| 1. |
- Capodanno, Davide, et al.
(författare)
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Trial Design Principles for Patients a High Bleeding Risk Undergoing PCI JACC Scientific Expert Panel
- 2020
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 76:12, s. 1468-1483
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Tidskriftsartikel (refereegranskat)abstract
- Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting. (C) 2020 by the American College of Cardiology Foundation.
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| 2. |
- Madhavan, Mahesh V, et al.
(författare)
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Antiplatelet strategies in acute coronary syndromes: design and methodology of an international collaborative network meta-analysis of randomized controlled trials.
- 2021
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Ingår i: Minerva cardioangiologica. - 1827-1618. ; 69:4, s. 398-407
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Tidskriftsartikel (refereegranskat)abstract
- The optimal choice of oral P2Y12 receptor inhibitors has the potential to significantly influence outcomes. We seek to compare the safety and efficacy of the three most commonly used oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) in acute coronary syndromes (ACS) via a comprehensive systematic review and network meta-analysis.We will perform a comprehensive search for randomized clinical trials which compared cardiovascular and hemorrhagic outcomes after use of at least two of the distinct oral P2Y12 receptor inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor). In addition, key inclusion criteria will be trial size of at least 100 patients and at least 1 month of follow-up time. Several pre-specified subgroups will be explored, including Asian patients, patients presenting with ST-elevation myocardial infarction, patients of advanced age, and others.Exploratory frequentist pairwise meta-analyses will be based primarily on a random-effects method, relying on relative risks (RR) for short-term endpoints and incidence rate ratios (IRR) for long-term endpoints. Inferential frequentist network meta-analysis will be based primarily on a random-effects method, relying on RR and IRR as specified above. Results will be reported as point summary of effect, 95% CI, and p-values for effect, and graphically represented using forest plots.An international collaborative network meta-analysis has begun to comprehensively analyze the safety and efficacy of prasugrel, ticagrelor and clopidogrel, each on a background of aspirin, for management of patients with ACS. It is our hope that the rigor and breadth of the undertaking described herein will provide novel insights that will inform optimal patient care for patients with ACS treated conservatively, or undergoing revascularization.
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| 3. |
- Storey, Robert F., et al.
(författare)
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Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:33, s. 3132-3140
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Tidskriftsartikel (refereegranskat)abstract
- Aims To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y(12) receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). Methods and results In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y(12) reaction units (PRU) <100 at 30 min post-dose and lasting >= 3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean standard deviation) were 10 +/- 25 (8 mg), 4 +/- 10 (16 mg), and 163 +/- 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked similar to 30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). Conclusions Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y(12) inhibition sustained for >= 8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.
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| 4. |
- Angiolillo, Dominick J., et al.
(författare)
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European practice patterns for antiplatelet management in NSTE-ACS patients : Results from the REal-world ADoption survey focus on Acute antiPlatelet Treatment (READAPT) survey
- 2023
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Ingår i: International Journal of Cardiology. - 0167-5273. ; 386, s. 8-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The 2020 European Society of Cardiology (ESC) guidelines for the diagnosis and management of patients with non-ST elevation-acute coronary syndrome (NSTE-ACS) recommend early invasive coronary angiography in high-risk patients and no routine pre-treatment with oral P2Y12 receptor inhibitor in NSTE-ACS patients prior to defining coronary anatomy. Objective: To assess the implementation of this recommendation in the real-life setting. Methods: A web-survey in 17 European countries collected physician profiles and their perceptions of the diagnosis, medical and invasive management of NSTE-ACS patients at their hospital. A sample size of at least 1100 responders permitted the estimation of proportions with a precision of at least ±3.0%. Results: Among the 3024 targeted participants, 1154 provided valid feedback defined as a 50% response rate of answers to the survey questions. Overall, >60% of the participants declared full implementation of the guidelines at their institution. The time delay from admission to coronary angiography and PCI was reported to be <24 h in over 75% of the hospitals while pre-treatment was intended in >50% of NSTE-ACS patients. Ad-hoc percutaneous coronary intervention (PCI) was performed in >70% of the cases while intravenous platelet inhibition was rarely used (<10%). Between countries differences in practice patterns for antiplatelet management for NSTE-ACS were observed, suggesting heterogeneous implementation of the guidelines. Conclusions: This survey indicates that the implementation of 2020 NSTE-ACS guidelines on early invasive management and pre-treatment is heterogeneous, potentially due by local logistical constraints.
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| 5. |
- Capodanno, Davide, et al.
(författare)
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Bleeding avoidance strategies in percutaneous coronary intervention
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Nature. - 1759-5002 .- 1759-5010. ; 19:2, s. 117-132
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Tidskriftsartikel (refereegranskat)abstract
- For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such, in parallel with progress in device and drug development for PCI, there is clinical interest in developing strategies that maximize not only the efficacy but also the safety (for example, by minimizing bleeding) of any antithrombotic treatment or procedural aspect before, during or after PCI. In this Review, we discuss contemporary data and aspects of bleeding avoidance strategies in PCI, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens.
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| 6. |
- Capodanno, Davide, et al.
(författare)
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Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease : A Consensus Document from the Academic Research Consortium
- 2023
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 147:25, s. 1933-1944
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Tidskriftsartikel (refereegranskat)abstract
- Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.
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| 7. |
- Capodanno, Davide, et al.
(författare)
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Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease
- 2020
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 17:4, s. 242-257
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Forskningsöversikt (refereegranskat)abstract
- Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease. Many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. In this Review, Angiolillo and colleagues discuss the pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with cardiovascular disease.
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| 8. |
- Landi, Antonio, et al.
(författare)
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Antithrombotic therapy in patients with acute coronary syndrome : similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 13:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.
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| 9. |
- Laudani, Claudio, et al.
(författare)
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Short Duration of DAPT Versus De-Escalation After Percutaneous Coronary Intervention for Acute Coronary Syndromes
- 2022
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Ingår i: JACC. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 15:3, s. 268-277
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator.BACKGROUND: In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared.METHODS: Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity.RESULTS: Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a >95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses.CONCLUSIONS: In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile.
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| 10. |
- Sandner, Sigrid, et al.
(författare)
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Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.
- 2022
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Ingår i: JAMA. - 1538-3598. ; 328:6, s. 554-562
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Tidskriftsartikel (refereegranskat)abstract
- The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46).Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.
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| 11. |
- Sandner, Sigrid, et al.
(författare)
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One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.
- 2024
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Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1969-6213. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).
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