Aspirin and Clopidogrel Inhibit Aneurysm Healing after HydroCoil Implantation in External Carotid Artery Aneurysm Model.

PURPOSE: To understand whether the use of antiplatelet agents leads to less intra-aneurismal tissue formation following coil implantation in a rat end-pouch external carotid artery (ECA) aneurysm model. METHODS: End-pouch ECA aneurysms were created in adult rats and were then embedded with either platinum or HydroCoils. Rats were treated either with aspirin, clopidogrel, aspirin + clopidogrel, or saline for 2 weeks after coil implantation. At 2 weeks after coil implantation, rats were sacrificed and the aneurysm pouch was removed for histological and immunohistochemical analysis. A blinded single observer calculated the percentage of the organized area and the residual length of elastic lamina within the aneurysm. Student's t-test was used to compare data from image analysis between the different groups. RESULTS: Within the platinum group, the organized tissue area was not affected by antiplatelet administration (aspirin versus saline, P = .83; clopidogrel versus saline, P = .46; aspirin + clopidogrel versus saline, P = .54). For the HydroCoil group, the organized tissue area was significantly reduced (aspirin versus saline, P = .02; clopidogrel versus saline, P = .04; aspirin + clopidogrel versus saline, P = .02) in rats treated with antiplatelet agents; however, no difference (aspirin versus clopidogrel, P = .8; aspirin versus aspirin + clopidogrel, P = .3; clopidogrel versus aspirin + clopidogrel, P = .5) was found among type or combination of antiplatelets administered. HydroCoil-treated aneurysms had a similar number of macrophages compared to the platinum group (P = .3819); however, the HydroCoil group had significant suppression of macrophages in the groups treated with combined antiplatelets (P = .02). CONCLUSION: Following HydroCoil implantation, the area of organized tissue is diminished significantly in a rat end-pouch ECA aneurysm model treated with antiplatelets.

An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

The role of triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel forms the backbone of secondary prevention in patients with acute coronary syndromes (ACS) or who undergo percutaneous coronary intervention (PCI), but in patients with atrial fibrillation (AF), oral anticoagulation (OAC) is superior to antiplatelet therapy for the prevention of stroke and systemic embolism. Patients with AF who undergo PCI or have an ACS event therefore have an indication for both OAC and DAPT, so-called triple antithrombotic therapy. However, observational analyses have shown that the annual rate of major bleeding on triple therapy exceeds 10%. For this reason, five major randomized clinical trials have compared double antithrombotic therapy with OAC and a P2Y12 inhibitor versus triple therapy in patients with AF who underwent PCI or had an ACS event. Each of the trials showed that double antithrombotic therapy reduced the rate of major and clinically relevant non-major bleeding compared with triple therapy and was non-inferior for prevention of ischemic events, including cardiovascular death, myocardial infarction, or stroke. In the one trial that directly compared warfarin with a non-vitamin K antagonist oral anticoagulant (NOAC), apixaban reduced the rate of major or clinically relevant non-major bleeding compared with warfarin and was non-inferior with respect to prevention of ischemic events. As a result of these trials, consensus guidelines recommend that patients with AF who undergo PCI or have an ACS event should be treated with triple antithrombotic therapy (OAC + P2Y12 inhibitor + aspirin) for 7 days or less, followed by double antithrombotic therapy (OAC + P2Y12 inhibitor) for 6 to 12 months.

Non-Persistence With Antiplatelet Medications Among Older Patients With Peripheral Arterial Disease.

Introduction: Antiplatelet therapy needs to be administered life-long in patients with peripheral arterial disease (PAD). Our study was aimed at 1) the analysis of non-persistence with antiplatelet medication in older PAD patients and 2) identification of patient- and medication-related characteristics associated with non-persistence. Methods: The study data was retrieved from the database of the General Health Insurance Company. The study cohort of 9,178 patients aged ≥ 65 years and treated with antiplatelet medications was selected from 21,433 patients in whom PAD was newly diagnosed between 01/2012 and 12/2012. Patients with a 6 months treatment gap without antiplatelet medication prescription were classified as non-persistent. Characteristics associated with non-persistence were identified using the Cox regression. Results: At the end of the 5 years follow-up, 3,032 (33.0%) patients were non-persistent. Age, history of ischemic stroke or myocardial infarction, clopidogrel or combination of aspirin with clopidogrel used at the index date, higher co-payment, general practitioner as index prescriber and higher overall number of medications were associated with persistence, whereas female sex, atrial fibrillation, anxiety disorders, bronchial asthma/chronic obstructive pulmonary disease, being a new antiplatelet medication user (therapy initiated in association with PAD diagnosis), and use of anticoagulants or antiarrhythmic agents were associated with non-persistence. Conclusion: In patients with an increased probability of non-persistence, an increased attention should be paid to improvement of persistence.

Treatment of the Dental Patient with Bleeding Dyscrasias: Etiologies and Management Options for Surgical Success in Practice.

The oral health care provider sees a significant number of patients in his or her practice who suffer from systemic diseases affecting the ability to clot. These medical issues can be acquired or inherited bleeding dyscrasias requiring pharmacologic therapy during the perioperative period. Patients with inherited or acquired bleeding disorders require careful attention with respect to the assessment of bleeding risk. This article develops algorithms to manage acquired and inherited bleeding dyscrasias. These approaches include a discussion of the epidemiology of bleeding disorders in surgical patients, mechanism of hemostasis, and strategies for patient management based on the etiology of bleeding disorder.

Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction.

Delays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30-120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI.

Effect of P2Y12 inhibitors on inflammation and immunity.

Platelet P2Y12 inhibitors form a major part of the treatment strategy for patients with acute coronary syndromes (ACS) due to the importance of the platelet P2Y12 receptor in mediating the pathophysiology of arterial thrombosis. It has been increasingly recognised that platelets also have a critical role in inflammation and immune responses. P2Y12 inhibitors reduce platelet release of pro-inflammatory α-granule contents and the formation of pro-inflammatory platelet-leukocyte aggregates. These are important mediators of inflammation in a variety of different contexts. Clinical evidence shows that P2Y12 inhibition by clopidogrel is associated with a reduction in platelet-related mediators of inflammation, such as soluble P-selectin and CD40L, following atherothrombosis. Clopidogrel in addition to aspirin, compared to aspirin alone, also reduces markers of systemic inflammation such as tumour necrosis factor (TNF) α and C-reactive protein (CRP) following ACS. The more potent thienopyridine P2Y12 inhibitor, prasugrel, has been shown to decrease platelet P-selectin expression and platelet-leukocyte aggregate formation compared to clopidogrel. The PLATO study suggested that the novel P2Y12 inhibitor ticagrelor might improve clinical outcomes from pulmonary infections and sepsis compared to clopidogrel in patients with ACS. Ticagrelor is a more potent P2Y12 inhibitor than clopidogrel and also inhibits cellular adenosine uptake via equilibrative nucleoside transporter (ENT) 1, whereas clopidogrel does not. Further examination of the involvement of these mechanisms in inflammation and immunity is therefore warranted.

Antiplatelet agents and proton pump inhibitors - personalizing treatment.

INTRODUCTION: Antiplatelet therapy remains one of the cornerstones in the management of non-cardioembolic ischemic stroke. However, a significant percentage of patients have concomitant gastroesophageal reflux or peptic ulcer disease that requires acid-reducing medications, the most powerful and effective being the proton pump inhibitors (PPIs). Antiplatelet efficacy, at least in vivo, and particularly for clopidogrel, has been shown to be reduced with concomitant proton pump inhibitor use. Whether this is clinically relevant is not clear from the limited studies available. METHODS: We conducted an extensive review of studies available on Medline related to pharmacodynamic interactions between the antiplatelet medications and proton pump inhibitors as well as clinical studies that addressed this potential interaction. RESULTS: Based on the present pharmacodynamic and clinical studies we did not find a significant interaction that would reduce the efficacy of antiplatelet agents with concomitant user of proton pump inhibitors. CONCLUSIONS: Patients on antiplatelet agents after a transient ischemic attack or ischemic stroke can safely use aspirin, and extended release dipyridamole/aspirin with proton pump inhibitors. Patients on clopidogrel may use other acid-reducing drugs besides proton pump inhibitors. In rare cases where proton pump inhibitors and clopidogrel have to be used concurrently, careful close monitoring for recurrent vascular events is required.