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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.
Drug Des Devel Ther ; 18: 1811-1819, 2024.
Article in English | MEDLINE | ID: mdl-38828024

ABSTRACT

Purpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators. Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis. Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted-P =3.55*10-209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI. Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.


Subject(s)
Acute Coronary Syndrome , Morphine , Purinergic P2Y Receptor Antagonists , Humans , Morphine/adverse effects , Morphine/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Acute Coronary Syndrome/drug therapy , Male , Female , Middle Aged , Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Analgesics, Opioid/adverse effects , Analgesics, Opioid/administration & dosage
4.
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
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
6.
Pharmacoepidemiol Drug Saf ; 33(6): e5816, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773801

ABSTRACT

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.


Subject(s)
Clopidogrel , Gastrointestinal Hemorrhage , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Proton Pump Inhibitors , Humans , Clopidogrel/administration & dosage , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Male , Female , Aged , Middle Aged , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/prevention & control , Dual Anti-Platelet Therapy/methods , Esomeprazole/administration & dosage , Esomeprazole/therapeutic use , Omeprazole/administration & dosage , Omeprazole/therapeutic use , Omeprazole/adverse effects , Drug Interactions , Drug Therapy, Combination , Histamine H2 Antagonists/administration & dosage , Histamine H2 Antagonists/therapeutic use
7.
J Am Heart Assoc ; 13(10): e032390, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38742535

ABSTRACT

BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.


Subject(s)
Fatty Acids, Omega-3 , Hemorrhage , Randomized Controlled Trials as Topic , Humans , Fatty Acids, Omega-3/adverse effects , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Risk Assessment , Risk Factors , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage
8.
J Am Heart Assoc ; 13(10): e032248, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38761068

ABSTRACT

BACKGROUND: Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. METHODS AND RESULTS: The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes. CONCLUSIONS: In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. REGISTRATION: URL: https://clinicaltrials.gov. Identifier: NCT04734028.


Subject(s)
Clopidogrel , Cytochrome P-450 CYP2C19 , Genotype , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Percutaneous Coronary Intervention/adverse effects , Male , Female , Aged , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Republic of Korea/epidemiology , Clopidogrel/pharmacokinetics , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Aged, 80 and over , Prognosis , Treatment Outcome , Time Factors , Coronary Artery Disease/genetics , Coronary Artery Disease/surgery , Coronary Artery Disease/mortality , Coronary Artery Disease/therapy , Risk Factors , Dual Anti-Platelet Therapy/adverse effects , Risk Assessment , Age Factors , Myocardial Infarction/genetics , Myocardial Infarction/epidemiology , Pharmacogenomic Variants
10.
J Am Heart Assoc ; 13(10): e034716, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38726922

ABSTRACT

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.


Subject(s)
Anticoagulants , Cerebral Hemorrhage , Fibrinolytic Agents , Registries , Humans , Male , Female , Sweden/epidemiology , Aged , Retrospective Studies , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/epidemiology , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/adverse effects , Aged, 80 and over , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Treatment Outcome , Stroke/mortality , Stroke/epidemiology , Stroke/drug therapy , Vitamin K/antagonists & inhibitors , Administration, Oral , Activities of Daily Living , Risk Factors , Risk Assessment/methods
11.
J Am Heart Assoc ; 13(10): e033611, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38761083

ABSTRACT

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.


Subject(s)
Aspirin , Clopidogrel , Dual Anti-Platelet Therapy , Ischemic Stroke , Platelet Aggregation Inhibitors , Registries , Humans , Clopidogrel/therapeutic use , Aspirin/therapeutic use , Male , Aged , Female , Ischemic Stroke/drug therapy , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Ischemic Stroke/prevention & control , Dual Anti-Platelet Therapy/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Middle Aged , Treatment Outcome , Aged, 80 and over , Time Factors , Japan/epidemiology , Secondary Prevention/methods , Secondary Prevention/trends , Drug Therapy, Combination , Risk Factors
12.
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
14.
EuroIntervention ; 20(10): e630-e642, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38776146

ABSTRACT

BACKGROUND: A short dual antiplatelet therapy (DAPT) duration has been proposed for patients at high bleeding risk (HBR) undergoing drug-eluting coronary stent (DES) implantation. Whether this strategy is safe and effective after a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains uncertain. AIMS: We aimed to compare the impact of 1-month versus 3-month DAPT on clinical outcomes after DES implantation among HBR patients with or without NSTE-ACS. METHODS: This is a prespecified analysis from the XIENCE Short DAPT programme involving three prospective, international, single-arm studies evaluating the safety and efficacy of 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT among HBR patients after implantation of a cobalt-chromium everolimus-eluting stent. Ischaemic and bleeding outcomes associated with 1- versus 3-month DAPT were assessed according to clinical presentation using propensity score stratification. RESULTS: Of 3,364 HBR patients (1,392 on 1-month DAPT and 1,972 on 3-month DAPT), 1,164 (34.6%) underwent DES implantation for NSTE-ACS. At 12 months, the risk of the primary endpoint of death or myocardial infarction was similar between 1- and 3-month DAPT in patients with (hazard ratio [HR] 1.09, 95% confidence interval [CI]: 0.71-1.65) and without NSTE-ACS (HR 0.88, 95% CI: 0.63-1.23; p-interaction=0.34). The key secondary endpoint of Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding was consistently reduced in both NSTE-ACS (HR 0.57, 95% CI: 0.37-0.88) and stable patients (HR 0.84, 95% CI: 0.61-1.15; p-interaction=0.15) with 1-month DAPT. CONCLUSIONS: Among HBR patients undergoing implantation of an everolimus-eluting stent, 1-month, compared to 3-month DAPT, was associated with similar ischaemic risk and reduced bleeding at 1 year, irrespective of clinical presentation.


Subject(s)
Acute Coronary Syndrome , Drug-Eluting Stents , Dual Anti-Platelet Therapy , Hemorrhage , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/instrumentation , Acute Coronary Syndrome/therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Male , Middle Aged , Aged , Female , Hemorrhage/chemically induced , Treatment Outcome , Dual Anti-Platelet Therapy/methods , Prospective Studies , Time Factors , Risk Factors , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/mortality
15.
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
16.
J Am Heart Assoc ; 13(11): e031606, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38804216

ABSTRACT

Ticagrelor is a platelet P2Y12 receptor inhibitor approved for use in patients with acute coronary syndromes, coronary artery disease, and low-moderate risk acute ischemic stroke or high-risk transient ischemic attack. Clinical trials have evaluated the efficacy and safety of ticagrelor on ischemic and bleeding outcomes for different indications and with varying treatment approaches. As a result, there is a large body of clinical evidence demonstrating different degrees of net clinical benefit compared with other platelet inhibitor drugs based on indication, patient characteristics, clinical presentation, treatment duration, and other factors. We provide a review of the major trials of ticagrelor in the context of other randomized trials of clopidogrel and prasugrel to organize the volume of available information, elevate corroborating and conflicting data, and identify potential gaps as areas for further exploration of optimal antiplatelet treatment.


Subject(s)
Platelet Aggregation Inhibitors , Purinergic P2Y Receptor Antagonists , Ticagrelor , Humans , Ticagrelor/therapeutic use , Ticagrelor/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Acute Coronary Syndrome/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Coronary Artery Disease/drug therapy , Hemorrhage/chemically induced
17.
Cerebrovasc Dis Extra ; 14(1): 76-85, 2024.
Article in English | MEDLINE | ID: mdl-38697036

ABSTRACT

INTRODUCTION: Moyamoya disease (MMD) is an uncommon cause of stroke. Antiplatelet treatment is commonly prescribed for patients with MMD despite the lack of strong evidence supporting its efficacy. We conducted a systematic review to evaluate evidence of antiplatelet treatment and clinical outcomes among patients with MMD. METHODS: A systematic literature search was performed to identify studies that evaluated the association between antiplatelet treatment and clinical outcomes, including ischemic stroke, hemorrhagic stroke, functional outcome, survival, and bypass patency, in patients with MMD. The following databases were searched: PubMed, Embase, Scopus, and the Cochrane Library, from the inception date to February 2022. RESULTS: Eight studies were included in this systematic review. Six studies evaluated antiplatelet treatment and ischemic stroke. Most studies did not demonstrate a protective effect of antiplatelet treatment against ischemic stroke. Five studies evaluated antiplatelet treatment and hemorrhagic stroke. All of them did not demonstrate an increased risk of hemorrhagic stroke. One study found the benefit of antiplatelet treatment in terms of survival. Regarding the effect of antiplatelet treatment on functional outcome and patency of surgical bypass, the results were inconclusive. CONCLUSION: Current evidence suggests that antiplatelet treatment in patients with MMD did not demonstrate a protective effect against ischemic stroke. However, antiplatelet treatment did not increase the risk of hemorrhagic stroke in patients with MMD. The well-designed randomized controlled trial should be highlighted.


Subject(s)
Hemorrhagic Stroke , Ischemic Stroke , Moyamoya Disease , Platelet Aggregation Inhibitors , Humans , Moyamoya Disease/drug therapy , Moyamoya Disease/physiopathology , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome , Risk Factors , Hemorrhagic Stroke/prevention & control , Ischemic Stroke/prevention & control , Female , Risk Assessment , Male , Middle Aged , Adult , Young Adult , Adolescent , Aged , Child , Child, Preschool
18.
J Stroke Cerebrovasc Dis ; 33(7): 107760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38718871

ABSTRACT

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.


Subject(s)
Anticoagulants , Carotid Artery Thrombosis , Ischemic Attack, Transient , Ischemic Stroke , Platelet Aggregation Inhibitors , Humans , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Female , Retrospective Studies , Male , Aged , Middle Aged , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Treatment Outcome , Ischemic Stroke/drug therapy , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/diagnosis , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/diagnostic imaging , Ischemic Attack, Transient/etiology , Ischemic Attack, Transient/diagnosis , Carotid Artery Thrombosis/drug therapy , Carotid Artery Thrombosis/diagnostic imaging , Risk Factors , Time Factors , Recurrence , Dual Anti-Platelet Therapy
19.
Clin Appl Thromb Hemost ; 30: 10760296241254107, 2024.
Article in English | MEDLINE | ID: mdl-38780348

ABSTRACT

PURPOSE: Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. METHODS: We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. RESULTS: A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. CONCLUSION: The A4B score established in this study was better than the HAS-BLED score,and the same is true for the ABST score to the CHA2DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627).


Subject(s)
Hemorrhage , Ticagrelor , Humans , Ticagrelor/therapeutic use , Ticagrelor/adverse effects , Female , Male , Hemorrhage/chemically induced , Aged , Retrospective Studies , Middle Aged , Diabetes Mellitus/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Risk Factors , Ischemia/chemically induced , Thrombosis
20.
Brain Behav ; 14(5): e3540, 2024 May.
Article in English | MEDLINE | ID: mdl-38778788

ABSTRACT

INTRODUCTION: One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic antidiuretic hormone (ADH) analog. It has been linked to improving patient outcomes in antiplatelet-induced intracranial hemorrhage. The secondary outcomes included the incidence of thrombotic complications and neurological outcomes. METHODS: A systematic search was conducted on three databases (PubMed, Cochrane, and ClinicalTrials.gov) to find eligible literature that compares desmopressin (DDAVP) versus controls in patients with AA-ICH. The Mantel-Haenszel statistic was used to determine an overall effect estimate for each outcome by calculating the risk ratios and 95% confidence intervals (CI). Heterogeneity was measured using the I2 test. The risk of bias in studies was calculated using the New Castle Ottowa Scale. RESULTS: Five studies were included in the analysis with a total of 598 patients. DDAVP was associated with a nonsignificant decrease in the risk of hematoma expansion (RR = .8, 95% CI,.51-1.24; p = .31, I2 = 44%). It was also associated with a non-significant decrease in the risk of thrombotic events (RR,.83; 95% CI,.25-2.76; p = .76, I2 = 30%). However, patients in the DDAVP group demonstrated a significant increase in the risk of poor neurological outcomes (RR, 1.31; 95% CI, 1.07-1.61; p = .01, I2 = 0%). The risk of bias assessment showed a moderate to low level of risk. CONCLUSION: DDAVP was associated with a nonsignificant decrease in hematoma expansion and thrombotic events. However, it was also associated with a significantly poor neurological outcome in the patients. Thus, until more robust clinical trials are conducted, the use of DDAVP should be considered on a case-to-case basis.


Subject(s)
Deamino Arginine Vasopressin , Hematoma , Intracranial Hemorrhages , Platelet Aggregation Inhibitors , Deamino Arginine Vasopressin/adverse effects , Deamino Arginine Vasopressin/administration & dosage , Humans , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Intracranial Hemorrhages/chemically induced , Hematoma/chemically induced , Hemostatics/adverse effects , Hemostatics/administration & dosage
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