High platelet reactivity – the challenge of prolonged anticoagulation therapy after ACSI

2013 ◽  
Vol 109 (05) ◽  
pp. 799-807 ◽  
Author(s):  
Marc A. Brouwer ◽  
Freek W. A. Verheugt ◽  
Jeroen Focks
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Adjunctive Therapy ◽  
Platelet Reactivity ◽  
Vitamin K Antagonists ◽  
Antiplatelet Agent ◽  
Anticoagulation Therapy ◽  
High Platelet Reactivity ◽  
Coronary Syndrome ◽  
The Impact

SummaryDespite dual antiplatelet therapy (DAPT), one-year event rates after acute coronary syndrome (ACS) vary from 9–12%. The development of novel oral anticoagulants (NOAC) without a need for monitoring has initiated renewed interest for prolonged adjunctive anticoagulation. Importantly, the cornerstone of treatment after ACS consists of long-term DAPT. In that context, the NOACs have only been tested as adjunctive therapy. Of all new agents, only rivaroxaban –in a substantially lower dose than used for atrial fibrillation– has been demonstrated to improve outcome, albeit at the cost of bleeding. In selected cases, adjunctive therapy with dose-adjusted vitamin-K antagonists (international normalized ratio [INR] 2.0–3.0) can be considered as well. These two strategies of prolonged anticoagulation can be considered in case of ‘high platelet reactivity’, i.e. in patients at high risk of recurrent thrombotic events despite DAPT. Both during admission and after discharge for ACS, the use of NOACs in doses indicated for atrial fibrillation is strictly contra-indicated in patients on DAPT. In case of post-discharge anticoagulation therapy for atrial fibrillation, patients should preferably receive vitamin-K antagonists (INR 2.0–3.0), with discontinuation of one antiplatelet agent as soon as clinically justifiable. Importantly, the impact of prolonged anticoagulation (low-dose rivaroxaban, vitamin-K antagonists) as adjunctive to DAPT after ACS has not been addressed with the most potent antiplatelet agents (prasugrel, ticagrelor) and merits further study. Despite the potential indication of prolonged oral anticoagulation as adjunctive treatment, it remains to be established whether anticoagulation therapy could also be an alternative for either aspirin or thienopyridine treatment in selected ACS patients on DAPT.

scholarly journals Antithrombotic strategy in patients with atrial fibrillation and acute coronary syndrome

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
I Almeida ◽  
H Santos ◽  
M Santos ◽  
H Miranda ◽  
J Chin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Antithrombotic Therapy ◽  
De Novo ◽  
Vitamin K Antagonists ◽  
Antiplatelet Agent ◽  
P2y12 Inhibitors ◽  
Coronary Syndrome ◽  
Short Period ◽  
St Elevation

Abstract Background Atrial fibrillation (AF) is frequent in patients admitted with acute coronary syndromes (ACS). The development of this arrhythmia occurs in 2–21% of patients with non ST-elevation ACS and 21% of ST-elevation ACS. According with the most recent European guidelines, a short period up to 1 week of triple antithrombotic therapy (TAT) is recommended, followed by dual antithrombotic therapy (DAT) using a NOAC and a single antiplatelet agent, preferably clopidogrel. Objective To compare the antithrombotic strategy (DAT vs TAT) used and its prognostic value in patients with AF and ACS. Methods Retrospective analysis of patients' data admitted with ACS in a multicentric registry between 10/2010–09/2019. TAT was defined as the prescription of dual antiplatelet therapy and one anticoagulant and DAT as one antiplatelet and one anticoagulant. Survival and rehospitalization were evaluated through Kaplan-Meier curve. Results 1067 patients were included, mean age 67±14 years, 72.3% male. Patients who developed de novo AF during hospitalization due to ACS were older (75±12 vs 66±14 years, p<0.001) and with higher prevalence of cardiovascular risk factors and cardiovascular disease. AF was more often in patients with ST elevation ACS (53.4%). During hospitalization, AF patients were more often medicated with aspirin, glycoprotein inhibitor, heparin, fondaparinux and vitamin K antagonists. No difference was found regarding P2Y12 inhibitors. AF patients presented more often obstructive coronary disease (normal coronaries 5.4 vs 8.5%, p<0.001) so they were more often submitted to PCI (79.5 vs 70.9%, p<0.001). AF patients presented with higher rates of adverse in-hospital events as re-infarction, heart failure, shock, ventricular arrhythmias, cardiac arrest, stroke, major bleeding and death (p<0.001). At discharge, AF patients were less prescribed with aspirin or ticagrelor, but the rate of clopidogrel prescription was higher, such as vitamin K antagonists or any of the new anticoagulants. In the AF group, 21.5% patients were discharged with TAT and 30.3% with DAT. Concerning patients discharged with TAT, 1-year follow-up revealed no significant differences in mortality (p=0.578), re-admission for cardiovascular causes (p=0.301) and total re-admission rates (p=0.291). Patients discharged with DAT had similar mortality (p=0.623) and re-admission for cardiovascular causes rates (p=0.138), but significant differences were identified regarding total re-admissions (p=0.024). Conclusions In patients with ACS and de novo AF, a low percentage of patients was discharged with oral anticoagulation (51.8%). In those whose anticoagulation was initiated, DAT was the preferred strategy. 1-year outcomes were not different between the antithrombotic strategy, except for all cause re-admission. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

2021 ◽  
Vol 10 (15) ◽  
pp. 3212
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Laura Piccioni ◽  
Carmelo Massimiliano Rao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Advance ◽  
Thromboembolic Events ◽  
Thromboembolic Risk ◽  
Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

scholarly journals Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients with Atrial Fibrillation After Acute Coronary Syndrome or PCI: Insights from The AUGUSTUS Trial

Circulation ◽  
2021 ◽  
Author(s):  
Ziad Hijazi ◽  
John H. Alexander ◽  
Zhuokai Li ◽  
Daniel M. Wojdyla ◽  
Roxana Mehran ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Kidney Function ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Exclusion Criterion ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Ischemic Events

Background: In the AUGUSTUS trial, apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists (VKA), and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y 12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. Methods: In 4456 patients, the CKD-EPI formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban vs. VKA and aspirin vs. placebo was assessed across kidney function categories using Cox models. The primary outcome was ISTH major or clinically relevant non-major bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance below 30 mL/min was an exclusion criterion in the AUGUSTUS trial. Results: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30-50 mL/min/1.73m 2 , respectively. During 6-months follow-up a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with VKA, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30-50 mL/min/1.73m 2 for bleeding events with rates of 13.1% vs. 21.3%; HR (95% CI) 0.59 (0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL/min/1.73m 2 : 16.6% vs. 5.6%; HR 3.22 (2.19-4.74); p for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable with aspirin and placebo across eGFR categories with HR ranging from 0.97 (0.76-1.23) to 1.28 (1.02-1.59) and from 0.75 (0.48-1.17) to 1.34 (0.81-2.22), respectively. Conclusions: The safety and efficacy of apixaban was consistent irrespective of kidney function, as compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02415400

Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern

2020 ◽  
Vol 145 (14) ◽  
pp. 978-986
Author(s):  
Harald Darius
Keyword(s):  
Triple Therapy ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Antiplatelet Agent ◽  
Current Status ◽  
Bleeding Complications ◽  
Coronary Syndrome ◽  
Coronary Stent Implantation ◽  
Number Of Patients

AbstractThe number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and an indication for oral anticoagulation (OAC) for the prevention of strokes increases, who are in need for a dual antiplatelet therapy (DAPT) with acetyl salicylic acid (ASA) plus a P2Y12-Inhibitor because of an acute coronary syndrome and/or coronary stent implantation. These patients did receive a triple therapy (TT) for 3–12 months in the past. Triple therapy never has been studied for efficacy or safety, however, the rate of bleeding complications in comparison to OAC or DAPT is significantly higher.Registries and smaller trials showed that dual therapy with an OAC plus a single platelet inhibitor may be sufficient to prevent strokes and stent thromboses/myocardial infarctions. Four prospective randomized trials involving all four NOACs (Non-Vitamin K oral anticoagulants) approved for stroke prevention in AF have been undertaken. The NOACs plus one antiplatelet agent were tested versus vitamin K-antagonists plus DAPT. In the meantime, the trials involving rivaroxaban (PIONEER AF-PCI), dabigatran (RE-DUAL PCI), apixaban (AUGUSTUS), and edoxaban (ENTRUST-AF-PCI) have been published. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with respect to the bleeding complications, without any obvious and statistically significant disadvantage for stroke rates or cardiac ischemic events. The international guidelines already recommend to treat with a NOAC and one antiplatelet agent instead of TT in case the patients bleeding risk is prevailing. Thus, TT seems not to be indicated anymore for most patients with AF and ACS or PCI.

scholarly journals 2021 Korean Heart Rhythm Society Guidelines for Stroke Prevention in Atrial Fibrillation

2021 ◽  
Vol 96 (4) ◽  
pp. 296-311
Author(s):  
Ki Hong Lee ◽  
Jin-Bae Kim ◽  
Seung Yong Shin ◽  
Boyoung Joung
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Optimal Strategies ◽  
Mechanical Valve ◽  
Heart Rhythm ◽  
Bleeding Risk

Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.

scholarly journals Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study

TH Open ◽  
2019 ◽  
Vol 03 (04) ◽  
pp. e316-e324 ◽  
Author(s):  
Raza Alikhan ◽  
Cinira Lefevre ◽  
Ian Menown ◽  
Steven Lister ◽  
Alex Bird ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Recurrent Bleeding ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
The Impact

Abstract Background There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds. Objective To estimate the impact of bleeding events on the risk of subsequent bleeds, venous thromboembolism (VTE), stroke, and myocardial infarction (MI) among patients initiating VKA treatment for new-onset nonvalvular atrial fibrillation (NVAF). Methods We conducted an observational cohort study using a linked Clinical Practice Research Datalink—Hospital Episode Statistics dataset. Among a cohort of individuals with NVAF, the risk of clinically relevant bleeding, VTE, stroke, and MI was compared between the period prior to the first bleed and the periods following each subsequent bleed. The rate and cost of general practitioner (GP) consultations, prescriptions, and hospitalizations were also compared across these periods. Results The risk of clinically relevant bleeding events was observed to be elevated at least twofold in all periods following the first bleeding event. The risk of VTE, stroke, and MI was not found to differ according to the number of clinically relevant bleeding events. The rate and cost of GP consultations, GP prescriptions, and hospitalizations were increased in all periods relative to the period prior to the first bleed. Conclusions The doubling in the risk of bleeding following the first bleed, taken alongside the stable risk of MI, VTE, and stroke, suggests that the risk–benefit balance for VKA treatment should be reconsidered following the first clinically relevant bleed.

P4783Treatment persistence of patients with atrial fibrillation on VKA or NOAC: Data from GLORIA-AF Phase III 1-year interim analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Y H Lip ◽  
H.-C Diener ◽  
S J Dubner ◽  
J L Halperin ◽  
K J Rothman ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Interim Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Treatment Persistence ◽  
Geographical Regions ◽  
Dosing Regimens ◽  
The Impact

Abstract Background Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program. Methods Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation. Results Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02). Conclusion In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence. Acknowledgement/Funding The GLORIA-AF Registry program was funded by Boehringer-Ingelheim

Atrial Fibrillation and Malignancy: The Clinical Performance of Non–Vitamin K Oral Anticoagulants—A Systematic Review

2018 ◽  
Vol 45 (02) ◽  
pp. 205-214 ◽  
Author(s):  
Roberta Bottino ◽  
Anna Rago ◽  
Pierpaolo Micco ◽  
Antonio D' Onofrio ◽  
Biagio Liccardo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Vitamin K ◽  
Clinical Performance ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Therapeutic Anticoagulation ◽  
Increased Risk ◽  
Active Cancer

AbstractAtrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2DS2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.

scholarly journals Anticoagulation therapy in the elderly with non-valvular atrial fibrillation: a double-edged sword

2017 ◽  
Vol 3 (2) ◽  
Author(s):  
Francesco Vetta ◽  
Gabriella Locorotondo ◽  
Giampaolo Vetta
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Treatment Strategies ◽  
The Elderly ◽  
Hemorrhagic Events

Prevalence of non-valvular atrial fibrillation is increasing over time. Particularly in elderly population, treatment strategies to reduce the rate of stroke are challenging and still represent an unsolved cultural question. Indeed, the risk of thromboembolism increases in the elderly in parallel with the risk of bleeding. The frequent coexistence of several morbidities, frailty syndrome, polypharmacy, chronic kidney disease and dementia strengthens the perception that risk-benefit ratio of anticoagulant therapy could be unfavorable, and explains why such treatment is underused in the elderly. Recently, the introduction of non-vitamin K oral anticoagulants (NOACs) has allowed us to overcome the large number of limitations imposed by the use of vitamin K antagonists. In this manuscript, the benefits of individual NOACs in comparison with warfarin in elderly patients are reviewed. Targeted studies on complex elderly patients are needed to test usefulness of a geriatric comprehensive assessment, besides the scores addressing risk of thromboembolic and hemorrhagic events. In the meantime, it is mandatory that use of anticoagulant therapy in most elderly people, currently excluded from randomized controlled trials, is prudent and responsible.

scholarly journals Stroke prevention for non-valvular atrial fibrillation: how to make the right choice of directly acting oral anticoagulants?

2019 ◽  
pp. 94-102
Author(s):  
N. N. Kryukov ◽  
E. V. Sayutina ◽  
A. M. Osadchuk ◽  
M. A. Osadchuk
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Individual Risk ◽  
Stroke Risk Factor ◽  
Coronary Syndrome

Patients with atrial fibrillation have a high risk of developing stroke and death, which requires constant anticoagulant support. In this regard, the physician faces the difficult task of selecting the appropriate oral anticoagulant for patient with individual risk factors and comorbidities. Currently, three non-vitamin K antagonist oral anticoagulants or directly acting oral anticoagulants have been registered in the Russia, which in large randomized clinical trials (RCTs) were compared with warfarin in the prevention of stroke and systemic embolism. The present article analyzes the data of RCTs, postmarketing studies of oral anticoagulants, and presents groups of patients for whom these drugs are preferred. The choice of oral anticoagulants for the prevention of stroke in the following subgroups of patients with atrial fibrillation is discussed: patients with one stroke risk factor (CHA2DS2VASc1 in men or 2 in women), patients of different age groups, patients with concomitant coronary artery disease/acute coronary syndrome, a history of stroke, patients with chronic kidney disease, patients with a high risk of gastrointestinal bleeding, and a group of patients with concomitant arterial hypertension and chronic heart failure. We compared the efficacy and safety of oral non-vitamin K antagonist oral anticoagulants or directly acting oral anticoagulants with vitamin K antagonists in patients with non-valvular atrial fibrillation.

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