Administration Of Dual Antiplatelet Therapy Research Articles

Inadvertent administration of dual antiplatelet therapy to a patient with an indwelling epidural catheter

SummaryWe describe the case of a middle‐aged patient who suffered a non‐ST elevation myocardial infarction (NSTEMI) on day 1 postoperatively following an elective abdominal aortic aneurysm (AAA) repair. The NSTEMI was managed with dual antiplatelet therapy; unfortunately this was initiated without due consideration to the fact he had an epidural in situ. Once this clinical conflict was identified, careful decisions were taken regarding concurrent management of his NSTEMI and epidural, particularly regarding timing of catheter removal. The patient suffered no neurological sequelae.The case raises two clear learning points. Firstly, it highlights the logistical and ethical difficulties of managing serious medical conditions when treatments expose patients to significant harm. Secondly, it emphasises the contribution of human factors to medical errors in anaesthesia and intensive care. As a result of this case, we developed bedside epidural alert notices in our institution to reduce the risk of similar incidents occurring in the future.

How long should dual antiplatelet therapy be continued following implantation of drug eluting stents?

Drug eluting stents (DES) are now established in the treatment of coronary artery disease (1) and their development promised to improve upon limitations associated with original bare metal stents in particular that of late restenosis. Whilst restenosis rates have improved, DES have been claimed to be associated with a higher risk of late stent thrombosis (2). The administration of dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12-receptor inhibitor following implantation of DES significantly reduces the likelihood of coronary stent thrombosis (ST) due to inflammation of the stented segmented during healing (3) and for this reason is deemed mandatory in all patients following DES implantation. DAPT is also associated with additional benefits (unrelated to the stented coronary artery segment) and has been associated with a reduction in ischemic events and an improvement of clinical outcomes (4). However, these benefits are limited by a significant increase in bleeding and therefore current guidelines recommend that DAPT should be administered for 6-12 months following DES (1) with recent studies investigating the feasibility of further reducing the length of DAPT in a bid to further improve safety without exposing patients to unnecessary risks (5-7). However, the current reality is that the most effective duration of DAPT to prevent both stent thrombosis and further ischemic events (e.g., myocardial infarction) remains to be determined and the effects of prolonged DAPT beyond the currently recommended 12 months are poorly characterised.

USE OF DUAL ANTIPLATELET VERSUS SINGLE ANTIPLATELET THERAPY FOR PREVENTION OF RECURRENT ISCHEMIC STROKE: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Antiplatelet agents are used for secondary prevention in patients with ischemic stroke or transient ischemic attack. Emerging studies suggest that early administration of dual antiplatelet therapy (DAPT) may be better than single antiplatelet therapy for the prevention of recurrent ischemic stroke,

Dual Antiplatelet Therapy for Coronary Artery Disease

Platelets initiate the formation of a thrombus at the site of an arterial injury, and the clotting cascade is activated as the thrombus matures. After coronary stent placement, dual antiplatelet therapy (DAPT) with aspirin and ticlopidine dramatically reduces the risk of stent thrombosis, compared with anticoagulation therapy, and has become the standard of care for prevention of stent thrombosis. Clopidogrel is a second-generation thienopyridine that eliminates the serious side effects of ticlopidine, and new P2Y12 receptor blockers have emerged to overcome the limitations of clopidogrel. Current guidelines recommend DAPT with aspirin and clopidogrel for 1 month after implantation of bare-metal stents, and for 6-12 months after implantation of drug-eluting stents (DES). In patients with acute coronary syndrome (ACS), DAPT administration for 12 months was shown to be superior to aspirin alone for the prevention of recurrent events. Treatment with aspirin and new P2Y12 receptor blockers has further reduced the rate of cardiovascular death, myocardial infarction or stroke after ACS compared with aspirin and clopidogrel. Nonetheless, long-term DAPT increases the risk of major bleeding, requiring a delicate balance between anti-ischemic benefit and bleeding risk. In summary, DAPT should be maintained for at least 6-12 months after implantation of DES, and for at least 12 months after ACS, unless contraindicated.

P-007 Incidence and Management of Intimal Hyperplasia at 6 months after Flow Diversion for Intracranial Aneurysms

Introduction/purposeA new option in the treatment of large and complex intracranial aneurysms centerd along the cavernous/intradural segment of the ICA, proximal to the PCom artery, includes the utilization of flow-diverter...

Upstream administration of oral antiplatelet agents in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Current guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) recommend the administration of dual antiplatelet therapy with aspirin and an ADP receptor blocker "as early as possible" before angiography (upstream), though this suggestion is not based on the results of randomized clinical trials designed to investigate pre-hospital rather than in-hospital drug administration. The present review analyzed randomized clinical trials, registries and observational studies that assessed clopidogrel, prasugrel and ticagrelor administration in STEMI patients undergoing primary PCI to evaluate if their upstream use may be justified in clinical practice. A significant difference favoring early clopidogrel administration has been demonstrated in observational studies. No evidence is available for prasugrel and ticagrelor; however, the initial delay of their antiplatelet effect in STEMI patients could support an upstream strategy to obtain complete platelet inhibition in the first hours after PCI and prevent major adverse events (e.g., stent thrombosis) despite an increased risk of major bleeding, particularly in case of urgent bypass surgery. Data from specifically designed randomized clinical trials are warranted to establish whether early administration of prasugrel and ticagrelor may favor reperfusion and improve clinical outcome with an acceptable risk-benefit ratio.

Waffle Y technique: pCONus for tandem bifurcation aneurysms of the middle cerebral artery

Broad based bifurcation aneurysms are challenging. Various endovascular techniques aim at stabilizing the coil package in the aneurysm. Among these, the waffle cone technique provides a viable alternative to Y...

Early Dual Versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack

Background— Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA. Methods and Results— We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60–0.80; P <0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63–0.81; P <0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70–2.59, P =0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results. Conclusions— For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world.

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A comparison of the metabolism of clopidogrel and prasugrel

Importance of the field: The administration of dual antiplatelet therapy with aspirin and a thienopyridine for the prevention of thrombosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention is proven to reduce mortality. The original thienopyridine, ticlopidine, has largely been displaced by clopidogrel, which has a superior adverse effect profile. Prasugrel is a new thienopyridine that has been purported to have a faster onset of activity, a lower rate of nonresponders and a greater potency than clopidogrel.Areas covered in this review: This review compares the metabolism of clopidogrel and prasugrel by carboxylesterases and the CYP system with emphasis on the formation of their respective active metabolites.What the reader will gain: The reader will gain an understanding of the pharmacokinetics of prasugrel and clopidogrel and how the differences in their respective metabolic pathways explain the difference in their therapeutic activity.Take home message: The superior therapeutic profile of prasugrel is explained by the different roles of carboxylesterases in their metabolic pathways. Though prasugrel is superior to clopidogrel as a prodrug of the active P2Y12 inhibitor, caution is advised because limited information is available on genetic polymorphisms or drug interactions affecting carboxylesterase metabolism.

AS-276: Optimal Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation: A Randomized, Multicenter DES-LATE Trial

Long-term safety of drug-eluting stents (DES) was a serious concern because of increased risk of late-occurring stent thrombosis, death, or myocardial infarction (MI). These serious outcomes can be reduced by administering dual antiplatelet therapy (DAPT), but optimal duration of DAPT administration following DES implantation has not been validated.

Noncardiac Surgery for Patients with Coronary Artery Stents

Physicians are increasingly being confronted with questions regarding the appropriate management of patients with recently implanted coronary stents who are in need of noncardiac surgery. Specifically, what is the optimal timing of elective procedures and how should antiplatelet therapy be managed in these patients, especially in those in need of emergent procedures? Continued antiplatelet therapy through the perioperative period might increase the risk of surgical bleeding while interruption of antiplatelet therapy predisposes to stent thrombosis, particularly in the setting of systemic hypercoagulation that frequently occurs after some surgeries.1 In this issue of Anesthesiology, two papers from the Mayo Clinic in Rochester, Minnesota provide further insight into these perplexing issues.2,3

Intracranial hemorrhage associated with stent-assisted coil embolization of cerebral aneurysms: a cautionary report

The introduction of the Neuroform microstent has facilitated the embolization of complex cerebral aneurysms, which were previously not amenable to endovascular therapy. Typically, the use of this stent necessitates the administration of dual antiplatelet therapy to minimize thromboembolic complications. Such therapy may increase the risk of hemorrhage in patients who require concurrent external ventricular drainage and/or subsequent permanent cerebrospinal fluid diversion. The authors' neurosurgical database was queried for all patients who underwent stent-assisted coil embolization for cerebral aneurysms and who required an external ventricular drain (EVD) or ventriculoperitoneal (VP) shunt placement for management of hydrocephalus. Thirty-seven patients underwent stent-assisted coil embolization for intracranial aneurysms at the authors' institution over a recent 2-year period. Seven of these patients required placement of an EVD and/or a VP shunt. Three of the 7 patients suffered an immediate intraventricular hemorrhage (IVH) associated with placement or manipulation of an EVD; 1 experienced a delayed intraparenchymal hemorrhage and an IVH; 1 suffered an aneurysmal rehemorrhage; and the last patient had a subdural hematoma (SDH) that resulted from placement of a VP shunt. This patient required drainage of the SDH and exchange of the valve. The necessity of dual antiplatelet therapy in the use of stent-assisted coil embolization increases the risk of intracranial hemorrhage and possibly rebleeding from a ruptured aneurysm. This heightened risk must be recognized when contemplating the appropriate therapy for a cerebral aneurysm and when considering the placement or manipulation of a ventricular catheter in a patient receiving dual antiplatelet therapy. Further study of intracranial procedures in patients receiving dual antiplatelet therapy is indicated.

THE INCOME TAX INQUIRY

Broad based bifurcation aneurysms are challenging. Various endovascular techniques aim at stabilizing the coil package in the aneurysm. Among these, the waffle cone technique provides a viable alternative to Y stenting in selected cases, incorporating a less complex delivery, and the reduced inherent risk of a single stenting procedure compared with the use of two stents in Y configuration. Unlike conventional stents, the distal end of the new pCONus device opens like a blossoming flower inside of the aneurysm to facilitate the waffle cone technique. In a case with tandem unruptured broad based middle cerebral artery bifurcation aneurysms, the complex anatomical challenge was resolved by a unique combination of both techniques: two pCONus deployed in Y configuration, offering stable neck coverage for coiling both aneurysms. The angiographic results with complete occlusion of both aneurysms and the uneventful clinical course at 90 days with continued daily administration of dual antiplatelet therapy are encouraging.