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1.
Neurosurg Rev ; 47(1): 258, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38839660

ABSTRACT

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.


Subject(s)
Aspirin , Cerebral Hemorrhage , Platelet Aggregation Inhibitors , Humans , Male , Female , Aspirin/adverse effects , Aspirin/administration & dosage , Aged , Middle Aged , Retrospective Studies , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Postoperative Hemorrhage/epidemiology , Risk Factors , Adult , Intracranial Hemorrhages/epidemiology
2.
Ugeskr Laeger ; 186(18)2024 Apr 29.
Article in Danish | MEDLINE | ID: mdl-38704715

ABSTRACT

Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended prophylactic low-dose acetylsalicylic acid (LDA). If new screening algorithms are implemented, LDA will be recommended to around 10% of pregnant women. The use of LDA may slightly increase the risk of minor bleeding disturbances. Otherwise, there is a lot of promising data regarding the safety of LDA use during pregnancy, as argued in this review.


Subject(s)
Aspirin , Pre-Eclampsia , Humans , Pre-Eclampsia/prevention & control , Pregnancy , Aspirin/administration & dosage , Aspirin/adverse effects , Aspirin/therapeutic use , Female , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects
3.
JACC Cardiovasc Interv ; 17(9): 1119-1130, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38749592

ABSTRACT

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).


Subject(s)
Aspirin , Coronary Artery Disease , Drug Administration Schedule , Drug-Eluting Stents , Dual Anti-Platelet Therapy , Everolimus , Hemorrhage , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Prasugrel Hydrochloride , Prosthesis Design , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Male , Time Factors , Female , Aspirin/administration & dosage , Aspirin/adverse effects , Aspirin/therapeutic use , Aged , Middle Aged , Treatment Outcome , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Risk Factors , Prasugrel Hydrochloride/administration & dosage , Prasugrel Hydrochloride/adverse effects , Prasugrel Hydrochloride/therapeutic use , Everolimus/administration & dosage , Everolimus/adverse effects , Coronary Artery Disease/therapy , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Thrombosis/etiology , Coronary Thrombosis/prevention & control , Acute Coronary Syndrome/therapy , Acute Coronary Syndrome/diagnostic imaging , Chromium Alloys , Risk Assessment , Drug Therapy, Combination
4.
Trials ; 25(1): 324, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755709

ABSTRACT

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.


Subject(s)
Aortic Valve , Aspirin , Bioprosthesis , Factor Xa Inhibitors , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Pyrazoles , Pyridones , Randomized Controlled Trials as Topic , Thrombosis , Humans , Aspirin/administration & dosage , Aspirin/therapeutic use , Aspirin/adverse effects , Pyridones/therapeutic use , Pyridones/administration & dosage , Pyridones/adverse effects , Prospective Studies , Heart Valve Prosthesis/adverse effects , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Thrombosis/prevention & control , Thrombosis/etiology , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Treatment Outcome , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Female , Male , Middle Aged , Time Factors , Aged , Adult , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects
5.
Neurology ; 102(12): e209442, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38771998

ABSTRACT

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.


Subject(s)
Cerebral Hemorrhage , Fibrinolytic Agents , Registries , Humans , Male , Female , Aged , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/chemically induced , Denmark/epidemiology , Middle Aged , Fibrinolytic Agents/adverse effects , Aged, 80 and over , Platelet Aggregation Inhibitors/adverse effects , Anticoagulants/adverse effects , Clopidogrel/adverse effects , Clopidogrel/therapeutic use , Aspirin/adverse effects , Incidence
7.
BMC Gastroenterol ; 24(1): 187, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811868

ABSTRACT

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.


Subject(s)
Aspirin , Gastric Mucosa , Gastrins , Omeprazole , Proton Pump Inhibitors , Rats, Sprague-Dawley , Animals , Aspirin/adverse effects , Aspirin/administration & dosage , Omeprazole/pharmacology , Omeprazole/administration & dosage , Proton Pump Inhibitors/pharmacology , Proton Pump Inhibitors/administration & dosage , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gastrins/blood , Male , Rats , Drug Administration Schedule , Humans , Peptic Ulcer/prevention & control , Peptic Ulcer/chemically induced , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Stomach Ulcer/prevention & control , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology
9.
Sr Care Pharm ; 39(6): 218-227, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38803024

ABSTRACT

Background National guidelines no longer recommend adults 60 years of age and older to begin treatment with low-dose daily aspirin for primary prevention of atherosclerotic cardiovascular disease (CVD) due to a lack of proven net benefit and a higher risk of bleeding. Objective The objective of this cross-sectional retrospective analysis was to evaluate the appropriateness of low-dose aspirin prescribing and subsequent gastrointestinal bleeding in older persons receiving primary care in a large academic health system. Setting Large, academic health system within Colorado. Patients Patients with an active order for daily low-dose aspirin as of July 1, 2021, were assessed for appropriateness based on indication (primary vs secondary prevention) and use of a concomitant proton-pump inhibitor (PPI). Incident gastrointestinal bleeds (GIBs) in the subsequent 12 months and GIB risk factors were also evaluated. Results A total of 19,525 patients were included in the analysis. Eighty-nine percent of patients identified as White and 54% identified as male. Of the total cohort, 44% had CVD and 19% were co-prescribed a PPI. GIB occurred in 247 patients (1.27%) within the subsequent year. Risk factors significantly associated with a GIB within 1 year included: history of GIB, history of peptic ulcer disease, other esophageal issue (esophagitis, Barrett's esophagus, Mallory Weiss tears, etc.), 75 years of age or older, and history of gastroesophageal reflux disease. Conclusion This evaluation found that many older persons at this institution may be inappropriately prescribed aspirin, providing opportunities for pharmacists to improve medication safety by deprescribing aspirin among primary prevention patients or potentially co-prescribing a PPI in secondary prevention patients.


Subject(s)
Aspirin , Gastrointestinal Hemorrhage , Humans , Aspirin/adverse effects , Aspirin/therapeutic use , Aspirin/administration & dosage , Male , Gastrointestinal Hemorrhage/prevention & control , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Female , Aged , Retrospective Studies , Middle Aged , Cross-Sectional Studies , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Aged, 80 and over , Colorado/epidemiology , Primary Health Care , Risk Factors , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Primary Prevention , Academic Medical Centers , Secondary Prevention/methods , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy
10.
Sci Rep ; 14(1): 12507, 2024 05 31.
Article in English | MEDLINE | ID: mdl-38822153

ABSTRACT

Aspirin is widely used for both primary and secondary prevention of panvascular diseases, such as stroke and coronary heart disease (CHD). The optimal balance between reducing panvascular disease events and the potential increase in bleeding risk remains unclear. This study aimed to develop a predictive model specifically designed to assess bleeding risk in individuals using aspirin. A total of 58,415 individuals treated with aspirin were included in this study. Detailed data regarding patient demographics, clinical characteristics, comorbidities, medical history, and laboratory test results were collected from the Affiliated Dongyang Hospital of Wenzhou Medical University. The patients were randomly divided into two groups at a ratio of 7:3. The larger group was used for model development, while the smaller group was used for internal validation. To develop the prediction model, we employed least absolute shrinkage and selection operator (LASSO) regression followed by multivariate logistic regression. The performance of the model was assessed through metrics such as the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). The LASSO-derived model employed in this study incorporated six variables, namely, sex, operation, previous bleeding, hemoglobin, platelet count, and cerebral infarction. It demonstrated excellent performance at predicting bleeding risk among aspirin users, with a high AUC of 0.866 (95% CI 0.857-0.874) in the training dataset and 0.861 (95% CI 0.848-0.875) in the test dataset. At a cutoff value of 0.047, the model achieved moderate sensitivity (83.0%) and specificity (73.9%). The calibration curve analysis revealed that the nomogram closely approximated the ideal curve, indicating good calibration. The DCA curve demonstrated a favorable clinical net benefit associated with the nomogram model. Our developed LASSO-derived predictive model has potential as an alternative tool for predicting bleeding in clinical settings.


Subject(s)
Aspirin , Hemorrhage , Humans , Aspirin/adverse effects , Male , Female , Hemorrhage/chemically induced , Middle Aged , Aged , ROC Curve , Risk Assessment/methods , Risk Factors , Logistic Models , Platelet Aggregation Inhibitors/adverse effects
11.
J Am Heart Assoc ; 13(11): e032778, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38690705

ABSTRACT

BACKGROUND: Aspirin, an effective, low-cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self-administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use. METHODS AND RESULTS: We developed a population simulation model to determine the impact of self-administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643-14 574) deaths annually, after accounting for deaths due to bleeding (963; 926-1003). This translated to an estimated 166 309 YOLS (149391-185 505) at the cost of $643 235 (633 944-653 010) per year, leading to a cost-effectiveness ratio of $3.70 (3.32-4.12) per YOLS. CONCLUSIONS: For <$4 per YOLS, self-administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post-AMI outweighed the risk of bleeding deaths from aspirin 10 times over.


Subject(s)
Aspirin , Chest Pain , Platelet Aggregation Inhibitors , Humans , Aspirin/administration & dosage , Aspirin/adverse effects , United States/epidemiology , Male , Female , Middle Aged , Chest Pain/diagnosis , Chest Pain/mortality , Adult , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Self Administration , Hemorrhage/chemically induced , Hemorrhage/mortality , Hemorrhage/epidemiology , Aged , Cost-Benefit Analysis , Mortality, Premature , Myocardial Infarction/mortality , Myocardial Infarction/diagnosis , Time Factors
12.
J Am Heart Assoc ; 13(11): e033985, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38804212

ABSTRACT

BACKGROUND: ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y12 receptors inhibits platelet aggregation and represents an effective cardiovascular disease prevention strategy. AZD3366 (APT102), a long-acting recombinant form of an optimized CD39L3 human apyrase, has effectively reduced ATP, ADP, and platelet aggregation and provided tissue protection in preclinical models, features that could be very beneficial in treating patients with cardiovascular disease. METHODS AND RESULTS: We conducted this phase 1, first-in-human study of single ascending doses of intravenous AZD3366 or placebo, including doses added to dual antiplatelet therapy with ticagrelor and acetylsalicylic acid. The primary objective was safety and tolerability; secondary and exploratory objectives included pharmacokinetics, pharmacodynamics (measured as inhibition of platelet aggregation), adenosine diphosphatase (ADPase) activity, and ATP/ADP metabolism. In total, 104 participants were randomized. AZD3366 was generally well tolerated, with no major safety concerns observed. ADPase activity increased in a dose-dependent manner with a strong correlation to AZD3366 exposure. Inhibition of ADP-stimulated platelet aggregation was immediate, substantial, and durable. In addition, there was a prompt decrease in systemic ATP concentration and an increase in adenosine monophosphate concentrations, whereas ADP concentration appeared generally unaltered. At higher doses, there was a prolongation of capillary bleeding time without detectable changes in the ex vivo thromboelastometric parameters. CONCLUSIONS: AZD3366 was well tolerated in healthy participants and demonstrated substantial and durable inhibition of platelet aggregation after single dosing. Higher doses prolonged capillary bleeding time without detectable changes in ex vivo thromboelastometric parameters. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04588727.


Subject(s)
Apyrase , Aspirin , Platelet Aggregation Inhibitors , Platelet Aggregation , Ticagrelor , Humans , Male , Ticagrelor/pharmacokinetics , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Female , Apyrase/metabolism , Apyrase/administration & dosage , Platelet Aggregation/drug effects , Aspirin/administration & dosage , Aspirin/pharmacokinetics , Aspirin/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Middle Aged , Adult , Double-Blind Method , Dual Anti-Platelet Therapy , Drug Therapy, Combination , Young Adult , Adenosine Diphosphate , Blood Platelets/drug effects , Blood Platelets/metabolism , Dose-Response Relationship, Drug , Treatment Outcome , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacokinetics , Purinergic P2Y Receptor Antagonists/pharmacokinetics , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/pharmacology
13.
BMC Med ; 22(1): 148, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38561738

ABSTRACT

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.


Subject(s)
Acute Coronary Syndrome , Isoindoles , Percutaneous Coronary Intervention , Phenylbutyrates , Humans , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/surgery , Aspirin/adverse effects , Drug Therapy, Combination , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/adverse effects , Registries , Treatment Outcome
16.
J Am Heart Assoc ; 13(8): e032782, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38563380

ABSTRACT

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.


Subject(s)
Myocardial Infarction , Peripheral Arterial Disease , Humans , Aspirin/adverse effects , Drug Therapy, Combination , Factor Xa Inhibitors/adverse effects , Hemorrhage/chemically induced , Myocardial Infarction/drug therapy , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/surgery , Platelet Aggregation Inhibitors/adverse effects , Risk Assessment , Rivaroxaban/adverse effects
17.
Clin Appl Thromb Hemost ; 30: 10760296241244772, 2024.
Article in English | MEDLINE | ID: mdl-38571479

ABSTRACT

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a standard therapy in patients with ischemic vascular diseases (IVD) including coronary artery, cerebrovascular and peripheral arterial diseases, although the optimal duration of this treatment is still debated. Previous meta-analyses reported conflicting results about the effects of long-term and short-term as well as non-DAPT use in various clinical settings. Herein, we conducted a comprehensive meta-analysis to assess the efficacy and safety of different durations of DAPT. METHODS: We reviewed relevant articles and references from database, which were published prior to April 2023. Data from prospective studies were processed using RevMan5.0 software, provided by Cochrane Collaboration and transformed using relevant formulas. The inclusion criteria involved randomization to long-term versus short-term or no DAPT; the endpoints included at least one of total or cardiovascular (CV) mortalities, IVD recurrence, and bleeding. RESULTS: A total of 34 randomized studies involving 141 455 patients were finally included. In comparison with no or short-term DAPT, long-term DAPT reduced MI and stroke, but did not reduce the total and CV mortalities. Meanwhile, bleeding events were increased, even though intracranial and fatal bleedings were not affected. Besides, the reduction of MI and stroke recurrence showed no statistical significance between long-term and short-term DAPT groups. CONCLUSION: Long-term DAPT may not reduce the mortality of IVD besides increasing bleeding events, although reduced the incidences of MI and stroke early recurrence to a certain extent and did not increase the risk of fatal intracranial bleeding.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Humans , Aspirin/adverse effects , Drug Therapy, Combination , Hemorrhage/etiology , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Randomized Controlled Trials as Topic , Stroke/etiology , Treatment Outcome
18.
Can J Urol ; 31(2): 11834-11839, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38642461

ABSTRACT

INTRODUCTION: Studies have reached mixed conclusions on the role of antiplatelet and anticoagulant agents on postoperative complications of partial nephrectomies. This study examines whether preoperative anticoagulation use affected the risk of hemorrhagic complications after partial nephrectomy. MATERIALS AND METHODS: This is a retrospective chart review of all partial nephrectomies performed between 2017 and 2022 at a single institution. For each operation, preoperative data was gathered on whether the patient was on anticoagulation, the type and dose of anticoagulation, and how many days the anticoagulation was held preoperatively. Bivariate analyses for continuous measures were performed using Student's t-tests when there were two comparison groups and ANOVA models when there were more than two comparison groups and Chi-Square tests were used for categorical variables, with Fisher's Exact being used when expected cell counts were small. RESULTS: In this study, warfarin was held for an average of 5.43 days, clopidogrel was held for an average of 6.60 days, aspirin was held for an average of 7.65 days, and direct oral anticoagulants (DOACs) were held for an average of 4.00 days. There was no significant difference in hemoglobin (Hb) change, rate of intraoperative transfusion, postoperative transfusion, bleeding complication, pseudoaneurysm rate, or additional bleeding processes between patients on prior anticoagulation therapy and those not on therapy. There was no significant difference in intraoperative or postoperative outcomes based on history of aspirin use and continuation of aspirin through the surgery. While estimated blood loss appeared statistically significant initially, this difference was accounted for by the covariates of comorbidities, RENAL score, surgical approach, and type of renorrhaphy. Overall, there was no difference in complication rate based solely on aspirin use or continuation of aspirin through surgery. CONCLUSIONS: No difference in complication rate of partial nephrectomy was determined to be solely due to prior use of anticoagulation or aspirin use alone with appropriate cessation of anticoagulation preoperatively. Overall, patients on anticoagulation are not at a higher risk of intraoperative or postoperative bleeding complications when undergoing partial nephrectomy.


Subject(s)
Anticoagulants , Aspirin , Humans , Aspirin/adverse effects , Anticoagulants/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Nephrectomy/adverse effects
20.
J Robot Surg ; 18(1): 181, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662167

ABSTRACT

To evaluate the safety and feasibility of continued perioperative aspirin at the time of robotic assisted simple prostatectomy (RASP). We performed a retrospective review of our IRB approved institutional database of patients who underwent RASP between 2013 and 2022. Comparative groups included patients taking aspirin in the perioperative period and those not taking aspirin pre-operatively. The primary outcome was any post-operative bleeding related complication using the modified Clavien-Dindo classification. Secondary outcomes included the identification of risk factors for increased blood loss in the entire study population, operative time, and blood transfusion requirement. 143 patients underwent RASP of which 55 (38.5%) patients continued perioperative aspirin therapy and 88 (61.5%) patients did not. Baseline demographics were similar between groups. Patients taking perioperative aspirin had a higher rate of hypertension (74.5% vs 58.0%, p = 0.04) and other cardiovascular disease (30.9% vs 11.4%, p = 0.007). Postoperative complications were similar between the groups (Clavien-Dindo ≥ 3; p = 0.43). Median blood loss (150 cc vs 150 cc, p = 0.38), percentage drop in hemoglobin (13.4 vs 13.2, p = 0.94) and blood transfusion rate (3.6 vs 1.1, p = 0.56) were also similar between groups. The median blood loss was 150 ml for the whole study population. On regression analysis, neither aspirin nor any other variable was associated with increased blood loss (> 150 ml). Aspirin can be safely continued perioperatively in patients undergoing RASP without any risk of bleeding related complications, blood loss, or increased transfusion rate.


Subject(s)
Aspirin , Laparoscopy , Prostatectomy , Robotic Surgical Procedures , Humans , Prostatectomy/methods , Prostatectomy/adverse effects , Aspirin/administration & dosage , Aspirin/adverse effects , Aspirin/therapeutic use , Male , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Middle Aged , Retrospective Studies , Aged , Laparoscopy/methods , Laparoscopy/adverse effects , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/prevention & control , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Blood Transfusion/statistics & numerical data , Blood Loss, Surgical/statistics & numerical data , Operative Time , Risk Factors , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome
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