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE (OR 0.92, 95% CI 0.76-1.12) and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66) and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (pint=0.016), all-cause death (pint=0.042), NACE (pint=0.018), and myocardial infarction (pint=0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT. CONCLUSIONS: In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE and mortality compared with standard DAPT, supporting its use after aspirin discontinuation. Protocol registration: This study is registered in PROSPERO (CRD42023494797).

Ticagrelor potentiates cardioprotection by remote ischemic preconditioning: the ticagrelor in remote ischemic preconditioning (TRIP) randomized clinical trial.

OBJECTIVE: Remote ischemic preconditioning (RIPC) reduces periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) through various pathways, including an adenosine-triggered pathway. Ticagrelor inhibits adenosine uptake, thus may potentiate the effects of RIPC. This randomized trial tested the hypothesis that ticagrelor potentiates the effect of RIPC and reduces PMI, assessed by post-procedural troponin release. METHODS: Patients undergoing PCI for non-ST elevation acute coronary syndromes were 1:1 randomized to ticagrelor (TG-Group) or clopidogrel (CL-Group). Within each treatment, patients were 1:1 randomized to a RIPC (RIPC-Group) or a control group (CTRL-Group). The primary endpoint was the difference between post- and pre-procedural troponin at 24 h following PCI, termed deltaTnI. RESULTS: During a 12-month period, 138 patients were included in the study (34 in the CL-CTRL group, 34 in the TG-CTRL group, 35 in the CL-RIPC group, and 35 in the TG-CTRL group). There was a significant difference in deltaTnI between the study groups [ TG-RIPC:0.04 (0-0.16), CL-CTRL:0.10 (0.03-0.43), CLRIPC:0.11 (0.03-0.89), and TG-CTRL:0.24 (0.06-0.47); p = 0.007]. Eight patients (22.9%) in the TG-RIPC group developed type 4a myocardial infarction (MI), compared to 14 (40%) in the CL-RIPC group, 13 (38.2%) in the CL-CTRL group, and 19 (55.9%) in the TG-CTRL group (p = 0.048). A significant interaction between antiplatelet group allocation and RIPC on deltaTnI was observed [F (1,134) = 7.509; p = 0.007]. In multivariate analysis, the interaction between RIPC and ticagrelor treatment was independently associated with a lower incidence of Type 4a MI. CONCLUSION: Our results demonstrate an interaction between ticagrelor and RIPC, which may potentiate the cardioprotective effects of RIPC during PCI by reducing PMI.

Ticagrelor 60 vs. 90 mg in Elderly ACS Patients undergoing PCI: a Randomized, Crossover Trial.

AIMS: Although dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remain challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6±4.0 years, females 44%) was included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4±32.1 vs. 30.4±39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; p for non-inferiority=0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29±312.36 ng/mL vs. 579.57±351.73 ng/mL, p=0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg. CONCLUSIONS: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI. Clinical Trial registration: EudraCT 2019-002391-13. Clinicaltrials.gov NCT04739384.

The impact of ticagrelor therapy on CABG-related bleeding in patients with STEMI managed with pPCI and following on-pump CABG.

Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7 days following pPCI) or delayed (> 7 days following pPCI) on-pump CABG surgery were included. All study patients were preloaded with ticagrelor 180 mg prior to pPCI procedure. Patients' demographics, clinical variables, and short-term cardiovascular outcomes were recorded. This is a retrospective study which included 98 patients. Fifty-four (54%) patients underwent early and 44 (45%) patients underwent delayed CABG surgery. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p: 0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level < 10.9 and use of mechanical cardiac support devices were independent predictors of CABG-related bleeding [OR: 3719, p: 0.009 and OR: 11,698, p: 0.004, respectively].There were three deaths within the 30 days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Our results indicated that discontinuation of ticagrelor therapy 3 days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events.

Effects of Body Mass Index and Body Weight on Plasma Concentration of Ticagrelor and Platelet Aggregation Rate in Patients with Unstable Angina in a Chinese Han Population.

Background: The aim of this study was to investigate the impact of body mass index (BMI) and body weight on the concentrations of ticagrelor and the ticagrelor metabolite, AR-C124910XX, as well as the platelet aggregation rate (PAR) in a Chinese Han population with unstable angina (UA). Specifically, it focused on these parameters following the administration of dual antiplatelet therapy (DAPT) comprising aspirin and ticagrelor. Methods: A total of 105 patients with UA were included in the study. Measurement of the platelet aggregation rate induced by adenosine diphosphate (PAR-ADP) was performed before, as well as 3 and 30 days after DAPT treatment. The plasma concentrations of ticagrelor and AR-C124910XX were detected at 3 and 30 days after DAPT treatment. We conducted correlation analyses to assess the effects of BMI and body weight on the concentrations of ticagrelor and AR-C124910XX, on PAR-ADP, and on the inhibition of platelet aggregation induced by adenosine diphosphate (IPA-ADP) at both 3 and 30 days after DAPT treatment. Results: The BMI and body weight were positively correlated with baseline PAR-ADP (r = 0.205, p = 0.007; r = 0.122, p = 0.022). The PAR-ADP at 3 and 30 days after DAPT treatment were significantly lower than at baseline (61.56% ± 10.62%, 8.02% ± 7.52%, 12.90% ± 7.42%, p < 0.001). There was a negative correlation between body weight and the concentrations of ticagrelor and AR-C124910XX at 3 days following DAPT treatment (r = -0.276, p < 0.001; r = -0.337, p < 0.001). Additionally, BMI showed a similar negative correlation with the concentrations of ticagrelor and AR-C124910XX (r = -0.173, p = 0.009; r = -0.207, p = 0.002). At 30 days after treatment, both body weight and BMI were negatively correlated with ticagrelor (r = -0.256, p < 0.001; r = -0.162, p = 0.015) and its metabolite (r = -0.352, p < 0.001; r = -0.202, p = 0.002). Body weight was positively correlated with PAR-ADP (r = 0.171, p = 0.010) and negatively correlated with IPA-ADP (r = -0.163, p = 0.015) at 30 days after treatment. Similarly, BMI was positively correlated with PAR-ADP (r = 0.217, p = 0.001) and negatively correlated with IPA-ADP (r = -0.211, p = 0.001) at the same time point. Conclusions: BMI and body weight are key factors influencing the pharmacokinetics and pharmacodynamics of ticagrelor in Chinese Han patients with UA following DAPT treatment that includes ticagrelor. Both BMI and body weight were positively correlated with PAR-ADP at baseline and 30 days after DAPT treatment. Clinical Trial Registration: ChiCTR2100044938, https://www.chictr.org.cn/.