Combination Of Oral Anticoagulants Research Articles

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Antithrombotic management in atrial fibrillation patients following percutaneous coronary intervention: A clinical review.

Patients with atrial fibrillation (AF) often develop acute coronary syndrome and undergo percutaneous coronary intervention (PCI), and vice versa. Acute coronary syndrome and PCI mandate the use of dual antiplatelet therapy, while oral anticoagulation is recommended in patients with AF to mitigate thromboembolic risks. Clinical evidence concerning antithrombotic treatment in patients with AF and PCI has been accumulated, but when combined, the therapeutic strategy becomes complex. Although triple therapy, a combination of oral anticoagulation with dual antiplatelet therapy, has been used for patients with AF undergoing PCI as an initial antithrombotic strategy, less intensive regimens may be associated with a lower rate of bleeding without an increased risk in thrombotic events. This narrative review article summarizes currently available evidence of antithrombotic therapy in patients with AF undergoing PCI.

Antithrombotic therapy in patients after transcatheter aortic valve implantation: a network meta-analysis.

The optimal antithrombotic therapy to balance the risk of thrombosis and bleeding in patients who undergo transcatheter aortic valve implantation (TAVI) is unknown. This systematic review/network meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of different oral anticoagulant (OAC) and antiplatelet regimens in patients post-TAVI. MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to April 2023. Co-primary outcomes were all-cause death and major bleeding. We conducted Bayesian network meta-analyses to compare all interventions simultaneously. For each outcome, we generated odds ratios (ORs) with 95% credible intervals using a random-effects model with informative priors, and ranked interventions based on mean surface under the cumulative ranking curve. We included 11 RCTs (n=6415), including 1 unpublished RCT. Three trials enrolled patients with an indication for an OAC. Overall risk of bias was low or with some concerns. Median age was 81 years. Median follow-up was 6 months. The combination of OAC plus single antiplatelet therapy (SAPT) increased the risk of all-cause death compared with dual antiplatelet therapy (DAPT) (OR 1.78, 95% credible interval 1.15-2.77). No other comparisons for all-cause death were significantly different. For major bleeding, SAPT reduced the risk compared with DAPT, direct-acting OAC, and OAC+SAPT (OR 0.20-0.40), and DAPT reduced the risk compared with OAC+SAPT. SAPT and DAPT ranked best for all-cause death, while SAPT ranked best for major bleeding. In post-TAVI patients, SAPT may provide the optimal balance of reducing thrombotic events while minimizing the risk of bleeding.

Bleeding and thrombotic risk of different antiplatelet regimens posttranscatheter edge-to-edge mitral valve repair in patients with an indication for oral anticoagulation: Results from an all-comers national registry.

Evidence-based recommendations for antithrombotic treatment in patients who have an indication for oral anticoagulation (OAC) after transcatheter edge-to-edge mitral valve repair (TEER) are lacking. To compare bleeding and thrombotic risk for different antithrombotic regimens post-TEER with MitraClip in an unselected population with the need for OACs. Bleeding and thrombotic complications (stroke and myocardial infarction) up to 3 months after TEER with mitraclip were evaluated in 322 consecutive pts with an indication for OACs. These endpoints were defined by the Mitral Valve Academic Research Consortium criteria and were compared between two antithrombotic regimens: single antithrombotic therapy with OAC (single ATT) and double/triple ATT with a combination of OAC and aspirin and/or clopidogrel (combined ATT). Collectively, 108 (34%) patients received single ATT, 203 (63%) received double ATT and 11 (3%) received triple ATT. Bleeding events occurred in 67 patients (20.9%), with access site related events being the most frequent cause (37%). Bleeding complications were observed more frequently in the combined ATT group than in the single ATT group: 24% versus 14% [p = 0.03, adjusted RR: 0.55 (0.3-0.98)]. Within the combined group, the bleeding risk was 23% in the double ATT and 45% in the triple ATT group. Thrombotic complications occurred in only three patients (0.9%), and all belonged to the combined ATT group. In patients with an indication for OACs, withholding of antiplatelet therapy post-TEER with Mitraclip was associated with a 45% reduction in bleeding and without a signal of increased thrombotic risk.

Combined pharmacotherapy in atrial fibrillation patients and their risk of stroke, dementia, and cardiovascular deaths

Abstract Background Even though there have been many advances in oral anticoagulation (OAC) for stroke prevention among atrial fibrillation (AF) patients, the incidence of adverse outcomes in these patients remain high. Optimal management of underlying cardiovascular (CV) conditions have been proposed to provide additional benefit to the prognosis of AF, including major CV and cognitive outcomes. However, concrete epidemiological evidence is still lacking. Purposes To investigate the effect of combinations of CV pharmacotherapies on the risk of stroke, dementia, and CV deaths among AF patients. Methods Using the Swedish Total Population Register and National Patient Register, we identified all individuals born between 1907-1950, who have been living in Sweden since 1987 and were diagnosed with first-ever AF between January 1st 2006-December 31st 2010. Persons with a history of stroke and dementia at the time of AF diagnoses were excluded. Included AF patients were followed for stroke, dementia, and cardiovascular deaths until December 31st, 2020. Use of CV drugs (i.e., OAC, antihypertensives, antiplatelets, and lipid-lowering drugs (LLD)) was defined as prescription within 1 year since AF diagnosis, ascertained via the Prescribed Drug Register. Results A total of 135896 AF patients were followed for a mean follow-up of 6.8 years (SD 4.8), and 17259 (12.7%) incident stroke, 18092 (13.3%) dementia, and 75514 (55.6%) CV deaths were observed. OAC were prescribed to 41.53% of the AF patients within 1 year since AF diagnosis, and antihypertensives to 80.6%, LLD to 30.8%, and antiplatelets to 45.4%. only 2.8% of the AF patients were using OAC only, and 38.7% were using both OAC and antihypertensives. 10.9% were using both OAC and antiplatelets, and 16.8% both OAC and LLD. After propensity score matching, combination of OAC and antihypertensives was statistically significantly associated with a lower risk of stroke (multi-adjusted hazard ratio [HR]=0.80, 95% confidence interval [CI]: 0.93-0.88) and CV deaths (0.84, 0.80-0.88), although insignificant for dementia (0.93, 0.85-1.02), compared to using only OAC. OAC combined with antiplatelets, and OAC with LLD, were however associated with an increased risk of stroke and dementia (HR ranging from 1.08-1.23), but a decreased risk of CV deaths (HR=0.96, 95% CI: 0.93-0.98; HR=0.82, 95% CI: 0.80-0.85), compared to using only OAC. Using neither drug in the combinations was associated with the highest risk for all three outcomes. Conclusions This observational study indicates that older AF patients may benefit from combined therapy of OAC and antihypertensives in terms of stroke, CV deaths, and dementia. Further evidence from clinical trials is needed to confirm this finding.

Antithrombotic therapy after angioplasty of pulmonary vein stenosis due to atrial fibrillation ablation: A two-center experience and review of the literature.

Pulmonary vein stenosis (PVS) is a severe complication of atrial fibrillation (AF) ablation resulting in narrowing of affected pulmonary veins (PVs). Interventional treatment consists of angioplasty with or without PV stenting. The optimal postprocedural antithrombotic therapy is not known. To investigate the impact of antithrombotic medical therapy on recurrence of PVS after PV angioplasty. A retrospective study of patients undergoing PV angioplasty with or without stent implantation in two German centers was performed. Postinterventional antithrombotic therapy consisted of either dual antiplatelet therapy (DAPT) or a combination of oral anticoagulation with single or dual antiplatelet therapy for 3-12months after intervention. Angiographic follow-up was recommended 3, 6, and 12months after intervention and in case of symptom recurrence. Thirty patients underwent treatment of 42 PVS. After intervention, twenty-eight patients received triple therapy and 14 patients received dual therapy/DAPT; restenosis occurred in 5/22 (22.7%) patients with triple therapy and 8/14 (57.1%) patients with dual therapy/DAPT PV (p= .001). Estimated freedom from PV restenosis after 500 days was 18.8 ± 15.8% (dual therapy/DAPT) and 76.2 ± 10.5% (triple therapy) (p= .003). Univariate regression analysis revealed postprocedural medication as a significant risk factor for restenosis (p= .019). No bleeding events occurred regardless of applied antithrombotic therapy. Triple antithrombotic therapy after PV angioplasty is associated with less frequent restenosis as compared to dual antiplatelet therapy or a combination of anticoagulation and single antiplatelet therapy. No severe bleeding events occurred in patients on triple therapy. These findings need to be confirmed in larger patient cohorts.

A Tailored Antithrombotic Approach for Patients with Atrial Fibrillation Presenting with Acute Coronary Syndrome and/or Undergoing PCI: A Case Series.

The combination of oral anticoagulants (OAC) and dual antiplatelet therapy (DAPT) is the mainstay for the treatment of patients with atrial fibrillation (AF) presenting with acute coronary syndrome (ACS) and/or undergoing PCI. However, this treatment leads to a significant increase in risk of bleeding. In most cases, according to the most recent guidelines, triple antithrombotic therapy (TAT) consisting of OAC and DAPT, typically aspirin and clopidogrel, should be limited to one week after ACS and/or PCI (default strategy). On the other hand, in patients with a high ischemic risk (i.e., stent thrombosis) and without increased risk of bleeding, TAT should be continued for up to one month. Direct oral anticoagulants (DOAC) in triple or dual antithrombotic therapy (OAC and P2Y12 inhibitor) should be favored over vitamin K antagonists (VKA) because of their favorable risk/benefit profile. The choice of the duration of TAT (one week or one month) depends on a case-by-case evaluation of a whole series of hemorrhagic or ischemic risk factors for each patient. Likewise, the specific DOAC treatment should be selected according to the clinical characteristics of each patient. We propose a series of paradigmatic clinical cases to illustrate the decision-making work-up in clinical practice.

Clopidogrel or ticagrelor alongside dabigatran in acute coronary syndrome and indication for NOAC: a study rationale.

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non-vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition. Trial registration number: NL75644.096.21.

Characteristics and antithrombotic treatment patterns of patients with concomitant coronary artery disease and atrial fibrillation from Thailand\u2019s COOL-AF registry

BackgroundConcomitant coronary artery disease (CAD) and atrial fibrillation (AF) are common in clinical practice. The aim of this study was to investigate the characteristics and antithrombotic treatment patterns of patients with concomitant CAD and AF from the COhort of antithrombotic use and Optimal INR Level in patients with non-valvular atrial fibrillation in Thailand (COOL-AF Thailand) registry.MethodsRegistry enrollment criteria included patients aged ≥ 18 years who were diagnosed with AF for any duration at any of 27 public hospitals located across Thailand during 2014–2017. The That Clinical Trials Registry study registration number is TCTR20160113002. Statistical comparisons of characteristics and treatment strategies were performed between patients with and without CAD.ResultsOf a total of 3461 AF patients, 557 had concomitant CAD (16.1%). Patients with concomitant CAD and AF were significantly older, more likely to be male, had more comorbidities, and had more cardiovascular implantable electronic devices. History of stroke/transient ischemic attack and prior bleeding was not significantly different between groups. CHA2DS2-VASc score and HAS-BLED score were both higher in patients with CAD than in patients without CAD (4.17 vs. 2.78, p < 0.001, and 2.01 vs. 1.45, p < 0.001, respectively). Utilization of oral anticoagulant was less in patients with CAD (76.0% vs. 84.3%, p < 0.001). Concomitant use of antiplatelet was found to be a major cause of oral anticoagulant (OAC) underutilization. Specifically, the rate of OAC prescription was 95.9% in patients without antiplatelet, and 43.7% in patients with antiplatelet. Among patients with CAD who were on OAC, the rate of concomitant antiplatelet prescription was still high. In this group, 63% of patients were on triple therapy when percutaneous coronary intervention (PCI) with drug eluting stent was performed within 1 year, and 32.2% of patients without prior PCI or acute coronary syndrome were taking at least one antiplatelet with OAC.ConclusionAmong patients with concomitant CAD and AF, physicians were reluctant to discontinue antiplatelet. The use of antiplatelet discourages physicians from prescribing OAC. Underutilization of OAC may increase the risk of ischemic stroke, and an inappropriate combination of OAC and antiplatelet may increase the risk of bleeding.Trial registration The trial has been registered with the Thai Clinical Trials Registry (TCTR) which complied with WHO International Clinical Trials Registry Platform dataset. The Registration Number is TCTR20160113002 (05/01/2016).

Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non-vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y12 inhibitor, preferably clopidogrel, in combination with a non-vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone.

Abstract 14344: Prognostic Factors of Atrial Fibrillation Patients With Coronary Artery Disease: The Fushimi Af Registry

Background: Atrial fibrillation (AF) patients are likely to have concomitant coronary artery disease (CAD). A new strategy of antithrombotic therapy in AF patients with stable CAD was demonstrated in recent randomized clinical trials. Now that antithrombotic therapy for AF patients with CAD has reached a major turning point, it is important to know the prognostic factors in those patients. Purpose: In this study, we investigated clinical characteristics, cardiovascular events and prognostic factors in AF patients with CAD. Methods: The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow up data including prescription status were available in 4,441 patients from March 2011 to November 2019. Of 4,441 patients, 645 patients had a history of CAD at enrollment. Results: The mean age was 76.4±8.6 and 65.9% were male. Averages of CHA 2 DS 2 -VASc score and HAS-BLED score were 4.41 and 2.35, respectively. Oral anticoagulant (OAC) was prescribed in 52.9% of those patients and antiplatelet drug (APD) was prescribed in 70.4%. The combination of OAC and APD was prescribed in 36.0%. During follow-up period (median 1,495 days), cardiac death occurred in 51 patients, composite of cardiac death, myocardial infarction (MI) and stroke in 136, and major bleeding in 77 (1.8, 5.1 and 2.9 per 100 person-years, respectively). In multivariate analysis, factors associated with composite of cardiac death, MI and stroke in AF patients with CAD were low body weight (&lt;=50kg) (hazard ratio [95% confidence interval]; 1.62 [1.07-2.47]), previous stroke (1.69 [1.13-2.52]), heart failure (1.47 [1.02-2.11]), hypertension (0.60 [0.41-0.87]) and diabetes mellitus (1.62 [1.13-2.32]). Furthermore, factors associated with major bleeding in AF patients with CAD were anemia (male: hemoglobin&lt;12 g/dl, female: hemoglobin&lt;11 g/dl) (1.82 [1.09-3.04]) and thrombocytopenia (&lt;150,000 /μL) (3.02 [1.29-7.03]). Conclusion: In Japanese AF patients with CAD, low body weight, previous stroke, heart failure, hypertension and diabetes mellitus were associated with cardiovascular events, and anemia and thrombocytopenia were associated with major bleeding.

Combination of Oral Anticoagulants and Single Antiplatelets versus Triple Therapy in Nonvalvular Atrial Fibrillation and Acute Coronary Syndrome: Stroke Prevention among Asians.

Atrial fibrillation (AF), the most prevalent arrhythmic disease, tends to foster thrombus formation due to hemodynamic disturbances, leading to severe disabling and even fatal thromboembolic diseases. Meanwhile, patients with AF may also present with acute coronary syndrome (ACS) and coronary artery disease (CAD) requiring stenting, which creates a clinical dilemma considering that majority of such patients will likely receive oral anticoagulants (OACs) for stroke prevention and require additional double antiplatelet treatment (DAPT) to reduce recurrent cardiac events and in-stent thrombosis. In such cases, the gentle balance between bleeding risk and atherothromboembolic events needs to be carefully considered. Studies have shown that congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, and previous stroke or transient ischemic attack (TIA; doubled)-vascular disease, age 65 to 74 years, sex category (female; CHA 2 DS 2 -VASc) scores outperform other scoring systems in Asian populations and that the hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly (>65 years), drugs/alcohol concomitantly (1 point each; HAS-BLED) score, a simple clinical score that predicts bleeding risk in patients with AF, particularly among Asians, performs better than other bleeding scores. A high HAS-BLED score should not be used to rule out OAC treatment but should instead prompt clinicians to address correctable risk factors. Therefore, the current review attempted to analyze available data from patients with nonvalvular AF who underwent stenting for ACS or CAD and elaborate on the direct-acting oral anticoagulant (DOAC) and antiplatelet management among such patients. For majority of the patients, "triple therapy" comprising OAC, aspirin, and clopidogrel should be considered for 1 to 6 months following ACS. However, the optimal duration for "triple therapy" would depend on the patient's ischemic and bleeding risks, with DOACs being obviously safer than vitamin-K antagonists.

Antithrombotic therapy after TAVI.

The combination of oral anticoagulation and the antiplatelet drug clopidogrel increases the risk of bleeding after transcatheter aortic valve implantation (TAVI) compared with oral anticoagulation alone, according to the results of the POPular TAVI trial cohort B.

Double Antithrombotic versus Triple Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome.

In atrial fibrillation (AF), oral anticoagulant (OAC) therapy with either vitamin K antagonist or non-vitamin K antagonist is used to prevent thromboembolic complications. In patients who presented with acute coronary syndrome (ACS) and were treated by percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 inhibitor reduces major adverse cardiac events (MACEs) and stent thrombosis. Consequently, in patients with AF who presented with ACS and were treated by PCI, the combination of OAC and DAPT, the so-called triple antithrombotic therapy (TAT) is needed to improve the outcome of the patients. However, the use of TAT increases the risk of bleeding. Several randomized clinical trials and a meta-analysis evaluated the use of TAT and double antithrombotic therapy (DAT) in this population, and DAT is defined as patients who receive combination of one antiplatelet and OAC. In general, the studies demonstrated a reduction in bleeding event in patients who received DAT as compared with TAT, with similar incidence of thromboembolic complications and MACE. To date, there is no established consensus or guideline for the most appropriate combination of antithrombotic agents in patients with AF and ACS who undergo PCI. Tailoring the treatment for each individual is likely the best approach to determine the balance of bleeding risk and ischemic events before starting antithrombotic therapy. Future trials with adequate sample size are needed to find the most appropriate combination of antiplatelet and OAC in patients with AF who presented with ACS and treated by PCI.

Bleeding and ischaemic outcomes in patients treated with dual or triple antithrombotic therapy: systematic review and meta-analysis.

The combination of oral anticoagulation with a P2Y12 inhibitor and aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is associated with a high bleeding risk. Dual antithrombotic therapy (DAT) with omission of aspirin is a promising option to reduce bleedings, but carries a yet unknown risk of ischaemic events. We therefore sought to systematically review and analyse randomized controlled trials investigating DAT vs. triple antithrombotic therapy (TAT) in patients with AF following PCI and/or acute coronary syndrome (ACS). We included four trials with overall 9317 patients (5039 DAT, 4278 TAT) in our analysis. Dual antithrombotic therapy was associated with a significant reduction in thrombolysis in myocardial infarction major bleeding [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.42-0.65; P = 0.0001], while the composite trial-defined ischaemic endpoint did not differ significantly between DAT and TAT (HR 0.98, 95% CI 0.79-1.22; P = 0.88). There was also no difference regarding the occurrence of myocardial infarction (MI; HR 1.16, 95% CI 0.92-1.46; P = 0.21) or stent thrombosis (HR 1.25, 95% CI 0.69-2.26; P = 0.46). Absolute numbers for MI were 131/4278 (3.1%) with TAT and 182/5039 (3.6%) with DAT, and for stent thrombosis 32/4278 (0.75%) and 52/5039 (1%), respectively. A post hoc power calculation based on the size and event rate of this meta-analysis revealed 80% power to detect a 37% and 100% increase in MI and stent thrombosis, respectively. Dual antithrombotic therapy significantly reduces bleedings compared with TAT and seems to have a similar effect in preventing ischaemic endpoints in AF patients post-PCI or ACS. Future investigations are needed to determine its applicability specifically in patients at high risk of ischaemic outcomes.

Antiplatelet therapy: new insights on the secondary prevention of stroke

Antiplatelet agents represent an important part of the therapeutic armamentarium in the prevention of stroke. Among them, aspirin is the gold standard but its chronic use has been associated with gastric intolerance, gastrointestinal and systemic hemorrhages and drug-resistance. Triflusal is a new antiplatelet agent from the family of salicylates but is not derived from aspirin and has a more selective mechanism of action : inhibition of thromboxane A2 in the platelet with no effect on prostacyclin biosynthesis in the endothelium. In the quest for the search of new antiplatelet agents, triflusal has shown a similar relative risk reduction than aspirin for the prevention of stroke but with reduced severe hemorrhagic side effects. The efficacy and better safety profile of triflusal vs aspirin in the secondary prevention of stroke has been demonstrated in major, randomized and double blind clinical trials and confirmed after a long term study with a mean follow up of 17 years, as well as in a Cochrane meta-analysis. Aspirin, but not triflusal, increased antihypertensive therapy requirements during long term treatment in the secondary prevention of stroke. In patients with atrial fibrillation, the combination of oral anticoagulants with triflusal has shown increased efficacy versus the standard oral single anticoagulation treatment with no increase of haemorrhagic risk. Studies have shown that the risk of upper gastrointestinal bleeding associated with the use of triflusal was negligible whereas the hemorrhagic risk associated with the use of aspirin, including low doses aspirin, was evident. Triflusal was well tolerated in asthmatic patients with aspirin-exacerbated –respiratory-diseases. The efficacy of triflusal in secondary prevention of stroke and its better safety profile when compared to aspirin has been recognized in important International Guidelines including the European Stroke Organization Guidelines.

Time in therapeutic range and major adverse outcomes in atrial fibrillation patients undergoing percutaneous coronary intervention: The Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) registry

Combination of oral anticoagulation (OAC) and antiplatelets is used in atrial fibrillation (AF) patients undergoing percutaneous coronary intervention and stent (PCI-S) procedure but is associated with increased bleeding when triple antithrombotic therapy (TAT) is used. Our aim was to analyze the impact of time in therapeutic range (TTR) on outcomes, in patients prescribed with TAT. Ancillary analysis from the AFCAS registry in patients assigned to TAT. TTR was calculated with Rosendaal method. Outcomes were analyzed according to TTR tertiles (T1 [≤56.8%] vs. T2 [56.9-93.8%] vs. T3 [≥93.9%]). Major bleeding was the primary outcome. Of 963 patients enrolled, 470(48.8%) were prescribed with TAT at discharge and qualified for this analysis. Median [IQR] TTR was 80.0% [45.3-100%]. After 359 [341-370] days, major bleeding rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3: 10.3% vs. 4.7% vs. 2.3%, P=.006). Kaplan-Meier analysis demonstrated a progressively lower risk for major bleeding across tertiles (P=.006). Patients in the highest TTR tertile had a non-significant lower risk for major adverse coronary and cerebrovascular events (MACCE) (log-rank: 4.905, P=.086). Cox regression analysis showed that T2 and T3 were inversely associated with major bleeding (hazard ratio [HR]:0.39, P=.050 and HR: 0.21, P=.005). Continuous TTR was inversely associated with major bleeding (HR: 0.98, P<.001). For MACCE, adjusted Cox analysis found a non-significant lower risk for T3 (HR: 0.64, P=.128). In AF patients undergoing PCI-S prescribed TAT, good quality anticoagulation control (as reflected by TTR) was closely related to bleeding outcomes during follow-up. Despite some suggestive trends for an inverse relationship between TTR and MACCE, no definitive conclusions can be drawn, and further large studies are needed.

Safety and efficacy of anti-thrombotic regimens in patients with percutaneous coronary intervention requiring oral anticoagulation: A traditional and network meta-analysis.

Previous reports have been inconsistent in generating a consensus for optimal treatment strategy for patients with percutaneous coronary intervention (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and network meta-analysis to evaluate the safety and efficacy of anti-thrombotic regimens in this subset of patients. 30 articles were recovered through preferred reporting items for systematic reviews and meta-analyses (PRISMA) using MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) from inception to December 2016. Dual antiplatelet therapy (DAPT) was found to be the safest treatment modality when compared to triple therapy (TT) or combination of OAC and single antiplatelet agent (OAC+SAP) [Major bleeding: (DAPT vs OAC+SAP: odds ratio (OR), 0.53; 95% credible interval (CrI), 0.30-0.91) (DAPT vs TT: OR, 0.45; 95% CrI, 0.31-0.64)]. There were no significant differences in major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular (CV) or total survival, stent thrombosis or target vessel revascularization (TVR) amongst the three treatment arms. TT was ranked superior for stroke reduction (SUCRA, 69%) followed by OAC+SAP and DAPT. When traditional analysis was adjusted for randomized data, OAC+SAP was equivalent to TT with regards to stroke (OR, 0.74; 95% confidence interval (CI), 0.38-1.46; p=0.39) and showed significant reduction in MACE and total mortality. DAPT was found to be the safest and equally effective regimen when compared to TT and OAC+SAP. However this strategy bears considerable risk to patients with high thromboembolic risk. This issue can be encountered by using OAC+SAP as an alternative of TT in patients with intermediate to high stroke risk and intermediate to high bleeding propensity.

Abstract 12011: Time in Therapeutic Range and Major Adverse Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention on Triple Antithrombotic Therapy: The Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) Registry

Introduction: Combination of oral anticoagulation (OAC) and antiplatelet therapy is used in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention stent (PCI-S) implantation but is associated with increased bleeding, especially if triple antithrombotic therapy (TAT) is used. Hypothesis: Adverse outcomes in patients prescribed with TAT after a PCI-S are related to quality of anticoagulation control as reflected by time in therapeutic range (TTR). Methods: Subgroup analysis from the AFCAS registry in patients assigned to TAT at discharge. TTR was calculated using Rosendaal method. Outcomes were determined for TTR tertiles (T1:&lt;56.8%, T2:56.9-93.8%, T3:&gt;93.9%). Results: Of 963 patients originally enrolled, 470 (48.8%) were prescribed TAT at discharge and had all data available for this analysis. Median [IQR] TTR was 80.0% [45.3-100%]. After a mean±SD follow-up of 343±94 days, crude major bleeding rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3: 10.3% vs. 4.7% vs. 2.3%, p=0.006). Kaplan Meier survival analysis demonstrated a progressively lower risk for major bleeding across TTR tertiles (p=0.006; Figure). Patients in the highest TTR tertile (T3) had a lower risk for major adverse coronary and cerebrovascular events (MACCE) compared to those in T1 and T2 (Log-Rank:4.420, p=0.036). On Cox regression analysis (adjusted for age, gender, AF type, CHA 2 DS 2 -VASc, PCI-S indication/setting), T2 and T3 were inversely associated with major bleeding (HR:0.39, 95%CI:0.15-1.00, p=0.050 and HR:0.21, 95%CI:0.07-0.63, p=0.005). Continuous TTR was also inversely associated with major bleeding (HR:0.98, 95%CI:0.97-0.99, p&lt;0.001). Patients in T3 had the lowest risk of MACCE (HR:0.58, 95%CI:0.35-0.96, p=0.033). Conclusions: In AF patients undergoing a PCI-S prescribed TAT, good quality anticoagulation control (as reflected by TTR) is related to better cardiovascular and bleeding outcomes during follow-up.

Optimal antithrombotic treatment in patients with atrial fibrillation and coronary stents: an update.

The optimal antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is still debated. This review is an update of a previous review and aims to summarize new published data regarding the management of this group of atrial fibrillation patients. Recent data report an underuse of oral anticoagulation in patients with atrial fibrillation undergoing PCI while indicated. However, tools for risk assessment and thus better guidance for decision-making are lacking, especially for elderly atrial fibrillation patients. New evidence suggests that the combination of oral anticoagulation and clopidogrel without aspirin may improve clinical outcomes in comparison with triple therapy; however, there is little data regarding the role of non-vitamin K oral anticoagulants and newer P2Y12 inhibitors in these regimens. Despite accumulating data on the assessment of bleeding and thrombotic risk, the management of elderly atrial fibrillation patients, new treatment regimens, and the role of more potent antithrombotic agents, the optimal antithrombotic therapy for patients with atrial fibrillation after PCI is still unclear. In the meantime, careful assessment of both thrombotic and bleeding risk and individualized decision-making are paramount to ensure the best patient outcomes.