Antiplatelet Therapy as a Risk Factor for Microbleeds in Intracerebral Hemorrhage Patients: Analysis Using Specific Antiplatelet Agents

Introduction: Antiplatelet agents are usually discontinued to reduce hemorrhagic tendency during the acute phase of intracerebral hemorrhage (ICH). However, their use after ICH remains controversial. Methods: This study investigated the effect of antiplatelet agents in ICH survivors. We used the National Health Insurance Service-National Sample Cohort 2002–2013 database for retrospective cohort modeling, estimating the effects of antiplatelet therapy on clinical events. Subgroup analyses assessed antiplatelet medication administered before ICH. Results: The prescription rate of antiplatelets after ICH was also examined. Of 1,007 ICH-surviving patients, 303 subsequent clinical events were recorded, 41 recurrences of nonfatal ICH recurrence, 26 incidents of nonfatal ischemic stroke, 6 nonfatal myocardial infarctions, and 230 incidents of all-cause mortality. The use of antiplatelet therapy significantly decreased the risk of primary outcomes (adjusted hazard ratio [AHR] = 0.743, 95% confidence interval [CI] = 0.578–0.956) and all-cause mortality (AHR = 0.740, 95% CI = 0.552–0.991), especially in patients without a history of antiplatelet treatment. The use of antiplatelet medication after ICH did not significantly increase the recurrence of ICH. The prescription rate of antiplatelet therapy within 1 year was 16.6%. Among 220 patients with a history of using antiplatelet medication, the resumption rate was 0.5% at discharge, 5% after a month, 12.7% after 3 months, and 29.1% after a year. Conclusion: Using antiplatelet treatment after ICH does not increase chances of recurrence, but lowers the occurrence of subsequent clinical events, especially mortality. However, the prescription and resumption rate of antiplatelet therapy after ICH remains low in South Korea.

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Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications?

Medicina ◽

10.3390/medicina57040357 ◽

2021 ◽

Vol 57 (4) ◽

pp. 357

Author(s):

Gabriele Savioli ◽

Iride Francesca Ceresa ◽

Sabino Luzzi ◽

Alice Giotta Lucifero ◽

Maria Serena Pioli Di Marco ◽

...

Keyword(s):

Risk Factor ◽

Antiplatelet Therapy ◽

Head Trauma ◽

Clinical Condition ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Control Group ◽

Risk Of Bleeding ◽

Level Ii ◽

Single Center Study

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.

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Abstract WP368: The Association of Prior Use of Antiplatelet Agents and Increased Mortality and Morbidity in Intracerebral Hemorrhage Patients

Stroke ◽

10.1161/str.48.suppl_1.wp368 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Nadeem Khan ◽

Fazeel Siddiqui ◽

Joshua Goldstein ◽

Ying Xian ◽

Margueritte Cox ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Antiplatelet Therapy ◽

Antiplatelet Agents ◽

Mortality And Morbidity ◽

Significant Difference ◽

Prior Use ◽

History Of ◽

Artery Disease ◽

Ischemic Attack

Introduction: Use of anti-platelet therapy is common among patients presenting with intracerebral hemorrhage (ICH). There are limited data regarding pre-stroke antiplatelet therapy (APT) and outcomes in patients presenting with spontaneous ICH. We hypothesized that prior use of antiplatelet agents increases mortality and discharge morbidity in ICH patients. Methods: We analyzed data of 82,576 ICH patients not on anticoagulation from 2185 GWTG-Stroke hospitals between Oct 2012 and March 2016. Patients were categorized as no APT, single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT). Logistic regression using generalized estimating equations to account for within-site correlations were used to assess the relationship between outcomes and prior-APT use. Results: No pre-ICH APT was used in 65.8%, SAPT in 29.5%, and DAPT in 4.8%. The median age of the cohort was 69 years and prevalence of females in the cohort was 48.6%, with preponderance of white race (58.9%). Overall onset of symptoms to arrival time was 131 minutes with a median NIHSS of 9. A total of 23.7% had history of previous stroke/transient ischemic attack, 15.3% had prior myocardial infarction/coronary artery disease and 73.4% had known hypertension. There was no significant difference in in-hospital mortality among patients not on any APT vs patients on SAPT. However, in-hospital mortality was higher among ICH patients on DAPT compared with no therapy (adjusted OR 1.41, 95 % CI 1.31-1.51, P<0.0001). Conclusion: Our study suggests that patients on DAPT, but not on SAPT, have higher mortality rates after ICH compared with patients on no APT.

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Secondary Stroke Prevention, and the Role of Antiplatelet Therapies

Clinical Medicine Therapeutics ◽

10.4137/cmt.s2208 ◽

2009 ◽

Vol 1 ◽

pp. CMT.S2208

Author(s):

Howard S. Kirshner

Keyword(s):

Risk Factor ◽

Antiplatelet Therapy ◽

Stroke Prevention ◽

Extended Release ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Internal Carotid Artery Stenosis ◽

Secondary Stroke Prevention ◽

First Line

This review considers treatments of proved efficacy in secondary stroke prevention, with an emphasis on antiplatelet therapy. Most strokes could be prevented, if readily available lifestyle and risk factor modifications could be applied to everyone. In secondary stroke prevention, the same lifestyle and risk factor modifications are also important, along with anticoagulation for patients with cardiac sources of embolus, carotid procedures for patients with significant internal carotid artery stenosis, and antiplatelet therapy. For patients with noncardioembolic ischemic strokes, FDA-approved antiplatelet agents are recommended and preferred over anticoagulants. ASA, clopidogrel, and ASA + ER-DP are recognized as accepted first-line options for secondary prevention of noncardioembolic ischemic stroke. Combined antiplatelet therapy with ASA + clopidogrel has not been shown to carry benefit greater than risk in stroke or TIA patients. Aspirin and extended release dipyridamole appeared to carry a greater benefit over aspirin alone in individual studies, leading to a recommendation of this agent in the AHA guidelines, but the recently completed PRoFESS trial showed no difference in efficacy between clopidogrel and aspirin with extended release dipyridamole, and clopidogrel had better tolerability and reduced bleeding risk.

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Abstract W P155: Antiplatelet Therapy Benefit in Secondary Stroke Prevention in Patients With Suboptimally Controlled Treatable Cerebrovascular Risk Factors

Stroke ◽

10.1161/str.45.suppl_1.wp155 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Muhammad Umer ◽

Kateryna Kurako ◽

Nestor Galvez-Jimenez ◽

Efrain Salgado

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Antiplatelet Therapy ◽

Stroke Prevention ◽

Antiplatelet Agents ◽

Large Artery ◽

Secondary Stroke Prevention ◽

Risk Factor Control ◽

Cerebrovascular Risk Factors ◽

Cerebrovascular Risk

Objective: To assess the impact of antiplatelet therapy for secondary stroke prevention in patients with suboptimally controlled treatable cerebrovascular risk factors per guidelines. Results: Of the 1755 patients, 219 (12.47%) patients had a second stroke event between November 2006-December 2012. Mean age of this group of patients was 66.4 years old with male predominance (M:F=1.5:1). 192 (88%) patients were on antiplatelet therapy at the time of the second stroke. 27 (12 %) were not on antiplatelet therapy. Of the total cohort, treatable risk factors were poorly controlled in 130 (59%) patients: 121 (55%) hypertension; 78 (36%) hyperlipidemia, 44 (20%) diabetes. Antiplatelet agents included aspirin, clopidogrel alone or in combination with aspirin, and extended-release dipyridamole. The data showed no significant difference among antiplatelet agents for secondary stroke prevention (p<0.05). Stroke classification was as follows: 162 (74%) ischemic and 57 (26%) hemorrhagic. Categories of ischemic stroke were as follows: large-artery atherosclerosis 40 (18%), small vessel disease 45 (21%), cardioembolic 42 (19%), 35 (16%) cryptogenic / stroke of undetermined etiology. Of the 192 patients on antiplatelet therapy with stroke, 116 (60%) had poorly controlled risk factors. Conclusions: This study suggests that the use of antiplatelet therapy, regardless of which agent, for secondary stroke prevention may not be important or beneficial in the absence of optimal treatable cerebrovascular risk factor control. Further studies are needed to support this finding including further analysis of our data to assess risk factor control in those patients on antiplatelet therapy who did not suffer a second stroke during the period of surveillance

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Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention

Medicina ◽

10.3390/medicina57010059 ◽

2021 ◽

Vol 57 (1) ◽

pp. 59

Author(s):

Adam Wiśniewski

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Antiplatelet Therapy ◽

Negative Impact ◽

Platelet Reactivity ◽

Antiplatelet Agent ◽

Biological Response ◽

Antiplatelet Agents ◽

Platelet Inhibition ◽

High Risk Group

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.

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Advances in Antiplatelet Therapy for Dentofacial Surgery Patients: Focus on Past and Present Strategies

Materials ◽

10.3390/ma12091524 ◽

2019 ◽

Vol 12 (9) ◽

pp. 1524 ◽

Cited By ~ 16

Author(s):

Gabriele Cervino ◽

Luca Fiorillo ◽

Ines Paola Monte ◽

Rosa De Stefano ◽

Luigi Laino ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Oral Surgery ◽

Case Reports ◽

Case Series ◽

Antiplatelet Agents ◽

Preventive Therapy ◽

Antiplatelet Drugs ◽

Risk Of Bleeding ◽

The Past ◽

Increased Risk

Background: Nowadays, patients involved in antiplatelet therapy required special attention during oral surgery procedures, due to the antiplatelet drugs assumption. The motivations of the assumption may be different and related to the patient’s different systemic condition. For this reason, accordingly to the current international guidelines, different protocols can be followed. The aim of this work is to analyze how the dentist’s approach to these patients has changed from the past to the present, evaluating the risk exposure for the patients. Methods: This review paper considered different published papers in literature through quoted scientific channels, going in search of “ancient” works in such a way as to highlight the differences in the protocols undertaken. The analyzed manuscripts are in the English language, taking into consideration reviews, case reports, and case series in such a way as to extrapolate a sufficient amount of data and for evaluating the past therapeutic approaches compared to those of today. Results: Colleagues in the past preferred to subject patients to substitution therapy with low molecular weight anticoagulants, by suspending antiplatelet agents to treatment patients, often for an arbitrary number of days. The new guidelines clarify everything, without highlighting an increased risk of bleeding during simple oral surgery in patients undergoing antiplatelet therapy. Conclusion: Either patients take these medications for different reasons, because of cardiovascular pathologies, recent cardiovascular events, or even for simple prevention, although the latest research shows that there is no decrease of cardiovascular accidents in patients who carry out preventive therapy. Surely, it will be at the expense of the doctor to assess the patient’s situation and risk according to the guidelines. For simple oral surgery, it is not necessary to stop therapy with antiplatelet agents because the risk of bleeding has not increased, and is localized to a post-extraction alveolus or to an implant preparation, compared to patients who do not carry out this therapy. From an analysis of the results it emerges that the substitutive therapy should no longer be performed and that it is possible to perform oral surgery safely in patients who take antiplatelet drugs, after a thorough medical history. Furthermore, by suspending therapy, we expose our patients to more serious risks, concerning their main pathology, where present.

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Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis

Surgical Endoscopy ◽

10.1007/s00464-021-08975-0 ◽

2022 ◽

Author(s):

Marco Valvano ◽

Stefano Fabiani ◽

Marco Magistroni ◽

Antonio Mancusi ◽

Salvatore Longo ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Meta Analysis ◽

Antiplatelet Agents ◽

Disease Recurrence ◽

Major Adverse Cardiovascular Events ◽

Control Group ◽

P2y12 Inhibitors ◽

Randomized Controlled ◽

Electronic Search ◽

Increased Risk

Abstract Background It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. Methods A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. Results Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37–3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40–14.00) and delayed PPB (OR 10.80; CI 4.63–25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. Conclusions Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

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Clopidogrel Resistance: Current Issues

Journal of Enam Medical College ◽

10.3329/jemc.v6i1.26381 ◽

2016 ◽

Vol 6 (1) ◽

pp. 38-46

Author(s):

NS Neki

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Ex Vivo ◽

Platelet Reactivity ◽

Antiplatelet Agents ◽

Clinical Problem ◽

Coronary Intervention ◽

Platelet Activity ◽

Clopidogrel Resistance ◽

Underlying Mechanisms

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

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Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study

Cerebrovascular Diseases ◽

10.1159/000492728 ◽

2018 ◽

Vol 46 (3-4) ◽

pp. 116-122

Author(s):

Yoshitaka Yamaguchi ◽

Masatoshi Koga ◽

Shoichiro Sato ◽

Hiroshi Yamagami ◽

Kenichi Todo ◽

...

Keyword(s):

Blood Pressure ◽

Risk Factor ◽

Intracerebral Hemorrhage ◽

Acute Management ◽

Acute Hypertension ◽

Risk Factor Assessment ◽

Significant Difference ◽

Pressure Lowering ◽

Hematoma Growth ◽

Multicenter Prospective Observational Study

Background: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. Results: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038–0.867; p = 0.032). Conclusions: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

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