-
International Journal of Molecular... May 2024This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial... (Review)
Review
This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.
Topics: Humans; Adenosine; Coronary Artery Disease; Animals; Adenosine Monophosphate; Platelet Aggregation Inhibitors
PubMed: 38892037
DOI: 10.3390/ijms25115852 -
Open Heart Jun 2024For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the... (Comparative Study)
Comparative Study
BACKGROUND
For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel polymer-free biolimus-coated stent (SS-BCS) with 30 days of dual antiplatelet treatment (DAPT). The LEADERS FREE III (LF III) trial investigated clinical outcomes after PCI with the next-generation cobalt-chromium thin-strut polymer-free biolimus-coated stent (CoCr-BCS) in HBR patients.
AIMS
To report the final 3-year results of the LF III trial and compare them to LF II.
METHODS
LF III was a prospective, multicentre, open-label single-arm study to evaluate the safety and efficacy of the CoCr-BCS stent. The primary safety endpoint was the composite of cardiac death (CD), myocardial infarction(MI) or definite/probable stent thrombosis (ST). The primary efficacy endpoint was clinically driven target lesion revascularisation (cd-TLR). We performed a propensity-matched comparison to the 3-year outcomes of LF II.
RESULTS
After 3 years, CD/MI/ST had occurred in 57 patients (15%, 95% CI 11.8% to 19%) and cd-TLR in 23 (6.2%, 95% CI 4.1% to 9.2%) patients. In a propensity-matched comparison of patients treated with the CoCr-BCS versus the SS-BCS, there were similar rates of CD (6.6% vs 7.8%, p=0.50), MI (7.1% vs 8.3%, p=0.47) and definite/probable ST (1.1% vs 2%, HR 0.56, 95% CI 0.16 to 1.93, p=0.35). The rates of cd-TLR were 5.3% with CoCr-BCS versus 9.8% with SS-BCS (HR 0.54, 95% CI 0.31 to 0.96, p=0.03).
CONCLUSION
LF III confirms the long-term safety and efficacy of the CoCr-BCS in HBR patients treated with 1 month of DAPT.
TRIAL REGISTRATION NUMBER
NCT02843633, NCT03118895.
Topics: Humans; Drug-Eluting Stents; Male; Prospective Studies; Female; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Treatment Outcome; Coronary Artery Disease; Aged; Time Factors; Middle Aged; Follow-Up Studies; Platelet Aggregation Inhibitors; Risk Factors
PubMed: 38890129
DOI: 10.1136/openhrt-2024-002679 -
EuroIntervention : Journal of EuroPCR... Jun 2024
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Percutaneous Coronary Intervention; Treatment Outcome
PubMed: 38887879
DOI: 10.4244/EIJ-E-24-00009 -
Digital Health 2024The emergence of cardiovascular risk factors in sub-Saharan Africa suggests an increasing incidence of acute coronary syndromes and STEMI. The aim of the study was to...
INTRODUCTION
The emergence of cardiovascular risk factors in sub-Saharan Africa suggests an increasing incidence of acute coronary syndromes and STEMI. The aim of the study was to define the prevalence of STEMI and to describe the characteristics of patients diagnosed with STEMI within the tele-electrocardiogram (ECG) network in Côte d'Ivoire.
METHOD
A retrospective study was conducted from January 2015 to August 2019. All adult patients managed by one of the six hospitals within the telemedicine network who benefited from a remote interpretation of their ECG by the cardiology department of Bouaké University Hospital were included. The main reason for ECG interpretation, patient and ECG characteristics, diagnosis, response time and treatment were described.
RESULTS
A total of 5649 patients were included. The prevalence of STEMI was 0.7% ( = 44 cases) with a mean age of 58.6 ± 11.8 years and a M/F sex ratio of 1.93. Among STEMI patients, chest pain was the main reason for ECG testing (56.8%). Most ECGs were interpreted within 12 hours (72.8%). The anterior inter-ventricular artery location (59.1%, = 26) was predominant. The Q wave of necrosis was absent in 18% ( = 8) of cases. All patients received double anti-platelet aggregation and 50% ( = 22) additional heparin therapy. No patient underwent primary angioplasty or thrombolysis, 65.9% ( = 29) were referred to the Bouaké Cardiology Department and 34.1% ( = 15) to the Abidjan Heart Institute. Scheduled angioplasty was performed in 20% ( = 3) of patients in Abidjan.
CONCLUSION
Tele-ECG was an effective means of STEMI screening in Côte d'Ivoire. Systematic telethrombolysis of all patients diagnosed could improve their prognosis.
PubMed: 38882247
DOI: 10.1177/20552076241262276 -
Clinical and Translational Science Jun 2024This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral...
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.
Topics: Humans; Cytochrome P-450 CYP2C19; Atrial Fibrillation; Male; Female; Aged; Coronary Artery Bypass; Middle Aged; Clopidogrel; Postoperative Complications; Genotype; Platelet Aggregation Inhibitors; Platelet Aggregation; Incidence; Aspirin
PubMed: 38877696
DOI: 10.1111/cts.13862 -
Journal of the American Heart... Jun 2024Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention...
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
METHODS AND RESULTS
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS
Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Black or African American; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38874073
DOI: 10.1161/JAHA.123.033791 -
Clinical and Applied... 2024Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk...
BACKGROUND
Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk of aspirin-induced bleeding and carefully balancing its benefits against potential risks. The objective of this study was to create a practical nomogram for predicting bleeding risk in patients with a history of myocardial infarction treating with aspirin.
METHODS
A total of 2099 myocardial infarction patients with aspirin were enrolled. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation. Boruta analysis was utilized to identify clinically significant features associated with bleeding. Logistic regression model based on independent bleeding risk factors was constructed and presented as a nomogram. Model performance was assessed from three aspects: identification, calibration, and clinical utility.
RESULTS
Boruta analysis identified eight clinical features from 25, and further multivariate logistic regression analysis selected four independent risk factors: hemoglobin, platelet count, previous bleeding, and sex. A visual nomogram was created based on these variables. The model achieved an area under the curve of 0.888 (95% CI: 0.845-0.931) in the training dataset and 0.888 (95% CI: 0.808-0.968) in the test dataset. Calibration curve analysis showed close approximation to the ideal curve. Decision curve analysis demonstrated favorable clinical net benefit for the model.
CONCLUSIONS
Our study focused on creating and validating a model to evaluate bleeding risk in patients with a history of myocardial infarction treated with aspirin, which demonstrated outstanding performance in discrimination, calibration, and net clinical benefit.
Topics: Humans; Nomograms; Myocardial Infarction; Aspirin; Hemorrhage; Female; Male; Middle Aged; Aged; Risk Factors; Platelet Aggregation Inhibitors; Risk Assessment
PubMed: 38870349
DOI: 10.1177/10760296241262789 -
Clinical Medicine (London, England) Apr 2024: This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has...
: 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.
Topics: Humans; Proton Pump Inhibitors; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Male; Female; Middle Aged; Aged
PubMed: 38866466
DOI: 10.1016/j.clinme.2024.100143 -
BMC Infectious Diseases Jun 2024Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and...
BACKGROUND
Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and treatment, possess recently discovered anti-inflammatory properties, raising potential for improved sepsis prognosis.
METHOD
We conducted a retrospective analysis using the data from Medical Information Mart for Intensive Care-IV database. Patients were divided into an aspirin-alone group versus a combination group based on the use of a P2Y12 inhibitor or not. Differences in 30-day mortality, length of stay (LOS) in intensive care unit (ICU), LOS in hospital, bleeding events and thrombotic events were compared between the two groups.
RESULT
A total of 1701 pairs of matched patients were obtained by propensity score matching. We found that no statistically significant difference in 30-day mortality in aspirin-alone group and combination group (15.3% vs. 13.7%, log-rank p = 0.154). In addition, patients received P2Y12 inhibitors had a higher incidence of gastrointestinal bleeding (0.5% vs. 1.6%, p = 0.004) and ischemic stroke (1.7% vs. 2.9%, p = 0.023), despite having a shorter LOS in hospital (11.1 vs. 10.3, days, p = 0.043). Cox regression showed that P2Y12 inhibitor was not associated with 30-day mortality (HR = 1.14, 95% CI 0.95-1.36, p = 0.154).
CONCLUSION
P2Y12 inhibitors did not provide a survival benefit for patients with sepsis 3 and even led to additional adverse clinical outcomes.
Topics: Humans; Male; Female; Sepsis; Aspirin; Retrospective Studies; Propensity Score; Aged; Middle Aged; Purinergic P2Y Receptor Antagonists; Length of Stay; Intensive Care Units; Treatment Outcome; Aged, 80 and over; Platelet Aggregation Inhibitors
PubMed: 38862910
DOI: 10.1186/s12879-024-09421-x -
BMJ (Clinical Research Ed.) Jun 2024To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. (Randomized Controlled Trial)
Randomized Controlled Trial
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% 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% 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.
Topics: Humans; Coronary Artery Bypass; Platelet Aggregation Inhibitors; Female; Male; Middle Aged; Ticagrelor; Aspirin; Aged; Follow-Up Studies; Adult; Aged, 80 and over; Drug Therapy, Combination; Adolescent; Postoperative Complications; Treatment Outcome; Young Adult; China; Dual Anti-Platelet Therapy
PubMed: 38862179
DOI: 10.1136/bmj-2023-075707