scholarly journals Effectiveness of Platelet Function Analysis-Guided Aspirin and/or Clopidogrel Therapy in Preventing Secondary Stroke: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 (12) ◽  
pp. 3907
Author(s):  
Ann-Rong Yan ◽  
Mark Naunton ◽  
Gregory M. Peterson ◽  
Israel Fernandez-Cadenas ◽  
Reza Mortazavi

Background: Antiplatelet medications such as aspirin and clopidogrel are used following thrombotic stroke or transient ischemic attack (TIA) to prevent a recurrent stroke. However, the antiplatelet treatments fail frequently, and patients experience recurrent stroke. One approach to lower the rates of recurrence may be the individualized antiplatelet therapies (antiplatelet therapy modification (ATM)) based on the results of platelet function analysis (PFA). This review was undertaken to gather and analyze the evidence about the effectiveness of such approaches. Methods: We searched Medline, CINAHL, Embase, Web of Science, and Cochrane databases up to 7 January 2020. Results: Two observational studies involving 1136 patients were included. The overall effects of PFA-based ATM on recurrent strokes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.69 to 1.58), any bleeding risk (OR 1.39; 95% CI 0.92 to 2.10) or death hazard from any cause (OR 1.19; 95% CI 0.62 to 2.29) were not significantly different from the standard antiplatelet therapy without ATM. Conclusions: The two studies showed opposite effects of PFA-guided ATM on the recurrent strokes in aspirin non-responders, leading to an insignificant difference in the subgroup meta-analysis (OR 1.59; 95% CI 0.07 to 33.77), while the rates of any bleeding events (OR 1.04; 95% CI 0.49 to 2.17) or death from any cause (OR 1.17; 95% CI 0.41 to 3.35) were not significantly different between aspirin non-responders with ATM and those without ATM. There is a need for large, randomized controlled trials which account for potential confounders such as ischemic stroke subtypes, technical variations in the testing protocols, patient adherence to therapy and pharmacogenetic differences.

Author(s):  
Ann-Rong Yan ◽  
Mark Naunton ◽  
Gregory M. Peterson ◽  
Israel Fernandez Cadenas ◽  
Reza Mortazavi

Background: Antiplatelet medications such as aspirin and clopidogrel are used following thrombotic stroke or transient ischemic attack (TIA) to prevent a recurrent stroke. However, the antiplatelet treatments fail frequently, and patients experience recurrent stroke. One approach to lower the rates of recurrence, may be the individualized antiplatelet therapies (antiplatelet therapy modification (ATM)) based on the results of platelet function analysis (PFA). This review was undertaken to gather and analyse the evidence about the effectiveness of such approaches. Methods: We searched Medline, CINAHL, Embase, Web of Science and Cochrane databases to 7 January 2020. Results: Two observational studies involving 1136 patients were included. The overall effects of PFA-based ATM on recurrent strokes (OR 1.05; 95% CI 0.69 to 1.58), any bleeding risk (OR 1.39; 95% CI 0.92 to 2.10) or death hazard from any cause (OR 1.19; 95% CI 0.62 to 2.29) were not significantly different from the standard antiplatelet therapy without ATM. Conclusions: The two studies showed opposite effects of PFA-guided ATM on the recurrent strokes in aspirin non-responders, leading to an insignificant difference in the subgroup meta-analysis (OR 1.59; 95% CI 0.07 to 33.77), while the rates of any bleeding events (OR 1.04; 95% CI 0.49 to 2.17) or death from any cause (OR 1.17; 95% CI 0.41 to 3.35) were not significantly different between aspirin non-responders with ATM and those without ATM. There is a need for large randomized controlled trials which account for potential confounders such as ischemic stroke subtypes, technical variations in the testing protocols, patient adherence to therapy, and pharmacogenetic differences.


2021 ◽  
Vol 10 (23) ◽  
pp. 5506
Author(s):  
Francesco Condello ◽  
Matteo Sturla ◽  
Riccardo Terzi ◽  
Alberto Polimeni ◽  
Giulio G. Stefanini

(1) Shorter-duration dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy has been shown to significantly reduce bleeding events while preserving anti-ischemic effects in patients undergoing conventional percutaneous coronary interventions (PCI). Whether this strategy is also safe and effective in complex PCI remains elusive; (2) A systematic search of randomized controlled trials comparing a short course of ticagrelor-based DAPT versus standard DAPT in patients undergoing complex PCI was performed; (3) Of 10,689 studies screened, 3 were identified for a total of 4176 participants on ticagrelor monotherapy after a short course of ticagrelor-based DAPT, and 4209 on standard DAPT. The pooled analysis revealed no difference in the outcomes of major bleeding, myocardial infarction, definite or probable stent thrombosis and ischemic stroke. A significant reduction in the risk of cardiovascular death (incidence rate ratio (IRR) 0.52; 95% CI 0.28–0.96; p = 0.04), all-cause death (IRR 0.65; 95% CI 0.49–0.86; p = 0.003), and any bleeding events (IRR 0.62; 95% CI 0.47–0.81; p < 0.001) was seen in the shorter DAPT group; (4) Among patients undergoing complex PCI, ticagrelor monotherapy after a short course of ticagrelor-based DAPT significantly reduced bleeding risk without increasing ischemic risk. More data are needed to definitively explain mortality benefits.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Maurizio Paciaroni ◽  
Birsen Ince ◽  
Bo Hu ◽  
Jiann-Shing Jeng ◽  
Kursad Kutluk ◽  
...  

Aim. Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population. Methods. PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals. Results. Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel (n=14,293) or aspirin (n=15,064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53–0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups. Conclusions. The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Guang Zhang ◽  
Jing-Yu Gu ◽  
Qiang-Qiang Fu ◽  
Shi-Wu Chen ◽  
Jie Xue ◽  
...  

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT).Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events.Results: Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention.Conclusions: Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Francesco Condello ◽  
Matteo Sturla ◽  
Riccardo Terzi ◽  
Alberto Polimeni ◽  
Giulio Stefanini

Abstract Aims Current guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor for 6–12 months after percutaneous coronary intervention (PCI). A shorter duration ticagrelor-based DAPT followed by ticagrelor monotherapy can significantly reduce bleeding events while preserving anti-ischaemic effects in patients undergoing conventional PCI. Whether this strategy can be safely and effectively applied to those patient that undergo ‘complex’ PCI is uncertain. Methods We performed a systematic search of randomized controlled trials comparing a short course of ticagrelor-based DAPT vs. standard DAPT in patients undergoing complex PCI. A mixed-effects Poisson regression model with random intervention effects was used to estimate the pooled incidence rate ratios (IRR) with 95% confidence intervals (CI). Results Out of 10 689 studies screened, three were identified for a total of 4176 participants on ticagrelor monotherapy after a short course of ticagrelor based DAPT, and 4209 on standard DAPT. Overall, the pooled analysis showed a strong evidence that compared to standard treatment, ticagrelor monotherapy after a short course of ticagrelor-based DAPT (1–3 months) reduced the risk of cardiovascular death [IRR 0.52; CI (0.28–0.96); P = 0.04; I2 = 0%], all-cause death [IRR 0.65; CI (0.49–0.86); P = 0.003; I2 = 0%], and any bleeding events [IRR 0.62; CI (0.47–0.81); P &lt; 0.001; I2 = 44%]. Weak evidence was found of an association between the experimental strategy and a lower risk of myocardial infarction [IRR 0.79; CI (0.61–1.01); P = 0.06; I2 = 0%]. Instead, no significant difference in the risk of major bleeding [IRR 0.72; CI (0.48–1.08); P = 0.11; I2 = 61%], definite or probable stent thrombosis [IRR 0.77; CI (0.34–1.75); P = 0.53; I2 = 0%] and ischaemic stroke [IRR 0.83; CI (0.25–2.73); P = 0.76; I2 = 0%] was observed. We speculate that the observed mortality benefits might be related to the reduction of any bleeding events, mainly dictated by minor bleeding reduction, since major bleeding did not seem to be decreased in the shorter regimen group. Conclusion Among patients undergoing complex PCI, ticagrelor monotherapy after a short course of ticagrelor-based DAPT significantly reduced bleeding risk without increasing ischaemic risk. As complex PCI procedures are being increasingly performed nowadays, and more comorbid patients are being treated, more studies are required to confirm and explain these findings. This could lead to optimization of antiplatelet therapy across a broad spectrum of patients.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 651
Author(s):  
Shih-Yi Lin ◽  
Cherry Yin-Yi Chang ◽  
Cheng-Chieh Lin ◽  
Wu-Huei Hsu ◽  
I.-Wen Liu ◽  
...  

Background: The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results: Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81; 95% CI, 0.59–1.11; I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45; 95% CI, 0.16–1.29; I2 = 4%). Conclusions: Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Lulu Zhang ◽  
Xiaowei Hu ◽  
Juehua Zhu ◽  
Xiuying Cai ◽  
Yan Kong ◽  
...  

Background. The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective. To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method. The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result. Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion. The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.


2020 ◽  
Vol 26 ◽  
pp. 107602962093520
Author(s):  
William Tappe ◽  
Saurabh Aggarwal ◽  
Ozlem Topaloglu ◽  
Massimo Iacobelli

Defibrotide is approved to treat hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) with renal/pulmonary dysfunction following hematopoietic cell transplantation (HCT) in adult and pediatric patients in the United States, and to treat severe hepatic VOD/SOS post-HCT in adult and pediatric patients aged >1 month in the European Union. The defibrotide prescribing information warns that defibrotide may increase bleeding risk in VOD/SOS patients. To broaden our understanding of the incidence of bleeding with defibrotide, we performed a meta-analysis of the published literature of defibrotide use outside of the post-HCT VOD/SOS setting. Of 1857 records identified, 125 reported on defibrotide; 23 contained data on bleeding events. The estimated overall incidence of bleeding events was 1% (95% confidence interval [CI]: 0%-2%) and 8% (95% CI: 3%-14%) in studies using intravenous defibrotide and studies with controls, respectively. The risk ratio for bleeding events with intravenous defibrotide versus controls was 0.36 (95% CI: 0.24-0.52; P < .00001) among studies with data on intravenous defibrotide and controls. This meta-analysis of defibrotide use outside of the post-HCT VOD/SOS setting suggests that the incidence of bleeding with defibrotide is lower than controls.


2020 ◽  
Vol 13 (5) ◽  
pp. 749-752
Author(s):  
Alexandru Burlacu ◽  
Adrian Covic

Abstract In this issue of Clinical Kidney Journal, Park et al. presents the results of a nationwide population-based trial that included &gt;5000 dialysis patients receiving a drug-eluting stent (DES). The main objective was to evaluate the effectiveness and the safety of prolonged dual antiplatelet therapy (DAPT). The primary outcome was a composite of mortality, non-fatal myocardial infarction, coronary revascularization and stroke, significantly lowered by a longer DAPT regimen at 12, 15 and 18 months, respectively. Longer DAPT tended to be correlated with higher bleeding events at all landmarks, with no statistical significance. An important element was that almost 75% of the index events were acute coronary syndromes. This study presents the first solid evidence for a significant benefit of prolonged DAPT in dialysis patients receiving a DES. We believe that end-stage renal disease is still in the middle of a rope game, being pulled to one side or another by other features, inclining towards a higher bleeding risk or towards higher ischaemic risk. The acute versus elective presentation seems to weigh in choosing the antiplatelet regimen. The ‘one-size-fits-all strategy’ is not suitable for this particular group. Probably in the future, practitioners will be provided with decision pathways generated by artificial intelligence algorithms yielding ‘truly individualized’ DAPT protocols for every single patient.


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