Afleveringen
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Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials
Med. 2024 Aug 10:S2666-6340(24)00301-5.doi: 10.1016/j.medj.2024.07.019.
Abstract
Background: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT).
Methods: Individual patient data were pooled from randomized clinical trials that included ST-elevation myocardial infarction STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) short-termdual antiplatelet therapy versus ticagrelor-based 12-month short-term dual antiplatelet therapy DAPT in terms of centrally adjudicated clinical outcomes. Theco-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding AcademicResearch Consortium type 3 or 5 bleeding) at 1 year.
Findings: The pooled cohort contained 2,253 patients with ST-elevation myocardial infarction. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based dual antiplatelet therapy group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%;HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups.
Conclusions: In patients with ST-elevationmyocardial infarction treated with drug-eluting stent implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients.
Disclaimer:
Lupin makes norepresentation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medicaljudgment, which you should exercise in evaluating the information on thiswebsite.
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Efficacy and Safety of P2Y12 monotherapy vs DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials
Curr Probl Cardiol. 2024 Aug;49(8):102635. doi: 10.1016/j.cpcardiol.2024.102635
Abstract
Background: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) afterpercutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short dual antiplatelet therapy (DAPT). However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard dual antiplatelet therapy DAPT in patients undergoing percutaneous coronary intervention PCI at 12 months.
Methods: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definitestent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).
Results: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both all cause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard dual antiplatelet therapy DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk ofmajor bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.
Conclusions: In comparison to standard dual antiplatelet therapy DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Zijn er afleveringen die ontbreken?
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Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study
Eur J Pediatr. 2024 Aug;183(8):3309-3317. doi: 10.1007/s00431-024-05597-1.
Abstract
Tetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatricintensive care unit. We included > 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgicalrepair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, low cardiac output syndrome scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patientsmet the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower low cardiac output syndrome scoresduring the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation.
Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative low cardiac output syndrome at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot.
What is Known: • Prevalence of low cardiacoutput syndrome is high following a late complete surgical repair of tetralogyof Fallot.
What is New: • Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome. • Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a latecomplete repair of tetralogy of Fallot, who are numerous in low-income countries.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Eligibility and Projected Benefits ofRapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure
JACC Heart Fail. 2024 Aug;12(8):1365-1377. doi: 10.1016/j.jchf.2024.03.001.
Abstract
Background: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized.
Objectives: This study sought to characterize the degree to which patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation.
Methods: Among patients hospitalizedfor newly diagnosed heart failure with reduced ejection fraction (HFrEF) in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibilitycriteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effectsfrom pivotal clinical trials utilized by the American HeartAssociation/American College of Cardiology /HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker andbeta-blockers.
Results: Of 33,036 patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF), 27,158(82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy,15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-monthincidence of mortality was 24.7% and Heart Failure hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensinreceptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no guideline-directed medical therapy.
Conclusions: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed heart failure with reduced ejection fraction (HFrEF), >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruplemedical therapy for newly diagnosed heart failure with reduced ejection fraction (HFrEF) would yield large absolute reductions in mortality.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Non-ST-elevation acute coronary syndromeswith previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management
Eur Heart J . 2024 Jul 12;45(27):2380-2391.doi: 10.1093/eurheartj/ehae245
Abstract
Background and aims: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup.
Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE , Cochrane, and ClinicalTrials.gov. Eligible studies were randomized controlled trials of routine invasive vs. a conservative or selective invasive strategy in patients presenting with non-ST-elevation acute coronary syndromes that included patients with previous coronary artery bypass graft. Summary data werecollected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.
Results: Summary data were obtained from 11 randomized controlled trials, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40).
Conclusions: This is the first meta-analysis assessing the effect of a routine invasive strategy in patientswith prior coronary artery bypass graft who present with non-ST-elevation acute coronary syndromes. The results confirm the under-representation of this patient group in randomized controlled trials of invasive management in non-ST-elevation acute coronary syndromes and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered randomized controlled trial.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry
https://doi.org/10.1002/ehf2.14927
Abstract
Aim
Anaemia has been reported as poor predictorin heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from dischargeto 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria.
Methods and results
First, 547 heart failure with preserved ejection fraction cases were divided into two groups, Hb < 11.0 g/dL (n= 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hbat discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curvethat predicts Major adverse cardiovascular events. We examined the incidence rate of Major adverse cardiovascular events between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb.In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR):3.14 [95% confidence interval (CI), 1.76–5.60], P < 0.001). Major adverse cardiovascular events was not significantly different between G2 with improving anaemia from Hb< 11.0 g/dL to ≥ 11.0 g/dL andG4 (adjusted HR: 1.37 [95%CI, 0.68–2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronicobstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR:1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). Inmultivariate linear regression analysis, covarying factors with change in Hb were BMI (β = −0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179).
Conclusions
Change in haemoglobin after discharge using alower cut-off value than World Health Organization criteria has prognostic impact in patients with heart failure with preserved ejection fraction.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor downregulates the expressionof proatherogenic and proinflammatory micro RNA 125-b compared to clopidogrel: A randomized, controlledtrial
Int J Cardiol . 2024 Jul 1:406:132073
Abstract
Background: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardialinfarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatorymicroRNAs, including microRNA -125a, microRNA -125b and microRNA-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.
Objectives: We compared miR -125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods: After percutaneous coronaryintervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel.Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 monthsof treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determineplatelet reactivity in response to P2Y12 inhibitors.
Results: Expression of miR-125b was higher inpatients with AMI 72 h and 6 months, compared to healthy volunteers (p =0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after acute myocardial infarction, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Clinical Pharmacogenetics ImplementationConsortium Guideline (CPIC) for CYP2D6, ADRB1,ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy
Clin Pharmacol Ther. 2024 Jul 1. doi: 10.1002/cpt.3351
Abstract
Beta-blockers are widely used medications fora variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic(e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. Wesearched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regardinggenetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendationsfor CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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The new ESC acute coronary syndrome guideline and its impact in the CPU and emergency department setting
Herz. 2024 Jun;49(3):185-189. doi: 10.1007/s00059-024-05241-6
The new guideline on acute coronary syndrome (ACS) of the European Society of Cardiology (ESC) replaces twoseparate guidelines on ST-elevation myocardial infarction (STEMI) and non-ST-elevation (NSTE) ACS . This change of paradigm reflects the experts view that the acute coronary syndrome is a continuum,starting with unstable angina and ending in cardiogenic shock or cardiac arrest due to severe myocardial ischemia. Secondary, partly non-atherosclerotic-causedmyocardial infarctions ("type 2") are not integrated in this concept. With respect to acute care in the setting of emergency medicine and the chest pain unit structures, the following new aspects have to be taken into account:
1. New procedural approach as "think acute coronary syndrome" meaning "abnormal ECG," "clinicalcontext," and "stable patient"
2. New recommendation regarding a holistic approach for frail patients
3. Revised recommendations regardingimaging and timing of invasive strategy in suspected non-ST elevation acute coronary syndrome.
4- Revised recommendations for antiplatelet and anticoagulant therapy in ST-elevation myocardial infarction
5. Revised recommendations for cardiac arrest and out-of-hospital cardiac arrest
6. Revised recommendations for in-hospital management (starting in the CPU/ED ) and acute coronary syndrome comorbid conditions.
In summary, the changes are mostly gradualand are not based on extensive new evidence, but more on focused and healthcare process-related considerations.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction
J Am Coll Cardiol. 2024 Jun 4;83(22):2135-2144
Abstract
Background: Total coronaryatherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes.
Objectives: We aimed to investigatewhether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction.
Methods: In this secondary analysisof an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction.
Results: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronaryrevascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10;Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions.
Conclusions: In patients with recentmyocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting trial
BMJ . 2024 Jun 11:385:e075707. doi:10.1136/bmj-2023-075707.
Abstract
Objective: To assess the effect ofdifferent 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 arterybypass grafting surgery and completed the Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting trial.
Interventions: Patients wererandomised 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 cardiovascularevents 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.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial
Am Heart J. 2024 Jun:272:11-22. doi:10.1016/j.ahj.2024.03.002
Abstract
Background: The optimal antiplateletregimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with peripheral artery disease undergoing percutaneous coronary intervention.
Methods: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent percutaneous coronary intervention were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of peripheral artery disease. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization.
Results: Among 7,119 patients, 489 (7%) had peripheral artery disease and were older, more likely to havecomorbidities, and multivessel disease. Peripheral artery disease patients had more bleeding or ischemic complications than no- peripheral artery diseasepatients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in peripheral artery disease (4.6% vs 8.7%; HR 0.52; 95%Cl 0.25-1.07) and no- peripheralartery disease patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, myocardial infarction, or stroke in these 2 groups (interaction P-value .446).
Conclusions: Despite their higher ischemicand bleeding risk, patients with Peripheral artery disease undergoing percutaneous coronary intervention derived a consistent benefit from ticagrelor monotherapy after 3 months of dual antiplatelet therapy in terms of bleedingreduction without any relevant increase in ischemic events.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study
Catheter Cardiovasc Interv . 2024 May;103(6):897-908. doi: 10.1002/ccd.31030
Abstract
Background: Acute kidney injury (AKI) is a frequentand potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction(STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined.
Methods: We queried the National Inpatient Sample(2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated usingsubgroup analysis and interaction testing.
Results: A total of 62,599 (weighted nationalestimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients wereon average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence(adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patientsincreased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all).
Conclusions: Obesity was independently associatedwith a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.
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Management of Severe Mitral Regurgitation in Patients With Acute Myocardial Infarction: JACC Focus Seminar 2/5
J Am Coll Cardiol . 2024 May 7;83(18):1799-1817. doi:10.1016/j.jacc.2023.09.840
Abstract
Severe acute mitral regurgitation after myocardialinfarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. Thisreview focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patientmanagement and eventually decrease mortality.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Tolerability and effectiveness of beta-blockers in patients with cardiac amyloidosis: A systematic review and meta-analysis
Int J Cardiol . 2024 May 1:402:131813. doi:10.1016/j.ijcard.2024.131813
Abstract
Objective: This systematic review aimed to assess thetolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse outcomes.
Methods: We performed a comprehensive search fromJanuary 1, 2000 to October 20, 2023. Studies examining BB use and tolerance or the relationship between BB use and outcomes in patients with CA were included. Pooled adjusted hazard ratios (aHRs) for all-cause mortality were calculated using random- and fixed-effects models.
Results: Eight observational studies involving 4002patients with CA (87.5% with transthyretin CA [ATTR-CA] and 12.5% with immunoglobulin light chain CA [AL-CA]) were assessed. BBs were used by 52.5% of the patients.However, 26.3% of the patients discontinued BBs because of hypotension, bradycardia, or fatigue. Regarding the association between BB use and all-causedeath, four studies were identified that included 2874 patients with ATTR-CA and 16 patients with AL-CA. The meta-analysis revealed no apparent relationship between BB use and all-cause mortality (pooled aHR = 0.78, 95% confidence interval (CI) = 0.40-1.51). Two studies on patients with ATTR-CA found no impact of BB use on all-cause mortality in the subgroup with left ventricular ejection fraction (LVEF) > 40%, but conflicting results exist for those with LVEF ≤40% (pooled aHR = 0.78, 95% CI = 0.40-1.54).
Conclusion: The limited number of observationalstudies that predominantly enrolled patients with ATTR -CA showed that BBs were used in almost half of the patients with CA, with varying tolerability. However, no significant association was observed between BB use and all-cause mortality.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomized, placebo-controlled, double-blind clinical trial
Randomized Controlled Trial Lancet . 2024 May 11;403(10439):1866-1878. doi: 10.1016/S0140-6736(24)00473-2.
Abstract
Background: Following percutaneous coronaryintervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapywith aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months afterpercutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE).
Methods: In this randomized, placebo-controlled,double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic orbleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents.Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamicminimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). Theprimary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, orclinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months afterpercutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesistesting of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population.
Findings: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients toticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) inthe ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39];pnon-inferiority<0·0001, psuperiority=0·89).
Interpretation: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy,treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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The application value of Metoprolol combined with Dagalizin in enhancing cardiac function and ventricularremodeling in patients with acute myocardial infarction after percutaneous coronary intervention.
J Clin Emerg, 2024, 25(4): 170-174. doi:10.13201/j.issn.1009-5918.2024.04.003
Abstract
To discuss the application value of metoprolol combined with daglizin in improving cardiac function and ventricular remodeling in patients with acute myocardial infarction(AMI) after percutaneous coronary intervention(PCI).
A total of 86 patients with acute myocardial infarction I- percutaneous coronary intervention from January 2022 to October 2023 were selected and divided into experimental group(43 cases) and control group(43 cases) according to a random table. Patients in the control group were given metoprolol + conventional treatment and patients in the experimental group were given combined treatment with daglizin on this basis. The cardiac function(left ejection fraction[LVEF], heart index[CI], stroke output[SV]), ventricular remodeling(left ventricular end-diastolic volume[LVEDV], left ventricularend-systolic volume[LVESV], left ventricular end-diastolic diameter[LVEDD]) and laboratory parameters(N-terminal B-type natriuretic peptideprecursor[NT-proBNP], hypersensitive C-reactive protein[hs-CRP], interleukin-6[IL-6]), adverse cardiovascular events and adverse events were compared between the two groups.
After treatment, the left ejection fraction, heart index and stroke output of the two groups were significantly higher than those before treatment, and the left ejection fraction, heart index and stroke output in the experimental group were significantly higher than those in the control group(P < 0.05). After treatment, the Left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular end-diastolic diameter,N-terminal B-type natriuretic peptide precursor, hypersensitive C-reactive protein and interleukin-6of the two groups were significantly lower than those before treatment, and Left ventricular end-diastolic volume, left ventricular end-systolic volume, leftventricular end-diastolic diameter, N-terminal B-type natriuretic peptide precursor, hypersensitive C-reactive protein and interleukin-6in the experimental group were significantly lower than those in the control group(P < 0.05). The incidence of adverse cardiovascular events in the experimental group was significantly lower than that in the control group(P < 0.05). The adverse events rate of the two groups was basically the same(P>0.05).
Metoprolol combined with daglizin can improve cardiacfunction and ventricular remodeling in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention(PCI), which is beneficial for prognosis improvement, and it is worthy of clinical promotion.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website
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Impact of cardiac rehabilitation on ventricular-arterial coupling and left ventricular function in patients withacute myocardial infarction
PLoS One . 2024 Apr 4;19(4):e0300578. doi:10.1371/journal.pone.0300578
Abstract
To maintain efficient myocardial function, optimalcoordination between ventricular contraction and the arterial system is required. Exercise-based cardiac rehabilitation (CR) has been demonstrated toimprove left ventricular (LV) function. This study aimed to investigate the impact of cardiac rehabilitation on ventricular-arterial coupling (VAC) and its components, as well as their associations with changes in LV function in patients with acute myocardial infarction (AMI) and preserved or mildly reduced ejection fraction (EF). Effective arterial elastance (EA) and index (EAI) werecalculated from the stroke volume and brachial systolic blood pressure. Effective left ventricular end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. The characteristic impedance (Zc) of the aortic root was calculated after Fourier transformation of both aortic pressure and flow waveforms. Pulse wave separation analysis was performed to obtain the reflection magnitude (RM). An exercise-based, outpatient cardiac rehabilitation(CR) program was administered for up to 6 months. Twenty-nine patients were studied. However, eight patients declined to participate in the cardiac rehabilitation program and were subsequently classified as the non- cardiac rehabilitation group. At baseline, E' velocity showed significant associations with EAI (beta -0.393; P = 0.027) and VAC (beta -0.375; P =0.037). There were also significant associations of LV global longitudinal strain (LV GLS) with EAI (beta 0.467;P = 0.011). Follow-up studies after a minimum of 6 months demonstrated a significant increase in E' velocity (P = 0.035), improved EF (P = 0.010), andLV GLS (P = 0.001), and a decreased EAI (P = 0.025) only in the cardiac rehabilitation group. Changes in E' velocitywere significantly associated with changes in EAI (beta -0.424; P = 0.033). Increased aortic afterload and ventricular-arterial mismatch were associated with a negative impact on both left ventricular diastolic and systolic function. The outpatient cardiac rehabilitation program effectively decreased aortic afterload and improved left ventricular diastolic and systolic dysfunction in patients with acute myocardial infarction and preserved or mildly reduced Ejection Fraction.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website
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Prognostic Impact of Early Administration of β-Blockers in Critically Ill Patients with Acute Myocardial Infarction
J Clin Pharmacol . 2024 Apr;64(4):410-417.doi: 10.1002/jcph.2370.
Abstract
In critically ill patients with acute myocardialinfarction (AMI), the relationship between the early administration of β-blockers and the risks of in-hospital and long-term mortality remains controversial. Furthermore, there are conflicting evidences for the efficacy of the early administration of intravenous followed by oral β-blockers in acute myocardial infarction. We conducted a retrospective analysis of critically ill patients with acute myocardial infarction who received the early administration of β-blockers within 24 hours of admission. The data were extracted from the Medical Information Mart for Intensive Care IV database. We enrolled 2467 critically ill patients with AMI in the study, with 1355 patients who receivedthe early administration of β-blockers and 1112 patients who were non-users. Kaplan-Meier survival analysis and Cox proportional hazards models showed that the earlyadministration of β-blockers was associated with a lower risk of in-hospital mortality (adjusted hazardratio [aHR] 0.52; 95% confidence interval [95%CI] 0.42-0.64), 1-year mortality (aHR 0.54, 95%CI 0.47-0.63), and 5-year mortality (aHR 0.60, 95%CI0.52-0.69). Furthermore, the early administration of both oral β-blockers and intravenous β-blockers followed by oral β-blockers may reduce the mortality risk, compared with non-users. The risks of in-hospital and long-term mortality were significantly decreased in patients who underwent revascularization with the early administration of β-blockers. We found thatthe early administration of β-blockers could lower the risks of in-hospital and long-term mortality. Furthermore, the early administration of both oral β-blockers and intravenous β-blockers followed by oral β-blockers may reduce the mortality risk, compared with non-users. Notably, patients who underwent revascularization with the early administration of β-blockers showed the lowest risks of in-hospital and long-term mortality.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website
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Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention
J Endocrinol Invest. 2024 Apr;47(4):895-902.doi: 10.1007/s40618-023-02205-1
Abstract
Purpose: Patients with coronary artery disease haveincreased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dualanti-platelet therapy (DAPT).
Methods: We identified all adults who underwentfirst-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong.Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes ofinterest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for major osteoporotic fractures associated with ticagrelor versus clopidogrel use.
Results: 3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained major osteoporotic fractures (annualized fracture risks: 0.34 % and 0.56%, respectively).Ticagrelor use was associated with lower risks of major osteoporotic fractures (HR 0.60, 95%CI 0.44-0.83; p =0.002). Consistent hazard ratios were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history.
Conclusion: Among adults who underwent first-ever percutaneous coronary intervention for acute coronary syndrome, ticagrelor use in the dual anti-platelet therapy was associated with a lower risk of major osteoporoticfractures compared with clopidogrel. Our results support the use of ticagrelor in the dual anti-platelet therapy from the perspective of bone health.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STARUPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the informationon this website
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