scholarly journals Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events

Stroke ◽  
2021 ◽  
Author(s):  
Alexandra Bálint ◽  
Dániel Tornyos ◽  
Oumaima El Alaoui El Abdallaoui ◽  
Péter Kupó ◽  
András Komócsi

Background and Purpose: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease. Methods: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality. Results: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P =0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]). Conclusions: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

Author(s):  
Ahmad Hazem ◽  
Sunita Sharma ◽  
Amit Sharma ◽  
Cameron Leitch ◽  
Roopalakshmi Sharadanant ◽  
...  

Importance: Up to 10% of patients with acute myocardial infarction (AMI) have right bundle branch block (RBBB), and RBBB has been associated with a higher risk of mortality. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with AMI. Acute coronary syndrome (ACS) Data Sources: We have systematically searched Ovid, Scopus and Web of Science through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts, selecting studies that described all-cause mortality or cardiovascular death in patients with RBBB and suspected ACS. We excluded studies that reported unadjusted outcomes. Knowledge synthesis: We pooled risk ratio with hazard ratio in studies reporting those outcomes. When reported, odds ratio was converted into risk ratio using reported event rate in each study’s unexposed -read: non RBBB- group. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: Eighteen studies were found that reported eligible data. All were observational studies, involving over 89,000 patients. In short-term follow up (up to 30 days), RBBB on presentation was associated with higher all-cause mortality rate, compared to patients without RBBB (RR 2.23, 95% CI 1.76-2.82). There was a trend for higher mortality at long-term follow up (range: 6 months-16 years) that did not reach statistical significance (RR 1.45, 95% CI 0.93-2.25). Figure-1 demonstrates the forest plot. Risk of bias was assessed with the Newcastle-Ottawa scale and majority of included studied were deemed moderate to high quality. Conclusion and Relevance: RBBB is associated with a more than 2-fold higher risk of all-cause mortality in patients with AMI at 30 days follow up. Patients with AMI and RBBB represent a high risk group for adverse outcomes. A sentence on the differential findings for new vs. old RBBB and association with outcomes could follow here.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michelle P Lin ◽  
Kevin M Barrett ◽  
James F Meschia ◽  
Benjamin H Eidelman ◽  
Josephine F Huang ◽  
...  

Introduction: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We conducted a systematic review and meta-analysis to estimate the comparative effectiveness and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or TIA. Hypothesis: Cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from inception to 2019. Randomized clinical trials that compared cilostazol vs aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and bleeding were included. A random-effects estimate was computed based on Mantel-Haenszel methods. The pooled estimates with 95% confidence intervals were compared between cilostazol and aspirin and displayed as forest plots (Figure). Results: The search identified 5 randomized clinical trials comparing cilostazol vs aspirin for secondary stroke prevention that enrolled 7,240 patients from primarily Asian countries (3,615 received cilostazol and 3,625 received aspirin). The pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (Hazard ratio [HR] 0.70; 95%CI, 0.54-0.89), intracranial hemorrhage (HR 0.41; 95%CI, 0.25-0.65) and bleeding (HR 0.71; 95%CI, 0.55-0.91). See forest plots. Conclusion: This meta-analysis suggests cilostazol is more effective than aspirin in the prevention of recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Confirmatory randomized trials of cilostazol for secondary stroke prevention to be performed in more generalizable populations are needed.


2019 ◽  
Vol 15 (2) ◽  
pp. 68-73
Author(s):  
ABK Bashiruddin ◽  
Mohammad Ibrahim Chowdhury ◽  
Biplob Bhattacharjee ◽  
Abul Hossen Shahin ◽  
Syed Ali Ahsan ◽  
...  

Background: Clinical guidelines recommend that optimal management of acute coronary syndrome (ACS) should include patient risk stratification. Predicting the anatomical extension of coronary artery disease (CAD) is also potentially useful for clinical decision. Objective: The objective of our study was to determine whether the TIMI risk score correlates with the angiographic extent and severity of CAD in patients with NSTE- ACS. Materials and Methods: This was a cross-sectional observational study carried out in the Department of Cardiology, Chattogram Medical College Hospital (CMCH) from September 2017 to May 2018. A total of 200 patients diagnosed with NSTE- Acute Coronary Syndrome were included as sample by purposive sampling method. TIMI risk score for each patient was calculated and the patients were stratified into 3 groups according to the TIMI risk score: low risk (0-2); intermediate risk (3-4); high risk (5-7). The severity of the CAD was assessed by Vessel score and Gensini score. Result: The mean ± SD of the age of study population was 53.7 ±10.8 years (range 37–77) and 142 (71%) were male. Regarding cardiovascular risk factors, 137 (68.5%) patients had diabetes mellitus, 83 (41.5%) had dyslipidaemia, 155 (77.5%) had hypertension, 136 (68%) were current smoker and 70 (35%) had a family history of CAD. The Gensini score was higher in patients at high risk TIMI group (p<0.001). Moreover, there was a signiûcant positive correlation between the TIMI and Gensini score (r=0.446,p<0.001). TIMI score can predict significant CAD moderately well (area under the curve 0.661, p=0.001). Patients with TIMI score > 4 were more likely to have significant three vessel CAD (65.9%) versus those with TIMI risk score 3-4 (17.9%) and TIMI risk score < 3 (2%) (p< 0.001). Conclusion: Study showed the TIMI score is significantly correlated with the extent of CAD as assessed by the Gensini score. It is accurate for predicting severe CAD among NSTE-ACS patients. University Heart Journal Vol. 15, No. 2, Jul 2019; 68-73


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingxiang Wen ◽  
Yaqi Li ◽  
Xiang Qu ◽  
Yanyan Zhu ◽  
Lingfang Tian ◽  
...  

Abstract Background This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS). Methods Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR). Results Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = − 32.26; 95% CI: − 56.48 to − 8.76; P < 0.01; VASP-PRI: WMD = − 9.61; 95% CI: − 14.63 to − 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12–0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08–1.81; P = 0.01). Conclusions Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.


2020 ◽  
Author(s):  
Xiao-Qing Quan ◽  
Run-Chang Wang ◽  
Qing Zhang ◽  
Cun-Tai Zhang ◽  
Lei Sun

Abstract Background: The association between the lymphocyte-to-monocyte ratio (LMR) and prognosis of patients with acute coronary syndrome (ACS) is not fully understood. We performed this systematic review and meta-analysis to evaluate the correlation between LMR and mortality or major adverse cardiac events (MACE) in patients with ACS. Methods: A systematic search was performed in PubMed, MEDLINE, EMBASE, the Cochrane Library, Scopus and Web of science. The association between LMR and mortality or MACE was analyzed in patients with ACS. The search was updated to April 15, 2020. Results: A total of 5 studies comprising 4343 patients were included in this meta-analysis. The results showed that lower LMR predicted short-term mortality/MACE (hazard ratio [HR] = 3.44, 95% confidence interval [CI]: 1.46–8.14, P < 0.05) and higher long-term mortality/MACE (HR = 1.70, 95% CI: 1.36– 2.13, P < 0.05). According to our subgroup analysis, there is still has a statistical significance for LMR to predict long-term mortality/MACE in any subgroups. Conclusions: This study suggested that lower LMR value might be associated with higher short-term mortality/MACE and long-term mortality/MACE in ACS patients. Especially for younger ACS patients, low LMR was more closely associated with poor prognosis.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ashkan Shoamanesh ◽  
Chun Shing Kwok ◽  
Phyo K Myint ◽  
Yoon K Loke ◽  
Hannah Copley ◽  
...  

INTRODUCTION: The predominant underlying mechanism of lacunar stroke differs from that of other ischemic stroke subtypes. Accordingly, so may the ideal stroke prevention regimen. We aimed to evaluate the efficacy of different antiplatelet agents in lacunar stroke patients. Method: We searched MEDLINE, EMBASE and the Cochrane library for RCTs that evaluated antiplatelet therapy in patients with ischemic stroke. Trials which provided stroke recurrence rates in patients presenting with lacunar stroke, or where the data was obtainable from manuscript authors were included. In addition, we included the novel SPS3 trial’s antiplatelet arm data presented at the 2011 ISC. We performed pooled analysis to assess the crude frequency of recurrent stroke and a random effects meta-analysis. Results: Lacunar stroke data was available for 12 trials encompassing 35, 218 participants (mean age 65, 65% male). The pooled crude recurrent stroke rate was least for cilostazol monotherapy (6.2%), followed by ASA monotherapy (7.4%), clopidogrel monotherapy (8.6%), ASA/dipyridamole (8.6%) and greatest for ASA/clopidogrel therapy (9.1%). Rate ratios of lacunar stroke patients suggest no significant efficacy advantage for ASA [ASA vs placebo (RR 0.72, 95% CI 0.34-1.50; p=0.38)], ASA/clopidogrel [ASA/clopidogrel vs ASA (RR 0.80, 95% CI 0.62-1.03; p=0.08), ASA/clopidogrel vs clopidogrel (RR 0.95, 95% CI 0.79-1.15; p=0.63)], sarpogrelate [sarpogrelate vs ASA (RR 1.31, 95% CI 0.84-2.04; p=0.23)] and ASA/dipyridamole [ASA/dipyridamole vs ASA (RR 0.90, 95% CI 0.70-1.16; p=0.042)] for recurrent stroke. The results from Japanese trials evaluating the efficacy of cilostazol found that it is significantly better than both placebo (RR 0.51, 95% CI 0.30-0.85; p=0.01) and ASA (RR 0.70, 95% CI 0.51-0.96; p=0.03) in the secondary prevention of stroke. Conclusions: There seems to be no significant advantage among the various antiplatelet agents studied in lacunar stroke patients apart for cilostazol. However, this requires confirmation within large randomized trials outside of Japanese populations.


2021 ◽  
pp. neurintsurg-2021-017928
Author(s):  
Jian Zhang ◽  
Shijian Chen ◽  
Shengliang Shi ◽  
Yueling Zhang ◽  
Deyan Kong ◽  
...  

ObjectiveIn this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO).MethodsWe searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration.ResultsWe included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0–2, mRS scores 0–1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy.ConclusionCompared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS.Trail registration numberPROSPERO: CRD42021236691.


2018 ◽  
Vol 118 (10) ◽  
pp. 1839-1846 ◽  
Author(s):  
Laurent Bonello ◽  
Marc Laine ◽  
Gilles Lemesle ◽  
Etienne Puymirat ◽  
Thibaut Dabry ◽  
...  

Background The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk–benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown. Objective We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS. Methods We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings. Results We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies (n = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79–0.99; p = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95–1.27; p = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77–0.93; p < 0.001), including a reduction in mortality (pHR = 0.82) (95% CI: 0.7–0.96; p = 0.016). Conclusion Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.


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