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Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049 -
PloS One 2024Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis
Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy of aspirin in preventing colorectal adenoma recurrence in a population with a history of colorectal adenoma but not colorectal cancer, however, the relationship between aspirin dose and colorectal adenoma recurrence remains unclear. We conducted pairwise meta-analysis, meta-regression, trial sequential analysis, and network meta-analysis of all eligible studies. The ROB 2.0 tool was used to assess the risk of bias in the studies. The confidence in network meta-analysis (CINeMA) approach was used to evaluate the confidence of the network meta-analysis results. The network meta-analysis included eight RCTs (nine reports), comprising four on aspirin (low or high dose) alone and four on aspirin combined with another medication, all compared with placebo. In the network meta-analysis, low-dose aspirin (LDA <300 mg per day) was more effective than high-dose aspirin (HDA ≥300 mg per day) and placebo, with risk ratios of 0.76 (95% CI: 0.58 to 0.99) and 0.7 (95% CI: 0.54 to 0.91), respectively. LDA was the optimal treatment relative to HDA and placebo (P-score = 0.99). In the trial sequential analysis, LDA was only more effective than placebo when the number of included participants exceeded the optimal information size; this was not the case for HDA. LDA has statistically significant efficacy for colorectal adenoma prevention, but compared with HDA, its efficacy remains uncertain. Further trials are therefore required.
Topics: Humans; Aspirin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Colorectal Neoplasms; Adenoma
PubMed: 38483854
DOI: 10.1371/journal.pone.0279784 -
Effect of aspirin on blood pressure in hypertensive patients: a systematic review and meta-analysis.BMC Cardiovascular Disorders Feb 2024Aspirin is widely used for secondary prevention in patients with hypertension. However, previous studies mainly focused on the preventive effects of aspirin, and there... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Aspirin is widely used for secondary prevention in patients with hypertension. However, previous studies mainly focused on the preventive effects of aspirin, and there has been a lack of reliable evidence on whether taking aspirin affects blood pressure This study aimed to investigate whether aspirin would affect the blood pressure in patients with hypertension.
METHODS
PubMed, Cochrane database, Embase, Scopus and Medline databases were searched until September 2023. For continuous variables (e.g., blood pressure reduction), the mean difference (MD) was selected as the effect magnitude indices. We used the Cochrane Collaboration's Risk of Bias tool to assess the risk of bias.
RESULT
A total of five studies were included, comprising 20,312 patients. We found that aspirin did not affect SBP (MD = -0.78, 95% CI: - 2.41, 0.84). A similar result was found for DBP (MD = -0.86, 95% CI: - 2.14, 0.42).
CONCLUSION
This study showed no significant difference in blood pressure between the aspirin and control groups, suggesting that aspirin does not affect blood pressure.
Topics: Humans; Blood Pressure; Hypertension; Hypotension; Aspirin
PubMed: 38321368
DOI: 10.1186/s12872-024-03737-x -
PeerJ 2024This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse... (Meta-Analysis)
Meta-Analysis
The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.
BACKGROUND
This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA).
METHOD
The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022.
RESULTS
A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral intravenous routes), 78 in the paracetamol group (oral intravenous routes), and 72 in the ibuprofen group (rectal oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; < 0.0001, = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; = 0.71, = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy.
CONCLUSION
This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Indomethacin; Cyclooxygenase Inhibitors; Infant, Low Birth Weight; Acetaminophen; Infant, Premature
PubMed: 38304184
DOI: 10.7717/peerj.16591 -
American Journal of Cardiovascular... Mar 2024Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin... (Meta-Analysis)
Meta-Analysis
AIM
Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin administered for primary prevention of CVD in patients with chronic kidney disease.
METHODS
PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 22 June 2023. Randomized controlled trials (RCTs) and cohort studies evaluating aspirin as primary prevention of CVD in chronic kidney disease were included. Meta-analysis was conducted using random-effects models.
RESULTS
Overall, 11 studies (6 RCTs and 5 cohort studies) with 24,352 patients were included. The meta-analysis of RCTs indicated that aspirin was associated with lower risk of major adverse cardiovascular events [hazard ratio (HR): 0.79; 95% confidence intervals (CI): 0.64-0.97] and higher risk of major bleeding [risk ratio (RR): 1.35; 95% CI 1.15-1.58]. Incorporating observational evidence led to statistically non-significant findings in terms of risk of both cardiovascular events (pooled HR: 0.97; 95% CI 0.75-1.25; low certainty) and major bleeding (pooled RR: 1.21; 95% CI 0.99-1.48; moderate certainty). No statistically significant differences between aspirin and placebo were observed in the outcomes of mortality, coronary heart disease, stroke and renal events.
CONCLUSIONS
RCT evidence points to a possible benefit in cardiovascular event reduction from aspirin administration, at the cost of increased major bleeding risk. This finding was not confirmed when the existing observational evidence was incorporated. Further research should determine the most appropriate subpopulation of chronic kidney disease patients that would benefit the most from prophylactic aspirin therapy.
REGISTRATION
The study protocol has been prospectively registered and is publicly available from: https://doi.org/10.17504/protocols.io.261ged63jv47/v1 .
Topics: Humans; Cardiovascular Diseases; Aspirin; Hemorrhage; Renal Insufficiency, Chronic; Primary Prevention
PubMed: 38296933
DOI: 10.1007/s40256-024-00630-y -
Orphanet Journal of Rare Diseases Jan 2024The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring.
METHODS
PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I statistic for heterogeneity and publication bias was calculated.
RESULTS
Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I = 39.4%).
CONCLUSIONS
These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
Topics: Female; Humans; Pregnancy; Aspirin; Contraceptives, Oral; Gastroschisis; Ibuprofen; Phenylpropanolamine; Pseudoephedrine; Observational Studies as Topic
PubMed: 38287353
DOI: 10.1186/s13023-023-02992-z -
BMC Pregnancy and Childbirth Jan 2024To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia.
SEARCH STRATEGY
PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords "preeclampsia", "Low Molecular Weight Heparin", "LMWH", "Heparin, Low Molecular Weight", "Dalteparin", "Nadroparin", and "Tinzaparin".
SELECTION CRITERIA
Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia.
DATA COLLECTION AND ANALYSIS
Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption.
CONCLUSION
For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.
Topics: Female; Infant, Newborn; Humans; Pregnancy; Heparin, Low-Molecular-Weight; Pre-Eclampsia; Pregnancy, High-Risk; Premature Birth; Fetal Growth Retardation; Aspirin; Heparin; Nadroparin; Thrombophilia; Anticoagulants
PubMed: 38233773
DOI: 10.1186/s12884-023-06218-9 -
Journal of Orthopaedics and... Jan 2024Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA). A Bayesian network meta-analysis was performed, setting as outcomes of interest the rate of deep venous thrombosis (DVT), pulmonary embolism (PE) and major and minor haemorrhages.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. All randomised controlled trials (RCTs) comparing two or more drugs used for the prophylaxis of VTE following THA were accessed. PubMed, Web of Science and Google Scholar databases were accessed in March 2023 with no time constraint.
RESULTS
Data from 31,705 patients were extracted. Of these, 62% (19,824) were women, with age, sex ratio, and body mass index (BMI) being comparable at baseline. Apixaban 5 mg, fondaparinux, and rivaroxaban 60 mg were the most effective in reducing the rate of DVT. Dabigatran 220 mg, apixaban 5 mg, and aspirin 100 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, ximelagatran 2 mg and aspirin 100 mg were associated with the lowest rate of major haemorrhages, while rivaroxaban 2.5 mg, apixaban 5 mg and enoxaparin 40 mg were associated with the lowest rate of minor haemorrhages.
CONCLUSION
Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following THA. Level of evidence Level I, network meta-analysis of RCTs.
Topics: Female; Humans; Male; Arthroplasty, Replacement, Hip; Aspirin; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism
PubMed: 38194191
DOI: 10.1186/s10195-023-00742-2 -
The Western Journal of Emergency... Nov 2023Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food...
INTRODUCTION
Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.
METHODS
We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.
RESULTS
Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.
CONCLUSION
For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.
Topics: Child; Humans; Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Infusions, Intravenous
PubMed: 38165196
DOI: 10.5811/westjem.59099 -
Scientific Reports Dec 2023Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache... (Meta-Analysis)
Meta-Analysis
Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache Disorders. TTH is treated with over-the-counter medications, mostly paracetamol or ibuprofen. The purpose was to assess the effectiveness of paracetamol versus ibuprofen in treating episodic tension-type headache (ETTH) through direct and indirect comparisons of randomized controlled trials (RCTs). We included RCTs comparing paracetamol with a placebo, ibuprofen with a placebo, or paracetamol with ibuprofen for acute ETTH treatment that were published between 1988 and 2022. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Web of Science. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias. We identified 14 studies including 6521 people with ETTH. None of the studies had a low risk of bias for all domains; this was most likely due to inadequate reporting and a small sample size. Ibuprofen (odds ratio (OR): 1.73, 95% confidence interval (CI): 1.17-2.56) showed better efficacy than paracetamol (OR: 1.62, 95% CI 1.24-2.13) for pain-free status at 2 h, while paracetamol (OR: 1.42, 95% CI 0.87-2.30) showed better efficacy than ibuprofen (OR: 1.20, 95% CI 0.58-2.48) for pain-free status at 1 h. Paracetamol was associated with the lowest likelihood of rescue medication use (OR: 0.49, 95% CI 0.37-0.65). Ibuprofen was associated with a lower likelihood of the occurrence of any events and gastrointestinal adverse events compared with placebo and paracetamol (OR: 0.95, 95% CI 0.64-1.41 and OR: 0.81, 95% CI 0.44-1.50, respectively). Paracetamol and ibuprofen showed better efficacy than placebo in treating ETTH; there was no statistically significant difference in efficacy between the two drugs. For individuals at a higher risk (like renal insufficiency or risk of GI bleeding), paracetamol may be considered as a preferred option instead of Ibuprofen. Further meta-analyses of head-to-head trials are needed for direct comparisons in the future.PROSPERO registration number: CRD42022340936.
Topics: Humans; Acetaminophen; Ibuprofen; Analgesics, Non-Narcotic; Tension-Type Headache; Network Meta-Analysis
PubMed: 38057585
DOI: 10.1038/s41598-023-48910-y