Does one size really fit all? The case for personalized antiplatelet therapy in interventional cardiology.

Cardiovascular disease is the leading cause of death worldwide. Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor, is currently recommended as a default for patients after acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). However, controversies arise over the role of aspirin, the optimal duration of DAPT after drug-eluting stent (DES) implantation, the choice of P2Y12 inhibitor and the variability in individual responses to antiplatelet agents. Recent data indicate that monotherapy with a P2Y12 inhibitor may have adequate anti-ischemic effects with lower bleeding risk. Additionally, discrepancies in DAPT duration recommendations and the optimal P2Y12 inhibitor, provides more uncertainty. We ask the question "does one size really fits all?" or should a more personalized strategy should be implemented.

Diseases affecting the heart and blood circulation are the leading cause of death worldwide. Treatment with drugs that prevents platelets from clumping (called antiplatelets) like aspirin plus another drug group (called P2Y12 inhibitors) like clopidogrel, ticagrelor and prasugrel, is currently recommended as a default for patients after heart attack and/or in whom coronary stents are inserted. However, it is very well documented that the response of any individual to these drugs is highly variable, and that the patients who don't respond as well to them are at increased risk of having clot events in their coronary arteries. On the other hand, people who respond to the drugs very sensitively have a higher bleeding risk. Despite these observations, there is no attempt to test the response of individuals patients to their antiplatelet drugs in routine practice. This review article looks in detail and whether the currently used strategy of "One size fits all" should be changed, given that there may well now be the chance to perform routine testing on everyone, and personalize their treatment accordingly.

Navigating Aspirin Hypersensitivity in Patients Undergoing Percutaneous Coronary Intervention.

Aspirin hypersensitivity continues to be a major clinical challenge in patients with coronary artery disease (CAD), particularly in those requiring percutaneous coronary intervention (PCI) in the absence of a validated alternative antiplatelet regimen. Although true aspirin allergies are uncommon, they can manifest with severe reactions such as angioedema or anaphylaxis, highlighting the critical role of diagnostic challenge tests and tolerance induction strategies. Here, a 61-year-old female with end-stage renal disease (ESRD) on hemodialysis presented with new-onset heart failure and elevated troponins in the setting of a hypertensive emergency. A subsequent left heart catheterization revealed severe multivessel disease, but PCI was deferred due to her history suggestive of aspirin-induced angioedema and the absence of a known optimal approach in this scenario. Given the feasibility of completing a desensitization protocol, aspirin desensitization was pursued, facilitating the successful placement of a drug-eluting stent. This case highlights the need for validated protocols to manage aspirin hypersensitivity, as the current treatment paradigm necessitates a highly individualized approach by the treating clinician.

Early detection of resistance to dual antiplatelet therapy in patients who have undergone percutaneous coronary intervention using the VerifyNow test and associated factors.

Resistance to dual antiplatelet therapy (DAPT), including aspirin and clopidogrel, in patients who have undergone percutaneous coronary intervention (PCI) leads to the inability to prevent thrombotic complications. The present study aimed to evaluate early resistance to aspirin and clopidogrel in patients following PCI using the VerifyNow test and associated factors. A total of 50 patients diagnosed with acute coronary syndromes (ACS) who underwent emergency PCI and received DAPT were recruited in the present study. The detection of resistance to aspirin and clopidogrel was performed using the VerifyNow system. Resistance to aspirin was determined with VerifyNow Aspirin >550 aspirin reaction units (ARU). Resistance to clopidogrel was determined with VerifyNow P2Y12 >208 P2Y12 reaction units (PRU). The resistance rate to aspirin was 14%, while the resistance rate to clopidogrel was higher, at 34%. There were 2 patients with resistance to aspirin and clopidogrel (4%). Univariable logistic regression analysis revealed that diabetes, the use of ß-blockers, and low levels of hemoglobin and hematocrit were associated with resistance to clopidogrel. Following multivariable logistic regression analysis, only the use of ß-blockers was truly associated with resistance to clopidogrel. On the whole, the results of the present study may also prove to be helpful in the selection of therapeutic drugs for patients undergoing PCI and who are diagnosed with ACS.

Diagnostic Yield and Outcomes of Small Bowel Capsule Endoscopy in Patients with Small Bowel Bleeding Receiving Antithrombotics.

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient's bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.

Evidence for routine brain-to-pelvis imaging and antiplatelet therapy in patients diagnosed with fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a disease of the musculature of arterial walls leading to stenoses, aneurysms, and dissections. The purpose of this report was to summarize the evidence for (1) one-time routine imaging from brain-to-pelvis and (2) lifelong antiplatelet therapy, for example, aspirin, for patients diagnosed with FMD as suggested by an international consensus report from 2019. PubMed was systematically searched, and the evidence providing a basis for the current consensus points, as well as articles published since, were reviewed. In four registries evaluating patients with FMD, the prevalence of multivessel involvement, aneurysms, and dissections was reported to be 43.5%-66.3%, 21.6%-30.6%, and 5.6%-28.1%, respectively. Any antiplatelet drug was used in 72.9% of patients, and aspirin was prescribed in up to 70.2% of patients. Based on the high prevalence of vascular manifestations, their associated morbidity, and the potential for endovascular or surgical intervention, the suggestion of one-time brain-to-pelvis screening with computed tomography angiography or magnetic resonance angiography is well supported. Contrarily, the evidence to support the consensus statement of lifelong antiplatelet therapy to all patients in the absence of contraindications is more uncertain since a beneficial effect has not been demonstrated specifically in patients with fibromuscular dysplasia. Therefore, until the efficacy and safety of primary thromboprophylaxis have been demonstrated in this patient group specifically, it may be equally appropriate to only use antiplatelet agents in patients with a clear indication after individual evaluation according to risk factors for thrombotic and thromboembolic complications.

The influence of P2Y12 gene polymorphisms on clopidogrel therapy in patients after percutaneous coronary intervention.

Aim: We aimed to define the influence of P2Y12 polymorphisms (rs6801273, rs2046934, and rs6809699), diabetes, hypertension, obesity, hypercholesterolemia, statins intake, and smoking habit on clopidogrel therapy in patients undergoing percutaneous coronary intervention. Materials & methods: We used PCR-RFLP and PCR-ASO for P2Y12 genotype analysis. The effectiveness of the therapy was measured with the VerifyNow method and defined in platelet reactivity units. Results: Studied polymorphisms had no statistically significant influence on PRU before (PRU0) and 6 months (PRU6) after the procedure. H1/H1 diabetic carriers had significantly higher PRU6 values than patients without diabetes. Obese H1/H2 subjects had significantly lower PRU6 values than H1/H2 non-obese carriers. Conclusion: We found that obesity and diabetes may influence the long-term outcome of antiplatelet therapy.

Clopidogrel is a medicine that prevents platelets in the blood from clumping and blocking arteries. When the structure of the protein (e.g., P2Y12), responsible for response to clopidogrel is changed, we can observe less efficient therapy. Said changes can be caused for example by genetic polymorphisms, which are two or more variants of the same gene. This is why we wanted to check the impact of P2Y12 polymorphisms. We also wanted to check the impact of diabetes, high blood pressure, being overweight, high cholesterol blood level, cholesterol-reducing drugs, and smoking habits on clopidogrel treatment in patients after a procedure that unblocks blood vessels of the heart to restore its blood supply (percutaneous coronary intervention). We measured the efficacy of the treatment with platelet reactivity units (PRU). Studying polymorphisms had no impact on treatment efficacy before (PRU0) and 6 months (PRU6) after the medical procedure. We found that diabetes can cause higher platelet reactivity after 6 months of therapy. We noticed that being overweight may also be important, as obese patients had lower platelet reactivity values.

Predictors of symptomatic intracerebral hemorrhage after endovascular treatment for acute ischemic stroke due to tandem lesion in anterior circulation.

BACKGROUND: Endovascular treatment (EVT) of tandem lesion (TL) in the anterior circulation acute ischemic stroke (IS) usually requires periprocedural antithrombotic treatment and early initiation of dual antiplatelet therapy (DAPT) after carotid stenting. However, it may contribute to an occurrence of symptomatic intracerebral hemorrhage (SICH) in some cases. We investigated factors influencing the SICH occurrence and assessed the possible predictors of SICH after EVT. METHODS: IS patients with TL in the anterior circulation treated with EVT were enrolled in the multicenter retrospective ASCENT study. A good three-month clinical outcome was scored as 0-2 points in modified Rankin Scale (mRS) and recanalization using the TICI scale. SICH was assessed using the SITS-MOST criteria. Logistic regression analysis was used for the assessment of possible predictors of SICH with adjustment for potential confounders. RESULTS: In total, 300 (68.7% males, mean age 67.3 ± 10.2 years) patients with median of admission NIHSS 17 were analyzed. Recanalization (TICI 2b-3) was achieved in 290 (96.7%) patients and 176 (58.7%) had mRS 0-2. SICH occurred in 25 (8.3%) patients. Patients with SICH did not differ from those without SICH in the rate of periprocedural antithrombotic treatment (64 vs. 57.5%, p=0.526) and in the rate of DAPT started within the first 12 hours after EVT (20 vs. 42.2%, p=0.087). After adjustment, admission NIHSS and admission glycemia were found as the only predictors of SICH after EVT. CONCLUSION: Admission NIHSS and glycemia were found as the only predictors of SICH after EVT for TL. No associations between periprocedural antithrombotic treatment, early start of DAPT after EVT and SICH occurrence were found.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Effects of dual antiplatelet therapy (DAPT) compared to single antiplatelet therapy (SAPT) in patients with traumatic brain injury.

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

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).

Left main coronary artery disease treated with beating heart surgery: 10-year single center results.

Introduction: Left main (LM) coronary disease is believed to represent a complex, advanced, and potentially life-threatening atherosclerotic syndrome that can be treated by either percutaneous or surgical interventions. Despite its satisfactory results, the declined number of off-pump coronary artery bypass grafting (OPCAB) is observed. Aim: To compare 10-year survival and point out possible mortality risk factors in patients referred for left main and multivessel OPCAB surgery followed by transit time bypass measurements. Material and methods: There were 159 patients (128 (81%) men and 31 (19%) women) in a median age of 66 (60-70) years enrolled in retrospective analysis who were referred to surgical intervention due to left main (51, 32%) and multivessel (108, 68%) disease. The regression analysis for long-term mortality risk and the Kaplan-Meyer survival curve were analyzed. Results: Multivariable analysis pointed female sex (HR = 1.08, 95% CI: 1.03-1.14, p = 0.001) and diabetes mellitus (HR = 6.33, 95% CI: 1.86-21.52, p = 0.003) as possible risk factors for 10-year mortality risk. There was no significant difference in Kaplan-Meyer 10-year mortality comparison between left main and multivessel disease patients treated by off-pump surgical revascularization (HR = 0.93, 95% CI: 0.40-2.13, p = 0.86). Conclusions: Off-pump surgery in the left main disease, compared to multivessel disease, represents a safe surgical technique with satisfactory long-term results. The female sex and diabetes mellitus were found as possible risk factors for 10-year mortality risk in multivariable analysis.

Incidence and predictors of device-related thrombus after left atrial appendage closure with Watchman device.

Introduction: Left atrial appendage closure (LAAC) with Watchman device prevents thromboembolism in patients with atrial fibrillation (AF). However, thrombus may develop on the atrial surface of the device. Aim: To investigate the incidence and predictors of device-related thrombus (DRT) in patients with AF who were treated with LAAC. Material and methods: Ninety-one consecutive patients with AF underwent LAAC procedure using first-generation Watchman 2.5 device followed by antiplatelet therapy. In our analysis we have included all patients (n = 78) who had clinical follow-up visits with transesophageal echocardiography (TEE) after the procedure. Results: The median (IQR) CHA2DS2-VASc score was 4 (4.0-6.0) and HAS-BLED score was 3 (3.0-4.0). DRTs were observed in 5 (6.4%) patients. When compared with patients without DRT, those with DRT presented more often with lower median ejection fraction (40% (23.5-45.5) versus 55% (48.0-60.0); p = 0.005), lower emptying velocity of LAA (25 cm/s (17.5-27.0) versus 53 cm/s (26.5-78.0); p = 0.009), and with greater depth of implantation (18 mm (14.0-20.5) versus 8 mm (5.0-11.0); p < 0.001). Furthermore, patients with DRT had greater depth of LAA (35 mm (29.5-41.0) versus 29 mm (25.5-31.0); p = 0.003), greater mean (SD) dimension in 900 (22.4 mm (3.2) versus 19 mm (2.7); p = 0.02). Patients with DRT were also younger than those without DRT (67.4 years (7) versus 75 years (8.3), p = 0.045). Conclusions: The DRT after Watchman device implantation remains a rare complication. Its formation was related to several patient and procedural characteristics, which need to be confirmed in larger studies.

Clopidogrel resistance and its relevance: Current concepts.

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

Epidemiology of maxillofacial trauma in elderly patients receiving oral anticoagulant or antithrombotic medication; a Swiss retrospective study.

BACKGROUND: The percentage of elderly trauma patients under anticoagulation and antiplatelet agents has been rising lately. As newer agents are introduced, each comes with its own advantages and precautions. Our study covered elderly patients admitted to the ED with maxillofacial trauma while on anticoagulation (AC) or antiplatelet therapy (APT). We aimed to investigate the demographic characteristics, causes, and types of maxillofacial trauma, along with concomitant injuries, duration of hospitalisation, haemorrhagic complications, and the overall costs of care in the emergency department (ED). METHODS: Data were gathered from the ED of Bern University Hospital. In this retrospective analysis, patients over 65 of age were included, who presented at our ED with maxillofacial trauma between 2013 and 2019 while undergoing treatment with therapeutic AC/APT. RESULTS: The study involved 188 patients with a median age of 81 years (IQR: 81 [74; 87]), of whom 55.3% (n=104) were male. More than half (54.8%, n=103) were aged 80 years or older. Cardiovascular diseases were present in 69.7% (n=131) of the patients, with the most common indications for AC/APT use being previous thromboembolic events (41.5%, n=78) and atrial fibrillation (25.5%, n=48). The predominant cause of facial injury was falls, accounting for 83.5% (n=157) of cases, followed by bicycle accidents (6.9%, n=13) and road-traffic accidents (5.3%, n=10). The most common primary injuries were fractures of the orbital floor and/or medial/lateral wall (60.1%, n=113), zygomatic bone (30.3%, n=57), followed by isolated orbital floor fractures (23.4%, n=44) and nasal bone fractures (19.1%, n=36). Fractures of the mandible occurred in 14.9% (n=28). Facial hematomas occurred in 68.6% of patients (129 cases), primarily in the midface area. Relevant facial bleeding complications were intracerebral haemorrhage being the most frequent (28.2%, n=53), followed by epistaxis (12.2%, n=23) and retrobulbar/intraorbital hematoma (9%, n=17). Sixteen patients (8.5%) experienced heavy bleeding that required emergency treatment. The in-hospital mortality rate was 2.1% (4 cases). CONCLUSIONS: This study indicates that falls are the leading cause of maxillofacial trauma in the elderly, with the most common diagnoses being orbital, zygomatic, and nasal fractures. Haemorrhagic complications primarily involve facial hematomas, especially in the middle third of the face, with intracerebral haemorrhage being the second most frequent. Surgical intervention for bleeding was required in 8.5% of cases. Given the aging population, it is essential to improve prevention strategies and update safety protocols, particularly for patients on anticoagulant/antiplatelet therapy (AC/APT). This can ensure rapid diagnostic imaging and prompt treatment in emergencies.

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.

Early dual antiplatelet therapy in patients with minor ischemic stroke after intravenous thrombolysis.

OBJECTIVES: Minor stroke is defined by a score of 5 or less on the National Institutes of Health Stroke Scale (NIHSS). Prior trials have shown efficacy of short term dual antiplatelet therapy (DAPT) in secondary prevention of stroke among patients with transient ischemic attack (TIA) or minor ischemic stroke, but no randomized clinical trials have studied this benefit after intravenous thrombolysis (IVT). Our aim was to investigate the safety of DAPT within 90 days after IVT in patients with acute minor ischemic stroke. PATIENTS: and methods We reviewed medical records of patients older than 18 years that received IVT between January 2015 and December 2022. Patients had a diagnosis of acute minor stroke or averted stroke (complete recovery and negative image on follow-up). Single or dual antiplatelet treatment was started 24 hours after thrombolysis according to the physician's judgment. Patients were divided in two groups: single and dual antiplatelet therapy. We assessed clinical outcome using the modified Rankin scale (mRS), symptomatic intracranial hemorrhage (SICH) and mortality at 90 days. RESULTS: Fifty-three patients met the inclusion criteria, 68% men aged 64±16,5 years. Seventy five percent had an ischemic stroke and 25% had an averted stroke. Median door-to-needle time was 50 minutes. Fifty one percent were in the single antiplatelet group and 49% in the dual antiplatelet therapy group. There were no differences in demographic and clinical characteristics between groups. The 90-day mRS did not show significant difference between groups. No patients had SICH nor died during follow-up. One patient in the single antiplatelet group had stroke recurrence. CONCLUSIONS: Dual antiplatelet therapy after IVT with rt-PA for acute minor ischemic stroke appears not to increase the risk of bleeding and mortality compared to single antiplatelet therapy in the first three months after the event. This is the first study to assess this subject in a Latin American population.

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/.

Comparison Between Mono VS Dual VS Triple Antiplatelet Therapy In Patients With Ischemic Heart Disease Undergoing PCI, A Network Meta-Analysis.

AIMS: We aim to research the efficacy and safety of single(SAPT), dual(DAPT), and triple(TAPT) antiplatelets approaches across IHD patients undergoing PCI. METHODS AND RESULTS: A network meta-analysis was conducted until April 1st, 2024, using the netmeta package in R studio 4.3.3. Primary outcomes were cardiac death, myocardial infarction(MI), stent thrombosis, stroke, and major bleeding(BARC 3-5). From 25 studies, a total of 65115 patients were included. For cardiac death, TAPT had no different risk than DAPT compared to SAPT [RR = 0.74; 95%CI (0.40 to 1.35); p-value = 0.33], [RR = 1.01, 95%CI (0.84 to 1.19); p-value = 0.87] respectively. For MI, TAPT had no different risk than DAPT compared to SAPT [RR = 0.77; 95%CI (0.51 to 1.16); p-value = 0.2047], [RR = 0.81, 95%CI (0.64 to 1.03); p-value = 0.0850] respectively. For stent thrombosis, DAPT had no different risk than TAPT compared to SAPT [RR = 0.74; 95%CI (0.45 to 1.21); p-value = 0.2284], [RR = 0.84, 95%CI (0.27 to 2.59); p-value = 0.7630] respectively. For stroke, DAPT had no different risk than TAPT in comparison to SAPT [RR = 0.91; 95%CI (0.75 to 1.10); p-value = 0.3209], and [RR = 0.87, 95%CI (0.43 to 1.76); p-value=0.6937], respectively. For Major bleeding(BARC 3-5), DAPT and TAPT increased major bleeding compared to SAPT, with only DAPT showing statistical significance. [RR = 1.43; 95%CI (1.09 to 1.88); p-value = 0.0107], and [RR = 2.78, 95%CI (0.90 to 4.78); p-value = 0.0852], respectively. CONCLUSION: DAPT and TAPT increased the risk of bleeding events compared to SAPT. However, we found no significant differences between these regimens for the other primary outcomes.