ticagrelor and Thromboembolism

Antiplatelet therapy is extensively used in the primary and secondary prophylaxis of arterial thrombotic disorders. Aspirin, the most commonly used antiplatelet agent, is a cyclooxygenase-1 inhibitor and considered a mild to moderate inhibitor of platelet function. Therefore, often a second antiplatelet agent is necessary in certain clinical conditions requiring greater inhibition of platelet function. An adenosine diphosphate (ADP) receptor, P2Y12, is an important target for this purpose; several agents inhibit this receptor providing potent antiplatelet effect. One of the side effects of these agents is bleeding, which in some patients may require reversal of antiplatelet effect. Similarly, patients undergoing emergent surgeries may benefit from reversal of antiplatelet effect to avoid excessive surgical bleeding. This article reviews current literature on this topic.

Topics: Aspirin; Blood Loss, Surgical; Blood Platelets; Cyclooxygenase Inhibitors; Hemorrhage; Hemostasis; Humans; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thromboembolism; Ticagrelor

Antithrombotic agents are the cornerstones of therapy for thrombosis. The compositions of arterial and venous clots differ, rendering antiplatelet agents more effective for arterial thrombosis and anticoagulants more effective for venous disease. Despite taking acetylsalicylic acid, some patients with arterial disease experience thrombotic events. The addition of the ADP-receptor antagonist clopidogrel to therapeutic regimens containing acetylsalicylic acid improves outcomes in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. However, clopidogrel has several limitations, including variable absorption, drug-drug interactions and genetic factors that lead to reduced generation of the active metabolite, and a delayed onset and offset of action. A search for new ADP-receptor inhibitors has yielded drugs such as prasugrel, ticagrelor, and cangrelor. For patients with venous thrombosis, the coumarins have been the only available oral anticoagulants for more than 60 years. Despite their effectiveness in preventing and treating thromboembolism, coumarins have well-documented limitations, including drug-drug and drug-dietary interactions, a narrow therapeutic range, and inconvenience and cost of monitoring therapy. A search for new oral anticoagulants has yielded drugs such as dabigatran etexilate, rivaroxaban, and apixaban. In this article, we review these new antithrombotic agents and provide plausible explanations for the results of phase III randomized controlled trials of these drugs.

Topics: Adenosine; Anticoagulants; Aspirin; Clopidogrel; Coronary Thrombosis; Coumarins; Fibrinolytic Agents; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Thromboembolism; Ticagrelor; Ticlopidine

The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear.. The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk.. Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT02164864.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; Stents; Thromboembolism; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA. The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA. Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA. Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Equivalence Trials as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Risk Assessment; Stroke; Thromboembolism; Ticagrelor; Warfarin

Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter.. We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813).. First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Topics: Aspirin; Clopidogrel; Hemorrhage; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy is widely used for stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) to prevent thromboembolic events (TEs). Compared to clopidogrel associated with aspirin, knowledge of the safety and efficacy of ticagrelor is lacking in large studies to date.. A retrospective cohort study was conducted from January 2016 to December 2018 with at least one year of follow-up in a single institution and systemic review.. Altogether, 153 patients with UIA receiving SACE were separated into two groups: 113 patients receiving clopidogrel plus aspirin and 40 patients receiving ticagrelor plus aspirin. Acute in-stent thrombotic events were noted in two patients in the clopidogrel group (1.77%) and none in the ticagrelor group (0%). Additionally, one patient (0.88%) in the clopidogrel group had an early ischemic stroke (<3 months). Delayed ischemic stroke was noted in 6 patients (5.31%) in the clopidogrel group and 3 patients (7.50%) in the ticagrelor group. There were no major hemorrhagic events in either group. The two groups showed no significant differences with regard to ischemic stroke or hemorrhagic stroke.. Compared to the clopidogrel based regimen, ticagrelor can also reduce TEs without increasing bleeding tendency for SACE of UIAs. Ticagrelor combined with low-dose aspirin is a safe and effective alternative option for SACE.

Topics: Aspirin; Clopidogrel; Embolization, Therapeutic; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Thromboembolism; Ticagrelor; Treatment Outcome

The current article describes a 72-year-old woman who suffered an acute myocardial infarction due to plaque erosion (PE) 2 weeks after abemaciclib treatment onset due to advanced breast cancer. Abemaciclib is a cyclin-dependent kinase 4 and 6 inhibitor that has recently demonstrated efficacy and safety in advanced breast cancer. Of major concern, however, reported thromboembolic rates in randomized clinical trials testing this drug range from 0.6 to 5%. To the best of our knowledge this is the first thrombotic coronary side effect ever reported. We suggest that a treatment that increases thromboembolic risk, such abemaciclib, may have triggered PE in our patient, 15 days after abemaciclib initiation. New molecules are promising in cancer treatment; however, care must be paid to their potential cardiotoxic effects.

Topics: Aged; Aminopyridines; Antineoplastic Agents; Artifacts; Benzimidazoles; Breast Neoplasms; Coronary Vessels; Enoxaparin; Female; Humans; Lipids; Myocardial Infarction; Protein Kinase Inhibitors; Thromboembolism; Ticagrelor; Treatment Outcome

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Thromboembolism; Ticagrelor; Treatment Outcome; Warfarin

Flow diversion (FD) is a common treatment modality for complex intracranial aneurysms. A major concern regarding the use of FD is thromboembolic events (TEE). There is debate surrounding the optimal antiplatelet regimen to prevent TEE. We aim to evaluate the safety and efficacy of ticagrelor as a single antiplatelet therapy (SAPT) for the prevention of TEE following FD for complex aneurysm treatment.. A retrospective review of a prospectively maintained neuroendovascular database at three endovascular centers was performed. Patients were included if they had an intracranial aneurysm that was treated with FD between January 2018 and September 2019 and were treated with ticagrelor as SAPT. Primary outcomes included early (within 72 hours post-procedure) and late (within 6 months) ischemic events.. A total of 24 patients (mean age 47.7 years) with 36 aneurysms were eligible for analysis, including 15 (62.5%) females. 14 (58.3%) patients presented with subarachnoid hemorrhage. 35 aneurysms arose from the anterior circulation and 1 from the posterior circulation. 23 aneurysms had a saccular morphology, whereas 7 were fusiform and 6 were blister. For the treatment of all 36 aneurysms, 30 procedures were performed with 32 FD devices. Procedural in-stent thrombosis occurred in 2 cases and was treated with intra-arterial tirofiban without complications. Aneurysm re-bleeding was reported in 1 (4.2%) patient. There were no reported early or late TEE. Three patients discontinued ticagrelor due to systemic side effects.. Ticagrelor is a safe and effective SAPT for the prevention of TEE after FD. Large multicenter prospective studies are warranted to validate our findings.

Topics: Adult; Aged; Embolization, Therapeutic; Female; Follow-Up Studies; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome

Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y. To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .. Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).. We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients.. In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome; United States

To reduce procedural thromboembolisms, tailored antiplatelet drug preparation has been used according to antiplatelet resistance for endovascular coiling of unruptured aneurysms. We compared an aspirin plus clopidogrel group with a ticagrelor group using diffusion-weighted imaging (DWI) after stent-assisted coiling for unruptured aneurysms.. From October 2018 to April 2019, 72 patients with 78 aneurysms underwent stent-assisted coiling, with aspirin plus clopidogrel (n = 20 patients with 22 aneurysms) or ticagrelor (n = 52 patients with 56 aneurysms) as an antiplatelet preparation, and were enrolled in our study. All patients were evaluated using DWI 2 h after coiling to detect procedural thromboembolisms.. Postprocedure infarction was observed on DWI in 37 procedures (47.4%), and symptomatic infarction occurred in 1 procedure (1.28%). Postprocedure infarction was significantly lower in the aspirin plus clopidogrel than in ticagrelor group (27.3% vs. 55.4%, p = 0.043). Postprocedure infarction was associated with aneurysm type (sidewall aneurysm (30.8%) vs. aneurysm with incorporated branches (64.1%), p = 0.006) and guiding catheter type (single (23.8%) vs. double (56.1%), p = 0.020). Multivariable logistic regression analysis demonstrated that postprocedure infarction was related to aneurysm type (adjusted odds ratio (OR); 3.317, confidence interval (CI); 1.223-8.991, p = 0.018), guiding catheter type (adjusted OR; 2.783, CI; 0.828-9.353, p = 0.098), and antiplatelet medication (adjusted OR; 1.295, CI; 0.969-1.730, p = 0.080).. Postprocedure infarction was observed on DWI after stent-assisted coiling for unruptured aneurysms more frequently in the ticagrelor group than in the aspirin plus clopidogrel group. However, our study suggests that postprocedure infarction is more associated with aneurysm type than antiplatelet medication.

Topics: Adult; Aged; Aspirin; Clopidogrel; Diffusion Magnetic Resonance Imaging; Embolization, Therapeutic; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Platelet Aggregation Inhibitors; Stents; Thromboembolism; Ticagrelor

Although the new oral P2Y12 inhibitors, prasugrel/ticagrelor have shown greater efficacy than clopidogrel in patients with the acute coronary syndrome, but they have not shown better efficacy in Korean patients. So we evaluated the efficacy of the prasugrel/ticagrelor in patients with myocardial infarction (MI) and diabetes, a more high-risk patients group.From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 3985 patients with MI and diabetes who underwent PCI were enrolled between November 2011 and December 2015. The patients were divided into 2 groups: clopidogrel (n = 2985) and prasugrel/ticagrelor (n = 1000).After propensity score matching, prasugrel/ticagrelor group showed a no significant difference in risk of the composite of cardiac death (CD), recurrent MI or stroke (hazard ratio [HR], 0.705; 95% confidence interval [CI], 0.474-1.048; P = .084). However, the risk of major bleeding was significantly higher in the prasugrel/ticagrelor group. (HR; 2.114, 95% CI; [1.027-4.353], P = .042). In subgroup analysis, major bleeding was significantly increased in the subgroup of creatinine clearance <60 ml/min/1.73 m, hypertension, underwent a trans-femoral approach and diagnosed as NSTEMI among the prasugrel/ticagrelor group.The use of prasugrel/ticagrelor did not improve the composite of CD, recurrent MI or stroke, however, significantly increased major bleeding events in Korean patients with MI and diabetes undergoing PCI.

Topics: Aged; Clopidogrel; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Period; Prasugrel Hydrochloride; Republic of Korea; Thromboembolism; Ticagrelor

The development of thromboembolism is one of the most common complications of neuroendovascular procedures. Although several small studies have deemed clopidogrel safe and effective in the prevention of intracranial stent thrombosis, ticagrelor has yet to be assessed in this setting.. The objective of this study was to retrospectively evaluate the safety and efficacy of ticagrelor in patients undergoing neuroendovascular procedures.. A retrospective review of patients receiving ticagrelor following neuroendovascular aneurysm repair.. A total of 5 patients undergoing neuroendovascular aneurysm repair received ticagrelor for a median of 5 days while hospitalized. Three patients were treated with stent-assisted coiling, while 2 received pipeline embolization devices. All patients received additional low-dose aspirin therapy. One patient received ticagrelor after experiencing a thrombotic event on clopidogrel, while a second patient was treated with ticagrelor after developing a dermatologic reaction to clopidogrel. Three (60%) patients were successfully treated and discharged on ticagrelor therapy. Two patients experienced cerebrovascular accidents following aneurysm repair while receiving ticagrelor, one of which was potentially due to medication omission. One (20%) patient receiving ticagrelor experienced a small retroperitoneal hematoma; however, ticagrelor therapy was continued without further complication.. Therapy with ticagrelor may be a safe and effective treatment option for patients undergoing neuroendovascular aneurysm repair. However, future studies are warranted to substantiate these findings.

Topics: Adenosine; Adult; Aged; Endovascular Procedures; Female; Humans; Male; Middle Aged; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Thromboembolism; Ticagrelor; Treatment Outcome

Ticagrelor was daily administered throughout pregnancy to a 37-year-old pregnant woman until 36 weeks of gestation. The patient, with Behçet disease, suffered from a non-ST elevation myocardial infarction 4 months before conception, possibly related to hypertension and tobacco abuse. Pregnancy and postpartum periods were uneventful. She delivered a healthy but small-for-gestational-age term neonate.

Topics: Adenosine; Adult; Aspirin; Drug Therapy, Combination; Female; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Thromboembolism; Ticagrelor

Topics: Adenosine; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cardiovascular Diseases; Clopidogrel; Dabigatran; Fibrinolytic Agents; Guideline Adherence; Humans; Morpholines; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Ticagrelor; Ticlopidine; Treatment Outcome