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Stroke Feb 2018Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders.
RESULTS
We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16; <0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01-1.29; =0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; =0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04-1.61; =0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03-1.47; =0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93-1.52; =0.16).
CONCLUSIONS
Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.
Topics: Brain Ischemia; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Stroke; Thienopyridines
PubMed: 29339434
DOI: 10.1161/STROKEAHA.117.019166 -
Ontario Health Technology Assessment... 2017Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in people with atrial fibrillation include pharmacological agents such as novel oral anticoagulants or nonpharmacological devices such as the left atrial appendage closure device with delivery system (LAAC device). The objectives of this health technology assessment were to assess the clinical effectiveness and cost-effectiveness of the LAAC device versus novel oral anticoagulants in patients without contraindications to oral anticoagulants and versus antiplatelet agents in patients with contraindications to oral anticoagulants.
METHODS
We performed a systematic review and network meta-analysis. We also conducted an economic literature review, economic evaluation, and budget impact analysis to assess the cost-effectiveness and budget impact of the LAAC device compared with novel oral anticoagulants and oral antiplatelet agents (e.g., aspirin). We also spoke with patients to better understand their preferences, perspectives, and values.
RESULTS
Seven randomized controlled studies met the inclusion criteria for indirect comparison. Five studies assessed the effectiveness of novel oral anticoagulants versus warfarin, and two studies compared the LAAC device with warfarin. No studies were identified that compared the LAAC device with aspirin in patients in whom oral anticoagulants were contraindicated. Using the random effects model, we found that the LAAC device was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR] 0.85; credible interval [Cr.I] 0.63-1.05). Similarly, the reduction in the risk of all-cause mortality was comparable between the LAAC device and novel oral anticoagulants (OR 0.71; Cr.I 0.49-1.22). The LAAC device was found to be superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45; Cr.I 0.29-0.79), whereas novel oral anticoagulants were found to be superior to the LAAC device in preventing ischemic stroke (OR 0.67; Cr.I 0.24-1.64). The body of clinical evidence was found to be of moderate quality as assed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results from the economic evaluation indicate that the LAAC device is cost-effective compared with aspirin in patients with contraindications to oral anticoagulants. In patients without contraindications to oral anticoagulants, we found that the LAAC device is not cost-effective compared with novel oral anticoagulants. Publicly funding the LAAC device in patients with nonvalvular atrial fibrillation with contraindications to oral anticoagulants could result in additional funding of $1.1 million to $7.7 million over the first five years. Patients interviewed reported on the impact of living with nonvalvular atrial fibrillation and were supportive of the LAAC device as a treatment option.
CONCLUSIONS
Moderate-quality evidence suggests that the LAAC device is as effective as novel oral anticoagulants in preventing stroke in people with nonvalvular atrial fibrillation. However, our results indicate that the LAAC device is cost-effective only in patients with contraindications to oral anticoagulants. People with nonvalvular atrial fibrillation with whom we spoke reported positive support for the LAAC device.
Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Platelet Aggregation Inhibitors; Stroke
PubMed: 28744335
DOI: No ID Found -
The Cochrane Database of Systematic... Feb 2018Prostaglandin E1 (PGE1) is used to keep the ductus arteriosus patent and can be life-saving in neonates with ductal-dependent cardiac lesions. PGE1 is used to promote... (Review)
Review
BACKGROUND
Prostaglandin E1 (PGE1) is used to keep the ductus arteriosus patent and can be life-saving in neonates with ductal-dependent cardiac lesions. PGE1 is used to promote mixing of pulmonary and systemic blood flow or improve pulmonary or systemic circulations, prior to balloon atrial septostomy or surgery. PGE1 therapy may cause several short-term and long-term adverse effects. The efficacy and safety of PGE1 in neonates with ductal-dependent cardiac lesions has not been systematically reviewed.
OBJECTIVES
To determine the efficacy and safety of both short-term (< 120 hours) and long-term (≥120 hours) PGE1 therapy in maintaining patency of the ductus arteriosus and decreasing mortality in ductal-dependent cardiac lesions.
SEARCH METHODS
We searched the literature in October 2017, using the search strategy recommended by Cochrane Neonatal. We searched electronic databases (CENTRAL (in the Cochrane Library), MEDLINE, CINAHL, Embase); abstracts of the Pediatric Academic Societies; websites for registered trials at www.clinicaltrials.gov and www.controlled-trials.com; and in the reference list of identified articles.
SELECTION CRITERIA
Randomized or quasi-randomized trials using PGE1 at any dose or duration to maintain ductal patency in term or late preterm (≥ 34 weeks' gestation) infants with ductal-dependent cardiac lesions and which reported effectiveness and safety in the short term or long term.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methods for conducting a systematic review. Two review authors (SA and MP) independently assessed the titles and abstracts of studies identified by the search strategy to determine eligibility for inclusion. We obtained the full-text version if eligibility could not be done reliably by title and abstract. We resolved any differences by discussion. We designed electronic forms for trial inclusion/exclusion, data extraction, and for requesting additional published information from authors of the original reports.
MAIN RESULTS
Our search did not identify any completed or ongoing trials that met our inclusion criteria.
AUTHORS' CONCLUSIONS
There is insufficient evidence from randomized controlled trials to determine the safety and efficacy of PGE1 in neonates with ductal-dependent cardiac lesions. Evidence from observational trials have informed clinical practice on the use of PGE, which is now considered the standard of care for ductal-dependent cardiac lesions. It is unlikely that randomized controlled studies will be performed for this indication but comparative efficacy of newer formulations of PGE1, different doses of PGE1 and studies comparing PGE with PDA stents or other measures to keep the ductus open may be ethical and necessary.
Topics: Alprostadil; Ductus Arteriosus, Patent; Humans; Infant, Newborn; Vasodilator Agents
PubMed: 29486048
DOI: 10.1002/14651858.CD011417.pub2 -
European Journal of Medical Research Jul 2023Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.
METHODS
A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.
RESULTS
A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63-0.76, I = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80-0.82, I = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61-0.73, I = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99-1.31, I = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.
CONCLUSION
Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.
Topics: Humans; Carcinoma, Hepatocellular; Aspirin; Liver Neoplasms; Prospective Studies; Retrospective Studies; Gastrointestinal Hemorrhage
PubMed: 37422691
DOI: 10.1186/s40001-023-01204-5 -
The Korean Journal of Internal Medicine Jan 2024There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB.
METHODS
A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review.
RESULTS
We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc.
CONCLUSION
The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.
Topics: Humans; Anemia; Anticoagulants; Diltiazem; Gastrointestinal Hemorrhage; Gemfibrozil; Heart Failure; Helicobacter Infections; Helicobacter pylori; Myocardial Infarction; Risk Factors; Verapamil
PubMed: 38062723
DOI: 10.3904/kjim.2023.098 -
Clinical Neurology and Neurosurgery Sep 2023About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by stimulating platelet aggregation. Tirofiban is a selective and rapidly activated antagonist of the platelets nonpeptide glycoprotein IIb/IIIa receptors that can reversibly suppress platelet aggregation. But, data from the medical literature are conflicting regarding its safety and efficacy for stroke patients. Hence, this study was designed to assess the safety and efficacy of tirofiban in stroke patients.
METHODS
Five major databases (PubMed, Scopus, Web of Science, Embase, and Cochrane library) were searched till December 2022. The Cochrane tool was used for risk of bias assessment, and the RevMan 5.4 was utilized for data analysis.
RESULTS
Seven RCTs with 2088 stroke patients were included. Tirofiban significantly increased the number of patients with mRS 0 score after 90 days than control; RR= 1.39, 95 %CI [1.15, 1.69]; p = 0.0006. Additionally, it reduced the NIHSS score after seven days; MD= -0.60, 95 %CI [-1.14, -0.06]; p = 0.03. However, tirofiban increased the incidence of intracranial haemorrhage (ICH); RR= 1.22, 95 %CI [1.03, 1.44]; p = 0.02. Other assessed outcomes showed insignificant results.
CONCLUSIONS
Tirofiban was associated with a higher mRS 0 score after three months and a lower NIHSS score after seven days. However, it is associated with higher ICH. Multicentric trials are required to provide more convincing proof of its utility.
Topics: Humans; Tirofiban; Platelet Aggregation Inhibitors; Brain Ischemia; Treatment Outcome; Randomized Controlled Trials as Topic; Stroke; Intracranial Hemorrhages
PubMed: 37423089
DOI: 10.1016/j.clineuro.2023.107867 -
Chinese Medical Journal Apr 2023Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.
METHODS
We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.
RESULTS
Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.
CONCLUSIONS
Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.
REGISTRATION
PROSPERO, No. CRD42022296376.
Topics: Humans; Cyclooxygenase 2 Inhibitors; Calcium; Network Meta-Analysis; Vitamins; Colorectal Neoplasms; Chemoprevention; Aspirin; Adenoma; Vitamin D
PubMed: 37027286
DOI: 10.1097/CM9.0000000000002514 -
British Journal of Clinical Pharmacology May 2021This meta-analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy. (Meta-Analysis)
Meta-Analysis Review
AIM
This meta-analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy.
METHODS
PubMed, Web of Science, EMBASE and the Cochrane Library were searched from the inception of each database to 5 May 2020. Studies reporting endpoints in genotype-guided treatment group and conventional treatment group were included. The endpoint results were presented as the risk ratio (RR), with 95% confidence interval (CI).
RESULTS
A total of 10 561 patients from 16 studies (eight randomized controlled trials [RCT] and eight cohort studies) were included in the meta-analysis. The rates of major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction (MI) were significantly lower in the genotype-guided group than in the conventional treatment group (RR 0.56, 95% CI 0.44-0.73, P < .0001; RR 0.40, 95% CI 0.24-0.67, P = .0005; RR 0.45, 95% CI 0.35-0.58, P < .00001, respectively). A significant difference was found between the two groups in major bleeding (RR 0.73, 95% CI 0.55-0.98, P = .04), which was not robust after sensitivity analysis.
CONCLUSION
Genotype-guided antiplatelet treatment could decrease the risk of MACE, stent thrombosis and MI in patients with coronary artery disease or undergoing percutaneous coronary intervention, without increasing the risk of bleeding over a long follow-up period. The decreased risk of efficacy outcomes was more obvious in cohort studies. Well-organized RCTs and clinical trials are required to verify the benefit of genotype-guided therapy.
Topics: Acute Coronary Syndrome; Genotype; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 33140858
DOI: 10.1111/bcp.14637 -
Stroke and Vascular Neurology Sep 2021Stroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention.
METHODS
MEDLINE, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020, for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo, in patients with ischaemic stroke. Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess study quality. This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
Eighteen randomised trials comprising 11 429 participants were included in this meta-analysis. Most trials possessed low risk of bias and were of low heterogeneity. Cilostazol significantly reduced the rate of ischaemic stroke recurrence (risk ratio, RR=0.69, 95% CI 0.58 to 0.81), any stroke recurrence (RR=0.64, 95% CI 0.54 to 0.74) and major adverse cardiovascular events (RR=0.67, 95% CI 0.56 to 0.81). Cilostazol did not significantly decrease mortality (RR=0.90, 95% CI 0.64 to 1.25) or increase the rate of good functional outcome (Modified Rankin Scale score of 0-1; RR=1.07, 95% CI 0.95 to 1.19). Cilostazol demonstrated favourable safety profile, significantly reducing the risk of intracranial haemorrhage (RR=0.46, 95% CI 0.31 to 0.68) and major haemorrhagic events (RR=0.49, 95% CI 0.34 to 0.70).
CONCLUSIONS
Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes. Future randomised trials can be conducted outside East Asia, or compare cilostazol with a wider range of antiplatelet agents.
Topics: Brain Ischemia; Cilostazol; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke
PubMed: 33542092
DOI: 10.1136/svn-2020-000737 -
Systematic Reviews Aug 2023Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition.
METHODS
We searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies.
RESULTS
We included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP.
CONCLUSIONS
Our study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.
Topics: Humans; Pentoxifylline; Tocopherols; Diarrhea; Proctitis
PubMed: 37608385
DOI: 10.1186/s13643-023-02294-2