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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes and bleeding definitions are compared. The HAS-BLED risk score is recommended in patients with AF and in ACS patients with AF. In patients with ACS with or without a stent dual antiplatelet therapy with a P2Y12 receptor antagonist and acetylsalicylic acid (ASA) is recommended for 12 months, preferable with prasugrel or ticagrelor unless there is an additional indication of warfarin or increased risk of bleeding. In patients with AF, warfarin is recommended if the risk of stroke is moderate to high, but newer emerging antithrombotic drugs will be recommended along with/or preferred to warfarin in the nearby future. Patients with CVD (without cardiogenic causes) are recommended clopidogrel treatment for secondary prevention, where as patients with PAD are recommended ASA or clopidogrel. With future implementation of new antithrombotic treatment regimens as monotherapy and in combinations with antiplatelet therapy, increased focus on risk of thromboembolic events and bleeding and individual tailoring of antithrombotic therapy is warranted.
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PMID:Risk of bleeding related to antithrombotic treatment in cardiovascular disease. 2272 19

Stroke and myocardial infarction are leading causes of death and disability worldwide. Typically, these events are triggered by the rupture or erosion of "vulnerable" atherosclerotic plaque, a phenomenon termed atherothrombosis.Three platelet activation pathways are presumed to be particularly important in the genesis of atherothrombosis and are triggered by 1) cyclo-oxygenase (COX)-1 mediated thromboxane A2 (TXA2) synthesis and activation via the TXA2 receptor, 2) adenosine diphosphate (ADP) via the P2Y12 receptor, and 3) thrombin via the protease activated receptor (PAR)-1.Despite the efficacy of aspirin and of a growing family of P2Y12 receptor antagonists on the first 2 pathways, major cardiovascular events continue to occur in patients with coronary and cerebrovascular disease, suggesting that thrombin-mediated platelet activation may contribute to these adverse events.Recently, a novel class of antiplatelet agents able to inhibit thrombin-mediated platelet activation has been developed, PAR-1 inhibitors. In this chapter, we will discuss the rationale underlying the development of this novel class of agents focus on the two drugs in the most advanced stages of development: vorapaxar (SCH530348) and atopaxar (E5555).
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PMID:PAR-1 inhibitors: a novel class of antiplatelet agents for the treatment of patients with atherothrombosis. 2291 34

Dual antiplatelet therapy with clopidogrel combined with aspirin reduces ischemic events in acute coronary syndromes (ACS). The individual response to clopidogrel is, however, very variable from one subject to another, and the risk of events seems higher when platelet inhibition is insufficient. Ticagrelor is a potent oral inhibitor of platelet activity. It binds reversibly to the P2Y12 adenosine diphosphate. The platelet inhibition that it induces is faster and more pronounced than that of clopidogrel. In patients who have an ACS (PLATO study) with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke, without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. In Belgium, Brilique is currently indicated in combination with aspirin for the prevention of atherothrombotic events in patients with ACS.
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PMID:[Medication of the month. Ticagrelor (Brilique): potent oral antagonist of platelet activity]. 2311 50

The concomitant use of aspirin and an ADP receptor (P2Y12) blocker, also known as dual antiplatelet therapy (DAPT), has been extensively investigated as a primary and secondary prevention strategy in an effort to reduce the risk of cardiovascular events. In this manuscript the authors review the current guideline recommendations for DAPT and discuss the scientific data that supports these recommendations. Reported are also the scientific knowledge gaps and how future studies are likely to delineate these issues. Incremental knowledge is not likely to be an alternative to individualized care provided by the astute clinician to his patient. In consideration for prescribing DAPT (drug, dosage and duration) the clinician will have to weigh the potential benefits (reduction in death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) and risks (severe or life-threatening bleeding) for each and every patient.
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PMID:Dual antiplatelet therapy for primary and secondary prevention. 2314 38

Dilating HIV vasculopathy can be a cause of ischemic and hemorrhagic stroke in patients with HIV. Although first identified in children, this condition is increasingly being recognized in adults and has a dismal natural history under medical or expectant management. Vessel wall invasion by varicella zoster virus, HIV or Mycobacterium avium intracellulare complex (MAI) has been postulated as a possible etiology. We present a case of an adult patient with HIV and chronic disseminated MAI infection who presented with ischemic stroke and three fusiform cerebral aneurysms that were successfully treated with the pipeline embolization device (PED). Flow diversion may be a viable treatment option for patients presenting with this serious neurovascular condition when aneurysm location precludes parent vessel sacrifice or surgical bypass. In addition, platelet function testing with VerifyNow may be valuable in selecting the appropriate P2Y12 receptor antagonist to be used in order to prevent PED thrombosis, since some of the antiretroviral drugs may inhibit clopidogrel or prasugrel metabolism.
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PMID:Successful endovascular treatment of three fusiform cerebral aneurysms with the Pipeline Embolization Device in a patient with dilating HIV vasculopathy. 2340 Aug 1

Dilating HIV vasculopathy can be a cause of ischemic and hemorrhagic stroke in patients with HIV. Although first identified in children, this condition is increasingly being recognized in adults and has a dismal natural history under medical or expectant management. Vessel wall invasion by varicella zoster virus, HIV or Mycobacterium avium intracellulare complex (MAI) has been postulated as a possible etiology. We present a case of an adult patient with HIV and chronic disseminated MAI infection who presented with ischemic stroke and three fusiform cerebral aneurysms that were successfully treated with the pipeline embolization device (PED). Flow diversion may be a viable treatment option for patients presenting with this serious neurovascular condition when aneurysm location precludes parent vessel sacrifice or surgical bypass. In addition, platelet function testing with VerifyNow may be valuable in selecting the appropriate P2Y12 receptor antagonist to be used in order to prevent PED thrombosis, since some of the antiretroviral drugs may inhibit clopidogrel or prasugrel metabolism.
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PMID:Successful endovascular treatment of three fusiform cerebral aneurysms with the Pipeline Embolization Device in a patient with dilating HIV vasculopathy. 2341 Jul 17

Platelets are the key in the pathogenesis of atherothrombotic disease such as acute coronary syndromes, stroke, and peripheral arterial disease. Current anti-platelet treatments are mainly based on inhibition of two important pathways of platelet activation: thromboxane A2 (TXA2) mediated (aspirin) and adenosine diphosphate (ADP)-P2Y12 receptor mediated (clopidogrel, prasugrel, and ticagrelor). Despite the dual anti-platelet therapy with aspirin and P2Y12 inhibitors have reduced ischemic events in patients with acute coronary syndromes (ACS), the rate of recurrent ischemic complication after ACS remains high. Combination of multiple anti-platelet agents is also associated with increased risk of bleeding. Thrombin is a potent platelet agonist and the increase of its activity has been reported in patients with ACS. Platelet effects of thrombin are mediated by protease-activated receptors (PAR), and PAR-1 is the most important receptor in human platelets. Two PAR-1 antagonists, vorapaxar and atopaxar, have undergone clinical investigation. In this review, we will describe the pharmacology of PAR-1 antagonists and will review and discuss results of randomized clinical trials with PAR-1 antagonists.
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PMID:Novel anti-platelet agents: focus on thrombin receptor antagonists. 2343 63

The novel oral P2Y12 inhibitors (prasugrel and ticagrelor) have been incorporated into the recently updated acute coronary syndrome (ACS) guidelines, as an adjunct antiplatelet treatment to aspirin. The studies involving the use of new oral antiplatelet agents that are more potent, predictable and faster platelet inhibitors than clopidogrel have demonstrated superiority with respect to the primary composite endpoint (cardiovascular death, non-lethal myocardial infarction, stroke) for both prasugrel and ticagrelor compared to clopidogrel. The subgroup analysis of the relevant studies showed that these new agents differ in their level of efficacy in different ACS patient subgroups: (1) Mortality was reduced with ticagrelor; (2) Ticagrelor is especially more effective in intermediate-and high-risk non-ST elevation ACS patients in whom early invasive strategy is selected; (3) Prasugrel should be especially preferred in patients with acute ST elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) after diagnostic angiography; and (4) Prasugrel is more effective in diabetic patients. While clopidogrel is recommended for ACS patients who are followed with a non-invasive strategy or who have not undergone percutaneous revascularization, it is the last line choice or an alternative to the P2Y12 inhibitor therapy for patients undergoing invasive strategy.
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PMID:[Prominent features of management strategies in acute coronary syndromes with the new oral antiplatelet agents]. 2366 8

Rivaroxaban is a factor Xa inhibitor that was recently reviewed by the Food and Drug Administration as a potential therapy to reduce the risk of recurrent atherothrombotic events in patients with acute coronary syndromes. Approval of this drug would represent a paradigm shift away from dual antiplatelet therapy toward long-term triple antithrombotic therapy. However, to date, no other experimental anticoagulant agent has demonstrated a favorable risk-benefit profile in this population, in part because of the expected increased risk in major bleeding by combining aspirin, a P2Y12 receptor inhibitor, and an anticoagulant. Approvability of rivaroxaban was considered largely on the basis of the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51) trial, which demonstrated a significant reduction in a composite of cardiovascular death, myocardial infarction, and stroke. Although the primary efficacy endpoint was met, a substantial amount of missing data was observed. We discuss the impact of missing data in this trial, its implications for informative censoring of safety events (major bleeding), and implications for future cardiovascular outcomes trials.
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PMID:The ATLAS ACS 2-TIMI 51 trial and the burden of missing data: (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51). 2374 77

Randomized controlled trials have demonstrated benefits from antithrombotic therapies for coronary artery disease (primary prevention, stable coronary artery disease, acute coronary syndromes, and percutaneous intervention) and for atrial fibrillation. The regimens with the optimal balance of efficacy and safety with coronary artery disease depend on the particular clinical manifestation, with atrial fibrillation on the risk of stroke, and with both conditions on the competing risk of major bleeding with the chosen antithrombotic therapy. The antithrombotic agents include aspirin, P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) and oral anticoagulants (warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, and apixaban). Atrial fibrillation and coronary artery disease often occur in the same patient and require decisions as to what individual or combination of antithrombotic therapies are necessary to provide optimal protection against coronary events and stroke, and cause as little bleeding as possible. Practice guidelines now recommend oral anticoagulant therapy for most patients with atrial fibrillation and consideration of "triple therapy" (oral anticoagulant and aspirin and clopidogrel) when there is a concomitant acute coronary syndrome or stent placement, though acknowledging the risks of major bleeding. In the absence of definitive trials of combination therapies, such practice guidelines are based on extrapolations from randomized trials and observational data.
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PMID:Oral antithrombotic therapy in atrial fibrillation associated with acute or chronic coronary artery disease. 2379 Jun


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