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Stroke Jul 2024It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection.
METHODS
The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks.
RESULTS
We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; =0.02; I=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; =0.03, I=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants.
CONCLUSIONS
In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.
Topics: Humans; Platelet Aggregation Inhibitors; Anticoagulants; Vertebral Artery Dissection; Ischemic Stroke; Stroke; Carotid Artery, Internal, Dissection
PubMed: 38847098
DOI: 10.1161/STROKEAHA.124.047310 -
Drugs Jun 2024Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1-3 months [short-term], 6 months [mid-term], and >12 months [extended] vs. 12 months).
METHODS
We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis.
RESULTS
Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02-1.28]) and bleeding (1.13 [1.00-1.28]), but not NACCE (1.12 [0.96-1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent (1.11 [1.03-1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01-2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83-1.10; and 0.96 [0.80-1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91-1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17-1.09]).
CONCLUSIONS
Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI.
CLINICAL TRIALS REGISTRATION
PROSPERO ID: CRD42021278663.
Topics: Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Female; Male; Dual Anti-Platelet Therapy; Hemorrhage; Sex Factors; Network Meta-Analysis; Clopidogrel; Treatment Outcome
PubMed: 38809372
DOI: 10.1007/s40265-024-02034-3 -
Brain and Behavior May 2024One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of desmopressin (DDAVP) in preventing hematoma expansion in intracranial hemorrhage associated with antiplatelet drugs use: A systematic review and metaanalysis.
INTRODUCTION
One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic antidiuretic hormone (ADH) analog. It has been linked to improving patient outcomes in antiplatelet-induced intracranial hemorrhage. The secondary outcomes included the incidence of thrombotic complications and neurological outcomes.
METHODS
A systematic search was conducted on three databases (PubMed, Cochrane, and ClinicalTrials.gov) to find eligible literature that compares desmopressin (DDAVP) versus controls in patients with AA-ICH. The Mantel-Haenszel statistic was used to determine an overall effect estimate for each outcome by calculating the risk ratios and 95% confidence intervals (CI). Heterogeneity was measured using the I test. The risk of bias in studies was calculated using the New Castle Ottowa Scale.
RESULTS
Five studies were included in the analysis with a total of 598 patients. DDAVP was associated with a nonsignificant decrease in the risk of hematoma expansion (RR = .8, 95% CI,.51-1.24; p = .31, I = 44%). It was also associated with a non-significant decrease in the risk of thrombotic events (RR,.83; 95% CI,.25-2.76; p = .76, I = 30%). However, patients in the DDAVP group demonstrated a significant increase in the risk of poor neurological outcomes (RR, 1.31; 95% CI, 1.07-1.61; p = .01, I = 0%). The risk of bias assessment showed a moderate to low level of risk.
CONCLUSION
DDAVP was associated with a nonsignificant decrease in hematoma expansion and thrombotic events. However, it was also associated with a significantly poor neurological outcome in the patients. Thus, until more robust clinical trials are conducted, the use of DDAVP should be considered on a case-to-case basis.
Topics: Deamino Arginine Vasopressin; Humans; Platelet Aggregation Inhibitors; Intracranial Hemorrhages; Hematoma; Hemostatics
PubMed: 38778788
DOI: 10.1002/brb3.3540 -
Journal of Artificial Organs : the... May 2024Preclinical testing using animal models is indispensable in cardiovascular research. However, the translation to clinical practice of these animal models is questionable... (Review)
Review
Preclinical testing using animal models is indispensable in cardiovascular research. However, the translation to clinical practice of these animal models is questionable since it is not always clear how representative they are. This systematic review intends to summarize the interspecies differences in the coagulation profile of animal models used in cardiovascular research. It aims to guide future research in choosing the optimal animal species. A literature search of PubMed, Embase, Web of Science (Core Collection) and Cochrane Library was performed using a search string that was well defined and not modified during the study. An overview of the search terms used in each database can be found in the appendix. Articles describing coagulation systems in large animals were included. We identified 30 eligible studies of which 15 were included. Compared to humans, sheep demonstrated a less active external pathway of coagulation. Sheep had a higher platelet count but the platelet activatability and response to biomaterials were lower. Both sheep and pigs displayed no big differences in the internal coagulation system compared to humans. Pigs showed results very similar to those of humans, with the exception of a higher platelet count and stronger platelet aggregation in pigs. Coagulation profiles of different species used for preclinical testing show strong variation. Adequate knowledge of these differences is key in the selection of the appropriate species for preclinical cardiovascular research. Future thrombogenicity research should compare sheep to pig in an identical experimental setup.
PubMed: 38769278
DOI: 10.1007/s10047-024-01446-y -
Current Problems in Cardiology Aug 2024Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months.
METHODS
Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).
RESULTS
Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.
CONCLUSIONS
In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.
Topics: Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Purinergic P2Y Receptor Antagonists; Coronary Artery Disease; Platelet Aggregation Inhibitors; Treatment Outcome; Dual Anti-Platelet Therapy; Ticagrelor
PubMed: 38750991
DOI: 10.1016/j.cpcardiol.2024.102635 -
Journal of the American Heart... May 2024There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment.
METHODS AND RESULTS
Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; =0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; =0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; =0.056).
CONCLUSIONS
Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.
Topics: Humans; Fatty Acids, Omega-3; Randomized Controlled Trials as Topic; Hemorrhage; Risk Assessment; Risk Factors; Platelet Aggregation Inhibitors
PubMed: 38742535
DOI: 10.1161/JAHA.123.032390 -
JAMA Neurology Jun 2024Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients.
OBJECTIVE
To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection.
DATA SOURCES
PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023.
STUDY SELECTION
Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up.
DATA EXTRACTION/SYNTHESIS
Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses.
RESULTS
Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0).
CONCLUSIONS AND RELEVANCE
This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.
Topics: Humans; Vertebral Artery Dissection; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Anticoagulants; Randomized Controlled Trials as Topic; Stroke; Carotid Artery, Internal, Dissection
PubMed: 38739383
DOI: 10.1001/jamaneurol.2024.1141 -
Cerebrovascular Diseases Extra 2024Moyamoya disease (MMD) is an uncommon cause of stroke. Antiplatelet treatment is commonly prescribed for patients with MMD despite the lack of strong evidence supporting...
INTRODUCTION
Moyamoya disease (MMD) is an uncommon cause of stroke. Antiplatelet treatment is commonly prescribed for patients with MMD despite the lack of strong evidence supporting its efficacy. We conducted a systematic review to evaluate evidence of antiplatelet treatment and clinical outcomes among patients with MMD.
METHODS
A systematic literature search was performed to identify studies that evaluated the association between antiplatelet treatment and clinical outcomes, including ischemic stroke, hemorrhagic stroke, functional outcome, survival, and bypass patency, in patients with MMD. The following databases were searched: PubMed, Embase, Scopus, and the Cochrane Library, from the inception date to February 2022.
RESULTS
Eight studies were included in this systematic review. Six studies evaluated antiplatelet treatment and ischemic stroke. Most studies did not demonstrate a protective effect of antiplatelet treatment against ischemic stroke. Five studies evaluated antiplatelet treatment and hemorrhagic stroke. All of them did not demonstrate an increased risk of hemorrhagic stroke. One study found the benefit of antiplatelet treatment in terms of survival. Regarding the effect of antiplatelet treatment on functional outcome and patency of surgical bypass, the results were inconclusive.
CONCLUSION
Current evidence suggests that antiplatelet treatment in patients with MMD did not demonstrate a protective effect against ischemic stroke. However, antiplatelet treatment did not increase the risk of hemorrhagic stroke in patients with MMD. The well-designed randomized controlled trial should be highlighted.
Topics: Humans; Moyamoya Disease; Platelet Aggregation Inhibitors; Treatment Outcome; Risk Factors; Hemorrhagic Stroke; Ischemic Stroke; Female; Risk Assessment; Male; Middle Aged; Adult; Young Adult; Adolescent; Aged; Child; Child, Preschool
PubMed: 38697036
DOI: 10.1159/000539025 -
American Journal of Cardiovascular... May 2024The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we... (Meta-Analysis)
Meta-Analysis
AIM
The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI.
METHODS
Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs).
RESULTS
When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003).
CONCLUSION
Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.
Topics: Humans; Hirudins; ST Elevation Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Platelet Glycoprotein GPIIb-IIIa Complex; Heparin; Antithrombins; Hemorrhage; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 38683263
DOI: 10.1007/s40256-024-00636-6 -
Journal of the American Heart... May 2024Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta-analysis has focused on minor ischemic stroke alone.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta-analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90-day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5.
METHODS AND RESULTS
Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90-day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random-effects meta-analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90-day stroke recurrence was 8.6% (95% CI, 6.5-10.7), reducing by 0.60% (95% CI, 0.09-1.1; =0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5-8.0) when compared with non-dual antiplatelet trial arms (7.2%, 95% CI, 4.7-9.6) and observational studies 10.6% (95% CI, 7.0-14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference - score ≤3: 8.6% (95% CI, 6.0-11.1), score ≤4: 8.4% (95% CI, 6.1-10.6), as did excluding studies with n<500%-7.3% (95% CI, 5.5-9.0).
CONCLUSIONS
The risk of recurrence after minor ischemic stroke is declining over time but remains important.
Topics: Humans; Recurrence; Observational Studies as Topic; Time Factors; Ischemic Stroke; Risk Factors; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Platelet Aggregation Inhibitors; Severity of Illness Index
PubMed: 38641856
DOI: 10.1161/JAHA.123.032471