Concomitant Dual Antiplatelet Therapy Research Articles

DOACs vs Vitamin K Antagonists During Cardiac Rhythm Device Surgery: A Multicenter Propensity-Matched Study

BackgroundThere is a paucity of data comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) at the time of cardiac implantable electronic device (CIED) surgery. Furthermore, the best management of DOACs (interruption vs continuation) is yet to be determined. ObjectivesThis study aimed to compare the incidence of device-related bleeds and thrombotic events based on anticoagulant type (DOAC vs VKA) and regimen (interrupted vs uninterrupted). MethodsThis was an observational multicenter study. We included patients on chronic oral anticoagulation undergoing CIED surgery. Patients were matched using propensity scoring. ResultsWe included 1,975 patients (age 73.8 ± 12.4 years). Among 1,326 patients on DOAC, this was interrupted presurgery in 78.2% (n = 1,039) and continued in 21.8% (n = 287). There were 649 patients on continued VKA. The matched population included 861 patients. The rate of any major bleeding was higher with continued DOAC (5.2%) compared to interrupted DOAC (1.7%) and continued VKA (2.1%) (P = 0.03). The rate of perioperative thromboembolism was 1.4% with interrupted DOAC, whereas no thromboembolic events occurred with DOAC or VKA continuation (P = 0.04). The use of dual antiplatelet therapy, DOAC continuation, and male sex were independent predictors of major bleeding on a multivariable analysis. ConclusionsIn this large real-world cohort, a continued DOAC strategy was associated with a higher bleeding risk compared to DOAC interruption or VKA continuation in patients undergoing CIED surgery. However, DOAC interruption was associated with increased thromboembolic risk. Concomitant dual antiplatelet therapy should be avoided whenever clinically possible. A bespoke approach is necessary, with a strategy of minimal DOAC interruption likely to represent the best compromise.

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI. In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose. In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0-12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p = 0.01). Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. ClinicalTrials.gov Identifier: NCT02611934.

Antiplatelet therapy in STEMI undergoing primary PCI: when, which one and how long.

Reperfusion therapy for patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) involves primary percutaneous coronary intervention (PPCI) and concomitant dual antiplatelet therapy (DAPT) with combination of a P2Y12 inhibitor and acetylsalicylic acid (ASA). Decision regarding DAPT can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. This review outlines the currently available antiplatelet treatments, and their place within the therapeutic timeline of a patient presenting with STEMI.

Safety of Percutaneous Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation after Acute Coronary Syndrome: A Single Center Experience

Aims: In patients with atrial fibrillation (AF) and indication to Dual Antiplatelet Therapy (DAPT) for Acute Coronary Syndrome (ACS), triple therapy is recommended. However, this issue is still largely debated. Percutaneous Left Atrial Appendage (LAA) occlusion may represent an alternative therapeutic approach in this subset of patients, as it could lead to a reduction in the incidence of bleeding. Nevertheless, due to lack of clinical evidence, this approach does not represent the gold standard treatment for these patients. The objective of this study is to evaluate the safety of percutaneous LAA occlusion in patients with Atrial Fibrillation and indication of concomitant DAPT for ACS. Methods and Results: Fifteen AF-patients with indications to anticoagulant and DAPT after ACS underwent LAA occlusion with Amplatzer Cardiac Plug (ACP) or Amulet ACP (St. Jude) from October 2014 to May 2016. Procedural success was achieved in 14/15 patients, while in 1 patient a clinically non-relevant pericardial effusion was registered before the trans-septal puncture, without implantation of the device. No peri-procedural death, major bleeding and dislocation or thrombi of the device were recorded. During a median follow-up of 182 days (interquartile range [IQR]: 169 to 183 days), one peri-procedural minor bleeding and two non cardiovascular death were described. Conclusions: LAA occlusion represents a relatively safe procedure for patients with atrial fibrillation and the need of DAPT due to ACS. Randomized trials should be designed to evaluate the efficacy and safety of this procedure in this clinical setting.

Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - aJapanese retrospective cohort study .

Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract. .

Safety of New Oral Anticoagulants with Dual Antiplatelet Therapy in Patients with Acute Coronary Syndromes

To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes. A literature search of MEDLINE (1946-January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references. Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review. Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding. The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.

Prasugrel During Primary Percutaneous Coronary Intervention: Evidence from Clinical Data

Primary percutaneous coronary intervention (PCI) encompassing stent implantation is a mainstay in the management of acute ST-elevation myocardial infarction (STEMI). Despite refinements in techniques and devices, peri- and post-procedural antithrombotic therapy remains pivotal to prevent early and late thrombotic events, without unduly increasing bleeding risk. Concomitant dual antiplatelet therapy with aspirin and clopidogrel has been considered until recently the standard of care in terms of oral antiplatelet agents. However, most recently a novel and more potent thienopyridine, prasugrel, has been tested in randomized trials including patients with STEMI, and subsequently approved for clinical practice in Europe and North America. Despite its potent antithrombotic effect, prasugrel also carries a statistically significant increase in the risk of bleeding, especially in the elderly, those with low body weight, and previous stroke or transient ischemic attack. Thus, the use of prasugrel, as well as that of clopidogrel or ticagrelor, should best be individualized to maximize clinical benefits and minimize hazards.

Coronary Stents and Chronic Anticoagulation

Case Presentation: A 76-year-old man was admitted with retrosternal chest pain. The ECG on admission showed inferolateral ST depression, and troponin levels were elevated, confirming the diagnosis of an acute coronary syndrome. The patient had a history of hypertension and aortic valve replacement with a metallic bileaflet valve 7 years before. He was being treated with warfarin and low-dose aspirin and had an international normalized ratio (INR) of 2.5. Coronary angiography revealed a long subocclusive lesion of the proximal right coronary artery. At that point, there was a question about the optimal treatment for this patient regarding the type of stent to be selected and the need for future combined antiplatelet and anticoagulation treatment. Oral anticoagulation was routinely used for coronary stent thrombosis prevention during the first era of stents.1 It has since been replaced by the combination of aspirin and a thienopyridine because studies have shown a definite advantage of the antiplatelet combination on coronary events2–4 and on reducing the risk of access-site bleeding complications. However, ≈5%5,6 of patients undergoing percutaneous coronary intervention (PCI) also present with an indication for oral anticoagulation therapy. In such cases, the type of stent selected; the use of oral anticoagulants, antiplatelets, or their combinations; the target INR; and the duration of treatment are essential considerations in relation to the risk of stent thrombosis/thromboembolic events and bleeding risk. With the introduction and widespread use of drug-eluting stents (DES) in recent years and given the necessity for longer duration of dual antiplatelet therapy, the issue of concurrent warfarin and antiplatelet therapy has become even more important. The existing guidelines do not offer a convincing solution to these issues. For acute coronary syndrome patients with an indication for anticoagulation, triple therapy (warfarin, aspirin, and clopidogrel) for the minimum time possible and a maintenance …

Risk of Major Bleeding with Concomitant Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients Receiving Long‐Term Warfarin Therapy

To characterize the safety of concomitant aspirin, clopidogrel, and warfarin therapy after percutaneous coronary intervention (PCI), and to identify patient characteristics that increase the risk of hemorrhage. Retrospective, matched cohort study. Academic medical center and affiliated outpatient offices. The active group consisted of 97 patients who underwent PCI from January 1, 2000-September 30, 2005, and received warfarin, aspirin, and clopidogrel; the control group consisted of 97 patients who were individually matched to patients in the active group by procedure type, procedure year, age, and sex. Control patients received aspirin and clopidogrel. Clinical data were collected from inpatient records, outpatient physician office records, and telephone surveys administered to patients or caregivers. The primary end point was major bleeding. The median duration of follow-up after index procedure was 182 days (range 0-191 days) in the active group and 182 days (range 0-213 days) in the control group. Fifty-seven (59%) of the 97 patients in the active group received warfarin for atrial fibrillation. There were 14 major bleeds in the active group (including 1 death) and 3 major bleeds in the control group during the study period. Mean international normalized ratio at the time of bleeding was 3.4. Hazard ratio for major bleeding was 5.0 in patients receiving warfarin therapy (95% confidence interval 1.4-17.8, p=0.012). Aspirin dose, age, sex, body mass index, history of hypertension, diabetes mellitus, intraprocedural glycoprotein IIb-IIIa or anticoagulant type, and postprocedural anticoagulant use did not have a significant effect on the risk of major bleeding. Warfarin was an independent predictor of major bleeding after PCI in patients receiving dual antiplatelet therapy. Prospective data to further characterize the safety of concomitant warfarin and dual antiplatelet therapy after PCI are needed.