Medications and aspirins as prevention
Introduction
Effectiveness of clopidogrel and aspirin versus aspirin in the prevention of stroke and its hemorrhagic risks. The stroke is currently the most frequent neurological pathology;In addition, to generate an important disability and serious long -term consequences for both the patient and his family. Objective: Analyze updated information on the effectiveness of the administration of clopidogrel and aspirin versus aspirin in the prevention of recurrent stroke and its risk in the development of a hemorrhagic event. METHODS: A bibliographic search for 15 systematic revisions was performed.
Developing
The published clinical trials on the joint use of clopidogrel and aspirin in the prevention of recurrent stroke and its possible hemorrhagic risks;Sources such as: the New England Journal of Medicine (NEJM), Cochrane, Nature, Pubmed, Medline and Google Scholar. Results: The studies analyzed determine that Clopidogrel and aspirin antiaggregant therapy can reduce the recurrent stroke rate by up to 71% and increase the risk of hemorrhage by 57%. Conclusion: Dual clopidogrel therapy more aspirin compared to the individualized aspirin administration.
It turned out to be more effective in prevention of recurrent vascular accident, however there is no difference significantly in terms of hemorrhagic risks. Keywords: stroke, aspirin, clopidogrel. The stroke (stroke) constitutes the most frequent neurological pathology worldwide;responsible for generating significant disabilities and serious long -term consequences for both the patient and his family. Currently, stroke is presented with an incidence of around 200 cases per 100,000 inhabitants, and a prevalence of 600 cases per 100,000 inhabitants.
According to data presented by WHO, in 2015 there were more than 6 million deaths from stroke worldwide. At the national level, a study called “Mortality by cerebrovascular diseases in Ecuador was conducted, based on records obtained from the National Institute of Statistics and Census (INEC), it was possible to determine the rates of ACV mortality adjusted by age, which descended from 66, 1% to 57.4% per 100,000 inhabitants in those 14 years. On the other hand, according to INEC data, in Ecuador for 2014, the stroke constituted the third cause of death of that year,
Behind the ischemic diseases of the heart and diabetes mellitus. With 3777 deceased people corresponding to 23.17% of the total deaths of 2014. For 2016 according to data from the Death Registry published by the INEC, 7.01% of women and 5.81% of men died from ACV. Mechanism of action of aspirin and clopidogrel. The processes involved in thrombus formation are mediated by oxygenated metabolites mainly from arachidonic acid, as well as other polyunsaturated fatty acids. The role that these metabolites play is the pillar to understand the effects of most therapeutic agents.
The platelet aggregation begins from a series of reactions where the transcendental enzyme is the cyclooxygenase or also known for its abbreviations as COX-1, where thromboxan A2, is the main product of this enzyme, responsible for stimulating aggregationof platelets. This araquidonic product causes platelets to alter morphology, release their granules and thus mediate aggregation. The salicylic acetyl acid from the acetylation of a remaining serine. In this way the platelets become unable to synthesize new proteins, thus preventing aggregation.
This enzyme is permanent inhibited, and it will be present throughout the half -life of that platelet, that is, approximately 7 – 10 days. Repeated dose of salicylic acetyl acid generates a cumulative effect on the function of platelets, thus reducing the possibility of thrombus formation. The necessary dose for the total inactivation of COX-1, is 75 mg per day of aspirin. Multiple randomized clinical trials establish their effectiveness as an antithrombotic drug at a dose between 50-320 mg/day. Higher doses do not generate greater efficacy, and the risk is more latent, inhibiting the release of prostacicclines.
In addition to increasing the danger of toxicity, especially hemorrhages. The platelets present is their surface two purinergic type receptors, the P2Y1 and P2y12, receptors coupled to G protein for diphosphate adenosin (ADP). The P2y12 is coupled to a GI protein and, when activated by the ADP inhibits the adenyl cyclasa, thus reducing the level of adenosin cyclic monophosphate (AMPC), which results in the reduction in the activation of the PLA -dependent platelets. Multiple studies conclude, that the platelet activation occurs, the two receivers must be activated, but to block the aggregation, only one of the two is required.
The clopidogrel is a drug that metabolizes in the liver, through the isoenzyme CYP2C19 of the cytochrome P450, and its active metabolite is responsible for its antiaggregant effect. Clopidogrel is an irreversible inhibitor of P2Y12 receptors, its effect is more powerful and its adverse effects are lower than other similar drugs such as ticlopidine. The usual dose is 75mg/day, with the possibility of using a load dose of 300 or 600 mg, the same that reaches a maximum concentration at two hours of the administration. There is a variability in clopidogrel’s ability to inhibit ADP -induced platelet aggregation among individuals.
And some have been established as resistant to the antiplatelet effects of this drug. Several studies promote that combined platelet antiaggregate therapy and aspirin could reduce the recurrent stroke rate, so the present review aims to analyze whether dual therapy with these antiagregants is more effective than individualized aspirin administration in thePrevention of recurrent vascular accident, while it is intended to evaluate the risk of hemorrhagic events between these two treatments.
Material and Methods: A systematic review of documents of scientific societies dedicated to health, as well as systematic reviews, multicenter studies, clinical trials and books was carried out. Search strategy: A bibliographic search was carried out in the database of scientific societies and associations of professionals from the health area such as: New England Journal of Medicine, Nature, Pubmed, Medline and Google Scholar, including information both in English in EnglishAs Spanish, with a publication date not exceeding 5 years, in the international context on clopidogrel and aspirin versus aspirin for the prevention of a recurrent stroke.
The algorithm used for the systematic search for evidence were keywords such as: ‘acetylsalicylic acid’, ‘Clopidogrel’, ‘Stroke’, ’Acute’, ‘Use’, expressed in both English and Spanish. Inclusion and exclusion criteria: The search for literature included: documents that are related to clopidogrel and aspirin compared to the use of aspirin in the preventive treatment of recurrent stroke. Studies with publication date of the last 5 years. Exclusion criteria: Studies on the use of clopidogrel and aspirin for the treatment of other unrelated pathologies.
Studies on clopidogrel administration More aspirin compared to another pharmacological treatment that is not aspirin in the prevention of recurrent stroke. Data extraction: After the initial search, 30 studies were located, although 10 were excluded that were not relevant to the objective of this review, 7 articles because they exceeded the 5 years of being published and 3 articles because they lacked information. Finally, 15 articles were selected, in which it provided information regarding the topic. 30 identified articles. 10 articles were ruled out because they were not relevant to the objective of this review.
7 articles deleted because they did not meet the criterion of maximum 5 years of publication. 3 articles deleted because they did not present the necessary information. 15 documents reviewed and included. Finally 15 articles were selected. The analyzed information was structured in order to evaluate the effectiveness of aspirin with clopidogrel versus aspirin as essential drugs to prevent a recurring stroke. The results collected from the different analyzes detail: according to the systematic review carried out by the Tergue Group of Argentina published in Pubmed.
It determines that clopidogrel plus aspirin reduces the risk of recurrence of stroke 7 to 36 patients but every 1000 patients and probably increase the risk of bleeding in 3 more patients for every 1000 treaties the same ones who will present a higher hemorrhagic event. A randomized, double blind trial published in Pubmed, analyzed 5170 patients, where stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, compared to 362 (14%) patients in the aspirin group (p = 0.006). Moderate or severe bleeding occurred in 7 (0.3%).
conclusion
Patients in the clopidogrel-aspirin group and at 9 (0.4%) patients in the aspirin group (p = 0.44). The analysis of the subgroups of the Chance Test, published in Pubmed Central, had 1,089 patients included in the current analysis, of which 481 (44.2%) had carotid or intracranial arterial stenosis (icas) and 608 (55.8%) did not have Ica. Of the 1,089 patients, 531 (48.8%) and 558 (51.2%), respectively, were assigned to receive clopidogrel-aspirin and placebo-aspirin. ICAS patients had higher rates of recurrent stroke in relation to patients without icas with 12.5% vs 5.4% respectively.
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