Dual Antithrombotic Therapy Research Articles

Triple or Dual Antithrombotic Therapy After PCI (TRIDUAL-PCI) Coronary Intervention in Patients With Non-valvular Atrial Fibrillation. Real-world Italian Multicenter Registry (TRIDUAL-PCI)

Triple or Dual Antithrombotic Therapy After PCI (TRIDUAL-PCI) Coronary Intervention in Patients With Non-valvular Atrial Fibrillation. Real-world Italian Multicenter Registry (TRIDUAL-PCI)

Direct-acting Anticoagulants in Chronic Coronary Syndromes

Direct-acting oral anticoagulants (DOACs) are easier to use, safer than and as effective as vitamin K antagonists (VKA) in the treatment of non-valvular AF (NVAF). Because of their favourable safety profile and easier use than VKAs, DOACs as anti-thrombotic therapy may have a role in the management of chronic coronary syndromes (CCS). To date, few studies have evaluated DOACs in this setting. Initial studies have focused on patients receiving DOACs for NVAF undergoing acute or elective percutaneous coronary intervention who additionally require dual antiplatelet therapy (DAPT). Rivaroxaban 15 mg once daily plus a P2Y12 inhibitor compared with a VKA regimen was associated with a reduction of bleedings (HR 0.59; 95% CI [0.47–0.76]; p<0.001). Rivaroxaban 2.5 mg twice daily plus DAPT up to 12 months followed by rivaroxaban 15 mg once daily plus P2Y12 inhibitor showed similar results. Dabigatran 110 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen was associated with a reduction of bleedings (HR 0.52; 95% CI [0.42–0.63]; p<0.001), after a mean follow-up of 14 months. A dabigatran 150 mg regimen showed similar results. Apixaban 5 mg twice daily plus a P2Y12 inhibitor versus a VKA regimen confirmed at 6 months the safety of DOACs with a reduction of bleedings (HR 0.69; 95% CI [0.58–0.81]; p<0.001 for non-inferiority and superiority). Edoxaban 60 mg once daily plus a P2Y12 inhibitor was non-inferior to a VKA regimen on bleeding outcomes (major bleeding or non-major clinically relevant non-major bleeding) after a 12-month follow-up (HR 0.83; 95% CI [0.65–1.05]; p=0.001 for non-inferiority; p=0.1154 for superiority). Meta-analysis of these four trials confirmed the safety of DOACs regarding bleeding outcomes, but showed a trend toward stent thrombosis for dual antithrombotic therapy using DOACs versus triple antithrombotic therapy using VKAs. DOACs may show promise in the management of high-risk patients with chronic coronary syndromes. In these patients, rivaroxaban 2.5 mg twice daily in addition to aspirin was shown to reduce the composite outcome of cardiovascular death, stroke or MI compared to aspirin alone (HR 0.76; 95% CI [0.66–0.86]; p<0.001). All-cause death, cardiovascular death and stroke were also significantly lower. This benefit was at the cost of an increase in non-fatal bleeding.

Antithrombotic agents for primary and secondary prevention of cardiovascular events in patients with end-stage renal disease on chronic hemodialysis

Background and aimsCardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD. MethodsIn a cross-sectional population based cohort of chronic HD patients (n = 626) from Vienna, Austria, the medical histories of patients and use of antithrombotic treatment were recorded, and the distribution of antithrombotic therapies for primary (n = 260, 41.5%) or secondary (n = 366, 58.5%) prevention of CVD was analyzed. ResultsSingle antiplatelet therapy (SAPT) was used in 234 patients (37.4%), dual antiplatelet (DAPT) in 50 (8.0%), combination of anticoagulation and antiplatelet in 59 (9.4%), anticoagulation monotherapy in 78 (12.5%), and no antithrombotics in 205 patients (32.7%). The prevalence of CVD was 58.5%. In primary CVD prevention, 23.5% (n = 61) of patients were treated with SAPT. For secondary prevention, SAPT was used in 173 (47.3%), DAPT in 49 (13.4%), and dual antithrombotic therapies in 50 patients (13.7%), while 55 (15.0%) patients received no antithrombotics. Age (odds ratio [OR] per 1 year increase 0.96, 95%CI 0.94–0.99, p = 0.004) and hereditary nephropathy (OR 4.13, 95%CI 1.08–15.78, p = 0.038) were independently associated with the absence of antithrombotic therapy in secondary CVD prevention. ConclusionThe majority of patients did not receive antithrombotic therapy for primary prevention. Only 15% did not receive antithrombotic agents in the secondary prevention setting. The net-clinical benefit of antithrombotic therapy in ESRD needs to be determined.

Pharmacological strategy pre- and post-percutaneous coronary intervention in patients with acute coronary syndrome on oral anticoagulation therapy

In patients with atrial fibrillation (AF) who undergo an acute coronary syndrome (ACS), with or without percutaneous coronary intervention and coronary stent implantation, the association of dual antiplatelet therapy with an oral anticoagulant (also known as triple antithrombotic therapy, TAT) increases the risk for major and fatal bleeding. Recently, several trials have evaluated alternative therapeutic regimens to TAT, such as dual antithrombotic therapy (DAT) comprising a direct oral anticoagulant and a platelet P2Y12 receptor inhibitor. In the context of patients treated with percutaneous coronary intervention, these regimens have generally been associated with a reduction in bleeding that was not accompanied by a substantial increase in ischemic events. However, the net benefit of DAT is more controversial in the case of patients at higher thrombotic risk, such as patients with ACS. This review, based on the available literature, describes the best peri-procedural and post-procedural antithrombotic strategies for patients with AF and ACS.

Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients.

To assess the efficacy-safety profile of dual antithrombotic therapy (DAT) including direct oral anticoagulant (DOAC) vs. triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Randomized trials of AF patients with ACS/PCI, comparing DAT using DOACs against TAT, were selected. Overall, 11161 studies were screened, 458 trials assessed, and four included, comprising 10234 patients followed for a mean of 11 months. DAT compared to TAT resulted in significant reductions of trial-defined primary safety outcome [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.50-0.79, number needed to treat (NNT) 17] and of thrombolysis in myocardial infarction (TIMI) major bleeding (OR 0.54, 95% CI 0.41-0.70, NNT 76) and in a numerical reduction of intracranial haemorrhage (OR 0.50, 95% CI 0.21-1.19, NNT 314), which became significant after exclusion of DOACs from TAT and vitamin K antagonist from DAT arms (OR 0.31, 95% CI 0.15-0.64). There were no significant differences in the risks of cardiovascular or any deaths or stroke, but with DAT, there was a numerical increase in myocardial infarctions (MIs) (OR 1.23, 95% CI 0.99-1.54, estimated NNT for an additional harmful outcome (NNTH) 151), which became significant in the ACS/PCI subgroup (OR 1.43, 95% CI 1.02-2.00), and a 60% significant increase in stent thrombosis risk (OR 1.60, 95% CI 1.02-2.52; NNTH 274). Dual antithrombotic therapy, compared to TAT, conferred a significantly reduced risk of overall bleeding but with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup.

Safety and efficacy of dual versus triple antithrombotic therapy in Patients with atrial fibrillation undergoing percutaneous coronary intervention: A meta-analysis.

ABSTRACTBackground:Patients with atrial fibrillation undergoing percutaneous coronary intervention have indications for oral anticoagulation and dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor. The concurrent use of all three agents, termed triple oral antithrombotic therapy (TAT), increases the risk of bleeding. A number of prospective trials showed that the omission of aspirin mitigates the risk of bleeding without affecting major adverse cardiovascular event (MACE).Materials and Methods:The databases of PubMed, Embase, and Cochrane Central databases were searched from inception to October 2019. Relevant randomized control trials comparing dual antithrombotic therapy (DAT) versus TAT were identified and a metanalysis was performed using random-effect model. The safety endpoints of interest were thrombolysis in myocardial infarction criteria (TIMI) major and minor bleeding, TIMI major bleeding, and intracranial bleeding. The efficacy endpoints of interest were MACE and individual components of MACE.Results:Six trials with 11,722 patients were included. For safety endpoint, DAT was associated with significantly lower incidence of TIMI major and minor bleeding [RR: 0.58, 95% CI 0.44–0.77, P = 0.0001], TIMI major bleeding [RR: 0.55, 95% CI 0.42–0.73, P < 0.0001] as well as intracranial bleeding [RR: 0.35, 95% CI 0.16–0.73, P = 0.006] compared with TAT. No significant difference was observed for MACE [RR: 0.96 (0.79–1.17) P = 0.71] or any of the individual components of MACE between the two groups.Conclusion:Omission of aspirin from TAT in patients with Atrial Fibrillation (AF) after percutaneous coronary intervention is associated with lower risk of bleeding without compromising the efficacy in terms of mortality and cardiovascular thrombotic events.

Modern strategy to improve remote results of surgical treatment of peripheral artery disease

Treatment of patients presenting with peripheral artery disease requires a comprehensive approach: correction of risk factors, drug therapy and, if necessary, an endovascular/hybrid/open intervention. Reconstructive operation may effectively improve a patient's quality of life in intermittent claudication, save the limb and life in case of severe ischaemia. Discussed in the article are advantages and disadvantages of various types of surgical interventions for peripheral artery disease, the concept PLAN (Patient risk, Limb severity, and ANatomic complexity) and the new Global Anatomic Staging System (GLASS). Good remote results may be ensured by adequate medicamentous therapy. Variations of antithrombotic therapy are versatile and debatable. Long-term dual antithrombotic or systemic anticoagulant therapy with administration of vitamin K antagonists are not indicated for peripheral artery disease. In this connection, the findings of the COMPASS and VOYAGER PAD studies are analysed. The VOYAGER PAD trial showed that in patients with peripheral artery disease who underwent revascularization of lower limbs, the addition of rivaroxaban at a dose of 2.5 mg twice daily to aspirin decreased the risk of lower-extremity unfavourable ischaemic events and major adverse cardiovascular events by 15%. The obtained findings open new possibilities of conservative therapy having a significant role in decreasing the risk for development of limb-threatening conditions.

Coronary artery bypass grafting in myocardial infarction and unstable angina pectoris: analysis of perioperative factors. Part 1

The purpose of this study was to assess the perioperative clinical, demographic and anatomo-angiographic factors in patients presenting with non-ST-segment elevation acute coronary syndrome and being candidates for coronary artery bypass grafting, depending on the presence or absence of myocardial infarction. Over the period from 2017 to 2018 within the framework of a single-centre register, the study enrolled a total of 166 consecutive patients admitted with non-ST segment elevation acute coronary syndrome and recommended by the cardiosurgical team to undergo coronary artery bypass grafting. Depending on the outcome of acute coronary syndrome, the patients were divided into 2 groups: Group One included 98 (59%) patients with unstable angina pectoris and Group Two comprised 68 (41%) patients with myocardial infarction. A lethal outcome occurred in 2 (3%) Group Two patients prior to revascularization, hence they were not included into the analysis comparing the results of surgery in both groups, however these data were taken into consideration, being analysed separately. The group of patients with myocardial infarction appeared to include significantly more female patients (20 (30.3%) versus 15 (15.3%) in the group of patients with unstable angina pectoris, p=0.02). However, by such parameters as the average age, left ventricular ejection fraction, and the frequency of diabetes mellitus the compared groups did not differ. The group with myocardial infarction was characterised by a severe clinico-angiographic status: more frequently encountered was stage II obesity (3%, n=3 in the first group and 10.6% n=7 in the second group, p=0.04). On the whole, the majority of patients were at intermediate and high risk (44.7% in the group with unstable angina pectoris versus 81.8% in the group of myocardial infarction, p<0.05). Group Two patients significantly more often presented with three-vessel lesions of the coronary bed (40 (40.8%) and 39 (59%), p=0.02). The level of low-density lipoproteins appeared to be significantly higher in patients with myocardial infarction (3.3±1 mmol/l and 2.9±0.9, p=0.04). In the same group more often encountered were peripheral artery lesions (28 (21%) and 12 (11.3%), p=0.04). In its turn, in the group of unstable angina pectoris, there were significantly more patients having received dual antithrombotic therapy prior to surgery (44 (44.9%) and 17 (25%), p=0.01). Approximately half of the patients in the first group (53%, n=52) had a history of myocardial infarction (p=0.001). The obtained findings suggested that amongst the patients with non-ST-elevation acute coronary syndrome resulting in myocardial infarction prevailing were those of female gender, with obesity, as a consequence, hyperholesterolaemia and triple-vessel disease. At the same time, postinfarction cardiosclerosis, renal dysfunction, and haemodynamically significant lesions of lower-extremity arteries were encountered in the group of unstable angina pectoris.

P34 The effect of sex on the efficacy and safety of dabigatran dual therapy in atrial fibrillation after PCI: a subgroup analysis from the RE-DUAL PCI trial

Abstract Funding Acknowledgements Boehringer Ingelheim International GmbH On Behalf The Re-DUAL PCI Investigators Background The RE-DUAL PCI study (NCT02164864) compared dabigatran dual antithrombotic therapy (D-DAT) with warfarin triple antithrombotic therapy (W-TAT) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). As previously reported D-DAT reduced bleeding compared with W-TAT and was non-inferior with regard to thromboembolic events. Aim The aim of this subgroup analysis of RE-DUAL was to assess the relationship between sex and treatment effects of D-DAT and W-TAT on bleeding and thromboembolic outcomes. Methods Patients were randomized to receive W-TAT (warfarin, clopidogrel or ticagrelor, and aspirin) or D-DAT (dabigatran 110 or 150 mg twice daily with clopidogrel or ticagrelor; D110- or D150-DAT). Younger patients (aged &amp;lt; 80 yrs. [&amp;lt; 70 yrs. in Japan]) and US patients irrespective of age received D110-DAT, D150-DAT or W-TAT; older patients (aged ≥ 80 yrs. in non-US countries [≥ 70 yrs. in Japan]) received only D110-DAT or W-TAT. Bleeding and thromboembolic outcomes were assessed according to treatment group and by sex (female vs. male). Results A total of 2725 patients were randomized; 2070 patients were male (76.0%) and 655 (24.0%) were female. Overall females were older at time of PCI than males (73.2 ± 7.9 vs. 70.0 ± 8.8 years). The mean CHA2DS2-VASc and modified HAS-BLED scores were higher in women at 4.5 and 2.8, respectively, than in men at 3.3 and 2.7, respectively. For the primary endpoint of major bleeding events or clinically relevant non-major bleeding events, treatment effects of D110-DAT vs. W-TAT were consistent for female and male patients (females: HR 0.69, 95% CI 0.47-1.01, males HR 0.46, 95%CI 0.37-0.59, interaction p-value 0.084). Similarly, consistent treatment effects were seen for the primary endpoint with D150-DAT vs W-TAT in female and male patients (females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value 0.83). No interaction between sex and treatment was observed for D110- or D150-DAT vs W-TAT with regard to the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization (interaction p values 0.73 and 0.72, respectively) (figure). Conclusion The treatment effect of dabigatran 110 mg and 150 mg dual therapy vs warfarin triple therapy was consistent across sex groups. This suggests that female and male patients with AF undergoing PCI should be treated equally in terms of the dosage of dabigatran selected for dual therapy strategies. Abstract P34 Figure. Re-DUAL sex subgroup analysis

Ultrasound-guided axillary vein puncture for cardiac devices implantation in patients under antithrombotic therapy

BackgroundUltrasound-guided axillary venous puncture (UGAVP) for cardiac devices implantation has been developed because of its rapidity, safety and potential long-term lead protection. Early work excluded defibrillators (ICD), cardiac resynchronization therapy (CRT) and upgrade procedures. Compared to the cephalic approach, in previous studies, there was a greater use of pressure dressings with this technique, suggesting a higher risk of bleeding. AimsTo assess UGAVP in patients under antithrombotic therapy (ATT) undergoing cardiac devices implantation including CRT/ICD. MethodsProspectively, consecutive patients eligible for a pacemaker or ICD implantation were included. All procedures were performed by a single operator, experienced with UGAVP for femoral access, and fluoroscopy-guided axillary vein access. Guidewires insertion time (from lidocaïne administration), and complications were systematically studied. ResultsFrom 457 cardiac device implantations, 200 patients (77.8 ± 10 y, male 58%) 360 leads were implanted by UGAVP including 36 ICD, 54 CRT and 14 upgrade procedures. A majority (90%) was under ATT: Vitamin K Antagonist or Heparin (n = 58, 29%), direct oral anticoagulant (n = 46, 23%), dual antithrombotic therapy (n = 18, 9%) and single antiplatelet drug (n = 82, 41%). UGAVP was successful in 95.78%. Mean insertion time for 1.8 guidewires per patient was 4.68 ± 3.6 min. No complication (no hematoma) was observed during the follow-up (mean of 45 ± 10 months). Guidewires insertion time reached its plateau after 15 patients. ConclusionUGAVP is fast, feasible and safe for patients under ATT undergoing device implantation including CRT/ICD and upgrade procedures, with a short learning curve.

Dabigatran Dual Therapy Versus Warfarin Triple Therapy Post–PCI in Patients With Atrial Fibrillation and Diabetes

ObjectivesThe aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial. BackgroundIt is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention. MethodsIn RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization. ResultsAmong patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints. ConclusionsIn this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Switching of Oral Anticoagulation Therapy After PCI in Patients With Atrial Fibrillation: The RE-DUAL PCI Trial Subanalysis

ObjectivesThe aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y12 inhibitor) versus warfarin triple therapy (warfarin plus a P2Y12 inhibitor plus aspirin) in patients with atrial fibrillation who underwent percutaneous coronary intervention (PCI). BackgroundIn the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI. MethodsA total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive. ResultsRisk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups. ConclusionsBleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.

TRIPLE VERSUS DUAL ANTITHROMBOTIC THERAPY FOR PATIENTS WHO REQUIRE ORAL ANTICOAGULATION AND UNDERGO PERCUTANEOUS CORONARY INTERVENTION: AN UPDATED META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Patients who require chronic oral anticoagulation (OAC) due to conditions such as atrial fibrillation (AF) require additional antiplatelet therapy when they undergo percutaneous coronary intervention (PCI). Current treatment options include triple antithrombotic therapy (dual antiplatelet agent [DAPT] + OAC) or dual antithrombotic therapy (single antiplatelet agent [SAPT] + OAC). There is a need to identify an optimal antithrombotic regimen in this patient population since the choice of therapy can impact both bleeding and ischemic events. We performed an updated meta-analysis of randomized controlled trials (RCTs) comparing triple antithrombotic therapy (OAC+DAPT) vs. dual antithrombotic therapy (OAC + SAPT) after PCI, including the recently completed and largest trial to date (AUGUSTUS). Searching MEDLINE and Pubmed, we performed a meta-analysis of RCTs which enrolled patients undergoing elective or urgent (due to acute coronary syndrome) PCI who were randomized to receive triple or dual antithrombotic therapy. The triple antithrombotic therapy group was treated using a strategy of OAC with either warfarin or non-vitamin K oral anticoagulant (NOAC), and DAPT (acetylsalicylic acid + P2Y12 inhibitor). The dual antithrombotic therapy group was treated with OAC, either warfarin or NOAC, in combination with SAPT consisting of either acetylsalicylic acid or a P2Y12 inhibitor. Using random effects models, we determined pooled risk ratios (RR) of clinically significant bleeding, stent thrombosis, myocardial infarction (MI), and stroke with 95% confidence intervals (CI) comparing patients randomized to triple vs. dual antithrombotic therapy. Four RCTs examining 10,026 total patients were pooled. There was a 40% reduction in clinically relevant bleeding (RR 0.60 [95% CI; 0.49-0.73]) observed among patients treated with dual vs. triple antithrombotic therapy. Patients treated with dual antithrombotic therapy demonstrated a 17% increased risk of MI (RR 1.17 [95% CI; 0.94-1.46]) and a 20% increased risk of stent thrombosis (RR 1.20 [95% CI; 0.66-2.16]) which were statistically non-significant. The risk of stroke was similar between the two therapy arms (RR 0.93 [95% CI; 0.63-1.36]) (Figure). Among patients undergoing PCI treated chronically with OACs, dual antithrombotic therapy (OAC+SAPT) significantly reduced bleeding and had similar stroke risk compared to triple antithrombotic therapy (OAC+DAPT). While patients treated with dual antithrombotic therapy had a numeric increase in their risk of MI and stent thrombosis, this did not reach statistical significance. Thus, the lower bleeding risk observed with dual antithrombotic therapy may be associated with a trade-off for a higher risk of myocardial ischemic events.

DUAL ANTITHROMBOTIC THERAPY IS SAFE AND EFFECTIVE IN PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING PCI: UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

Optimal antithrombotic therapy regimen in patients with atrial fibrillation (AF), presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI) is unclear. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of dual versus triple antithrombotic therapy. MEDLINE, EMBASE, and Web of Science were systematically searched. All randomized trials of dual versus triple antithrombotic therapy were included. The primary safety and efficacy outcomes were Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding and myocardial infarction (MI), respectively. Secondary outcomes included stent thrombosis, stroke, trial-defined major adverse cardiac events (MACE) and cardiac death. Bayesian network meta-analyses and subgroup analyses were pre-specified. Hazard ratios (HR, 95%CI) were calculated using random-effects model. Five trials involving 9,961 patients were included (73% male; mean age 71 years). Compared to triple antithrombotic therapy (TAT), dual antithrombotic therapy (DAT) resulted in a 48% reduction in TIMI major or minor bleeding (4.0% vs. 7.7%, HR 0.52, 95%CI 0.42-0.65, I2= 22%, p < 0.001). There were no significant differences in ischemic outcomes of MI (3.4 % vs. 2.9%, HR 1.14, 0.90-1.45, I2= 0%, p=0.27), stent thrombosis (0.98% vs. 0.70%, HR 1.26, 0.69-2.29), stroke (1.1% vs. 1.1%, HR 0.93, 0.62-1.40), trial-defined MACE (9.1% vs. 8.2%, HR 0.94, 0.74-1.19), or cardiac death (2.6% vs. 2.4%, HR 1.00, 0.74-1.34). Network meta-analysis pairwise comparisons for TIMI major or minor bleeding showed significantly lower bleeding with DAT-NOAC compared to TAT-VKA (OR 0.43, 95% CrI 0.21-0.91). Subgroup analyses showed that trial-specified bleeding was significantly lower for dual antithrombotic therapy compared to triple antithrombotic therapy regardless of age (interaction p-value=0.21), sex (p=0.32), ACS or elective indication for PCI (p=0.75), and presence of diabetes (p=0.38). Compared to triple therapy, dual antithrombotic therapy resulted in reduced bleeding without a significant increase in ischemic events. Current evidence supports the use of dual antithrombotic therapy over triple therapy for patients with AF following PCI.

P4786Dual antithrombotic therapy is similarly effective to triple therapy in preventing thrombotic events in patients with atrial fibrillation and acute coronary syndrome

Abstract Background Antithrombotic therapy is effective in preventing ischemic and thromboembolic events, however it simultaneously increases the risk of bleeding. The efforts thus focus on balancing the intensity of combined antiplatelet and anticoagulant therapy. Purpose The study aimed to compare efficacy and safety of single (aspirin/clopidogrel) or dual (aspirin plus clopidogrel) antiplatelet therapy in combination with an oral anticoagulant in non-selected patient population with atrial fibrillation (AFib) and an acute coronary syndrome (ACS). Methods The analysis used data from National Registry of Reimbursed Health Services (NRRHS), which contains data of the entirety of health care paid from the public health insurance (almost 100% of healthcare in the Czech Republic) combined with the database of death records. Occurrence of an ACS, stroke, and bleeding requiring hospitalization within one year was compared in patients discharged on dual and triple antithrombotic therapy. Dual antithrombotic therapy consists of aspirin/clopidogrel plus an oral anticoagulant. Triple antithrombotic therapy was defined as combination of aspirin, clopidogrel and an oral anticoagulant. Results Over a four-year period (2012–2016) 104 000 patients with an ACS were hospitalized in the Czech Republic. AFib (any types) was reported in 12.4% (N=12 891) of them (21.2% in patients 75+ years old). +AFib (vs. −AFib) patients were a higher risk population with respect to the comorbidity (diabetes, hypertension, renal disease, stroke, heart failure) (p&lt;0.05 for all comorbidities). Oral anticoagulant therapy was indicated in 25.3% of them. PCI was performed in 57.7% (−AFib) and 43.4% (+AFib) patients, respectively. Hospital mortality was significantly higher in +AFib patients (8.6% and 5.6%, OR (95% CI): 1.585 (1.481; 1.696), p&lt;0.001). We identified 1017 patients discharged on dual and 967 patients on triple antithrombotic therapy. Risk of recurrent ACS within one year with dual therapy was comparable to that with triple therapy (OR (95% CI): 1.219 (0.766; 1.940), p=0.403). The same was also observed for the risk of stroke (1.273 (0.648; 2.501), p=0.483). After six months, persistence on dual antithrombotic therapy (33.4% patients) was higher than on triple therapy (10.3%, p&lt;0.001). Within the first three months, de-escalation from triple antithrombotic therapy to dual antithrombotic therapy (in 212 patients) was accompanied by a significant increase of bleeding requiring hospitalization (0% on dual vs. 3.3% on triple therapy, p=0.048). Conclusion Protective effect of dual antithrombotic therapy on the occurence of recurrent major adverse cardiovascular event is comparable to that of the triple antithrombotic therapy in non-selected patients with an acute coronary syndrome and atrial fibrillation. Moreover, long-term persistence on triple therapy is significantly lower due to bleeding risk.

DUAL ANTITHROMBOTIC THERAPY WITH DIRECT-ACTING ORAL ANTICOAGULANTS AFTER ACUTE CORONARY SYNDROME OR PCI IN ATRIAL FIBRILLATION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

The choice of antithrombotic therapy for patients with atrial fibrillation (AF) who have an acute coronary syndrome (ACS) or have undergone PCI is challenging. A dual antithrombotic therapy with Direct-acting oral anticoagulants (DOACs) plus an antiplatelet agent has emerged as an alternative regimen to the standard triple antithrombotic therapy with warfarin plus two antiplatelet agents after PCI or ACS for patients with AF. The aim of the study was to assess the outcomes between dual antithrombotic therapy with DOACs plus an antiplatelet agent in comparison to warfarin plus two antiplatelet agents after PCI or ACS for patients with AF. Systematic searches of multiple major databases were performed from inception until April 2019. We included only randomized controlled trials (RCTs) of adults that compared safety and efficacy of dual antithrombotic therapy with DOACs plus an antiplatelet agent to triple antithrombotic therapy with warfarin plus two antiplatelet agents after PCI or ACS for patients with AF. The primary (safety) outcomes were: 1) major bleeding and 2) major bleeding or clinically relevant non-major bleeding. The secondary (efficacy) outcomes were: 1) death and 2) composite of death or ischemic events (stroke or myocardial infarction). Odd ratios were pooled using a random-effects model, and individual studies were weighted using inverse variance. We identified 3 RCTs that included 5662 patients. Dual antithrombotic therapy with DOACs was used in 2830 patients. Baseline characteristics were similar in both groups. In comparison to triple antithrombotic therapy with warfarin, Dual antithrombotic therapy with DOACs was associated with a significant reduction in major bleeding (odds ratio [OR] 0.48 [95% confidence interval [CI] 0.37 to 0.61], p < 0.001) as well as major bleeding or clinically relevant non-major bleeding (OR 0.47 [95% CI 0.35 to 0.62], p < 0.001). There was a trend of higher rate of the composite of death or ischemic events (stroke or myocardial infarction) with Dual antithrombotic therapy with DOACs (OR 1.21 [95% CI 0.99 to 1.49], p=0.06). There was no significant difference between both groups in the rate of death (OR 1.18 [95% CI 0.89 to 1.57], p=0.25). In patients with AF and recent ACS or PCI, the use of dual antithrombotic therapy with DOACs was associated with less major bleeding, and major bleeding or clinically relevant non-major bleeding. The use of Dual therapy has shown non-significantly higher composite of death or ischemic events (stroke or myocardial infarction) but no difference in mortality.

Dual Pathway Inhibition in Atherosclerosis - Which Patients Benefit?

Dual antithrombotic therapy (DAT) with low-dose rivaroxaban in combination with acetylsalicylic acid (ASA) is available to patients with stable atherosclerotic disease as a new therapeutic option.The results of the COMPASS trial demonstrate a significant relative risk reduction of cardiovascular outcomes by 24 % with low-dose DAT in patients with stable peripheral arterial disease or coronary heart disease.Despite a guideline adherent secondary prevention therapy, the cardiovascular event rate with ASA alone during the mean study period of almost two years was 5.4 %. The absolute reduction of the event rate by the low-dose DAT is low at 1.3 %. Consequently, it is important to identify groups of patients at high risk for cardiovascular events. These patients are particularly qualified to receive a DAT regimen and can be characterized using high-risk features.The individual ischemic risk profile may be further defined by the presence of polyvascular atherosclerosis, concomitant diseases, and ischemic events in the past. The quo ad vitam reduced prognosis of patients with polyvascular atherosclerosis advocates a polyvascular screening, even in supposedly stable patients with coronary heart disease and peripheral arterial disease.An intensification of antithrombotic therapy is naturally associated with an increased risk of bleeding. Therefore, the risk-reduction of ischemic events should be weighed individually against the risk of bleeding.A low-dose DAT is particularly suitable for patients with a high ischemic risk and a low risk of bleeding.

TCT-403 Dual Antithrombotic Therapy Is Safe and Effective in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Updated Systematic Review and Meta-Analysis

Optimal antithrombotic therapy regimen in patients with atrial fibrillation, presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention is unclear. The authors performed a systematic review and meta-analysis to evaluate the safety and efficacy of dual versus triple

Dual antithrombotic therapy for atrial fibrillation and PCI

Dual antithrombotic therapy for atrial fibrillation and PCI

More Support for Dual Antithrombotic Therapy After PCI in Patients with Atrial Fibrillation

In the wake of several randomized trials evaluating short-term anticoagulation strategies for patients with atrial fibrillation (AF) who undergo