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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.
Clin Med (Lond) ; 24S: 100143, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38866466

ABSTRACT

 : This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been withdrawn at the request of the authors, editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.


Subject(s)
Acute Coronary Syndrome , Dual Anti-Platelet Therapy , Platelet Aggregation Inhibitors , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/adverse effects , Acute Coronary Syndrome/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Dual Anti-Platelet Therapy/methods , Male , Female , Middle Aged , Aged
4.
Acta Neurochir (Wien) ; 166(1): 262, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864938

ABSTRACT

PURPOSE: Each institution or physician has to decide on an individual basis whether to continue or discontinue antiplatelet (AP) therapy before spinal surgery. The purpose of this study was to determine if perioperative AP continuation is safe during single-level microsurgical decompression (MSD) for treating lumbar spinal stenosis (LSS) and lumbar disc hernia (LDH) without selection bias. METHODS: Patients who underwent single-level MSD for LSS and LDH between April 2018 to December 2022 at our institute were included in this retrospective study. We collected data regarding baseline characteristics, medical history/comorbidities, epidural hematoma (EDH) volume, reoperation for EDH, differences between preoperative and one-day postoperative blood cell counts (ΔRBC), hemoglobin (ΔHGB), and hematocrits (ΔHCT), and perioperative thromboembolic complications. Patients were divided into two groups: the AP continuation group received AP treatment before surgery and the control group did not receive antiplatelet medication before surgery. Propensity scores for receiving AP agents were calculated, with one-to-one matching of estimated propensity scores to adjust for patient baseline characteristics and past histories. Reoperation for EDH, EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complications were compared between the groups. RESULTS: The 303 enrolled patients included 41 patients in the AP continuation group. After propensity score matching, the rate of reoperation for EDH, the EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complication rates were not significantly different between the groups. CONCLUSION: Perioperative AP continuation is safe for single-level lumbar MSD, even without biases.


Subject(s)
Decompression, Surgical , Intervertebral Disc Displacement , Lumbar Vertebrae , Microsurgery , Platelet Aggregation Inhibitors , Spinal Stenosis , Humans , Female , Male , Spinal Stenosis/surgery , Middle Aged , Retrospective Studies , Lumbar Vertebrae/surgery , Aged , Decompression, Surgical/methods , Decompression, Surgical/adverse effects , Microsurgery/methods , Microsurgery/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Intervertebral Disc Displacement/surgery , Selection Bias , Herniorrhaphy/methods , Herniorrhaphy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Treatment Outcome , Perioperative Care/methods
5.
BMJ ; 385: e075707, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862179

ABSTRACT

OBJECTIVE: To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. DESIGN: Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial. SETTING: Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five year follow-up from August 2019 to June 2021. PARTICIPANTS: 500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary artery bypass grafting surgery and completed the DACAB trial. INTERVENTIONS: Patients were randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year, antiplatelet therapy was prescribed according to standard of care by treating physicians. MAIN OUTCOME MEASURES: The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings. RESULTS: Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% v 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses. CONCLUSIONS: Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy. TRIAL REGISTRATION: NCT03987373ClinicalTrials.gov NCT03987373.


Subject(s)
Aspirin , Coronary Artery Bypass , Platelet Aggregation Inhibitors , Ticagrelor , Humans , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Female , Male , Middle Aged , Ticagrelor/therapeutic use , Aspirin/therapeutic use , Aspirin/administration & dosage , Aged , Follow-Up Studies , Adult , Aged, 80 and over , Drug Therapy, Combination , Adolescent , Postoperative Complications/prevention & control , Treatment Outcome , Young Adult , China , Dual Anti-Platelet Therapy/methods
6.
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
7.
J Assoc Physicians India ; 72(4): 68-78, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38881086

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings. AIM: This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management. METHODS: A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis. RESULTS: The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, p < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI (p = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents (p < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, p < 0.001), 6-12 months for medium bleeding risk (48.8%, p < 0.001), and >12 months for low bleeding risk (65.6%, p < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, p < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management. CONCLUSION: The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.


Subject(s)
Cardiologists , Coronary Artery Disease , Dual Anti-Platelet Therapy , Platelet Aggregation Inhibitors , Humans , India , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Dual Anti-Platelet Therapy/methods , Coronary Artery Disease/drug therapy , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Practice Patterns, Physicians'/statistics & numerical data , Percutaneous Coronary Intervention/methods , Female , Male , Clinical Decision-Making
8.
Clin Transl Sci ; 17(6): e13862, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38877696

ABSTRACT

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.


Subject(s)
Atrial Fibrillation , Clopidogrel , Coronary Artery Bypass , Cytochrome P-450 CYP2C19 , Genotype , Platelet Aggregation Inhibitors , Platelet Aggregation , Postoperative Complications , Humans , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Atrial Fibrillation/etiology , Atrial Fibrillation/genetics , Atrial Fibrillation/epidemiology , Male , Female , Aged , Coronary Artery Bypass/adverse effects , Middle Aged , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation/drug effects , Incidence , Aspirin/administration & dosage , Aspirin/adverse effects
9.
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
10.
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
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
14.
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
15.
Expert Rev Cardiovasc Ther ; 22(6): 203-215, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38739469

ABSTRACT

INTRODUCTION: Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies. In the acute setting, the rationale for their use is to antagonize the ongoing clotting cascade including during percutaneous coronary intervention. Anticoagulation may be an important part of the longer-term antithrombotic strategy especially in patients who have other existing indications (e.g. atrial fibrillation) for their use. AREAS COVERED: In this narrative review, the authors provide a contemporary summary of the anticoagulation strategies of patients presenting with NSTEMI, both in terms of anticoagulation during the acute phase as well as suggested antithrombotic regimens for patients who require long-term anticoagulation for other indications. EXPERT OPINION: Patients presenting with non-ST-elevation myocardial infarction (NSTEMI) should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention. Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter.


Subject(s)
Anticoagulants , Fibrinolytic Agents , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Non-ST Elevated Myocardial Infarction/drug therapy , Fibrinolytic Agents/therapeutic use , Fibrinolytic Agents/administration & dosage , Drug Therapy, Combination , Time Factors
16.
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 , Factor Xa Inhibitors , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Adult , Aged , Female , Humans , Male , Middle Aged , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aspirin/administration & dosage , Aspirin/therapeutic use , Aspirin/adverse effects , Bioprosthesis , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/therapeutic use , Pyridones/administration & dosage , Pyridones/adverse effects , Randomized Controlled Trials as Topic , Thrombosis/prevention & control , Thrombosis/etiology , Time Factors , Treatment Outcome
17.
Sr Care Pharm ; 39(6): 212-217, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38803027

ABSTRACT

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.


Subject(s)
Aspirin , Deprescriptions , Pharmacists , Humans , Aspirin/therapeutic use , Aspirin/administration & dosage , Aged , Male , Female , Aged, 80 and over , Outpatients , Professional Role , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Primary Prevention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Ambulatory Care
18.
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
19.
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
20.
N Z Med J ; 137(1595): 64-72, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38754114

ABSTRACT

AIM: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) for patients without atrial fibrillation varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. Patients on DAPT with a high risk of gastrointestinal bleeding are also recommended to receive a proton pump inhibitor (PPI). Our aim was to audit current practice against the 2020 European Society of Cardiology (ESC) guideline recommendations. METHODS: One hundred consecutive ACS patients treated with percutaneous coronary intervention discharged from Middlemore Hospital and without atrial fibrillation in the first quarter of 2023 were studied. ANZACS-QI ischaemic (I) and bleeding (B) risk scores were calculated, with patients categorised in four groups based on ESC recommendations-low I/low B risk, low I/high B, high I/low B and high I/high B. Guideline and clinician recommended duration of DAPT and prescription of PPI were compared. RESULTS: All patients were planned for DAPT at discharge and 91% a PPI. Up to four out of five ACS patients could have been planned for shorter DAPT durations based on the ESC guideline recommendations. Over half of included patients (53%) had a high bleeding risk, yet 85% of these patients received 12 months of DAPT despite ESC recommendations of 1-3 months. CONCLUSIONS: There was a divergence between clinical practice and the recommendations of the 2020 ESC guidelines. We discuss these results in relation to the updated August 2023 ESC guidelines, which have reaffirmed a 12-month duration of DAPT as the default position.


Subject(s)
Acute Coronary Syndrome , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Practice Guidelines as Topic , Proton Pump Inhibitors , Humans , Acute Coronary Syndrome/drug therapy , Male , Female , Aged , Middle Aged , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Guideline Adherence , New Zealand , Gastrointestinal Hemorrhage/chemically induced
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