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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 -
BMC Cardiovascular Disorders Mar 2024Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period.
METHODS
The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA).
RESULTS
A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine.
CONCLUSION
Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.
Topics: Humans; Anesthetics; Bradycardia; Dexmedetomidine; Emergence Delirium; Hypnotics and Sedatives; Midazolam; Propofol; Saline Solution; Sevoflurane; Network Meta-Analysis
PubMed: 38448835
DOI: 10.1186/s12872-024-03783-5 -
The American Journal of Cardiology Apr 2024Clinical practice guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent left ventricular thrombus (LVT)... (Meta-Analysis)
Meta-Analysis
Clinical practice guidelines from the American Heart Association recommend consideration of prophylactic anticoagulation to prevent left ventricular thrombus (LVT) formation in patients with anterior ST-elevation myocardial infarction. These guidelines were given a low certainty of evidence (class IIb, level C), relying primarily on case studies and expert consensus to inform practice. Our objective was to compare the safety and efficacy of prophylactic anticoagulation, in addition to dual antiplatelet therapy, in the current era of timely primary percutaneous coronary intervention. Electronic databases, including EMBASE, MEDLINE, and Cochrane Library, were systematically searched from January 2012 through June 2022. A total of 7,378 publications were screened, and 5 publications were eventually included in this review: 1 randomized control trial and 4 retrospective studies involving 1,461 patients. Data were pooled using a fixed-effects model and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome of interest was the rate of LVT formation, and the secondary outcomes were the rate of major bleeding and systemic embolism. Pooled analysis showed a significantly lower rate of LVT formation (OR 0.28, 95% CI 0.11 to 0.73, p <0.01) and significantly higher rates of bleeding (OR 2.85, 95% CI 1.13 to 7.24, p = 0.03) in the triple therapy group compared with dual antiplatelet therapy. No significant difference was observed in the rate of systemic embolism between the groups (OR 0.37, 95% CI 0.12 to 1.13, p = 0.08). In this meta-analysis, there is no conclusive evidence to either support or oppose the use of triple therapy for LVT prevention in patients with anterior ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Appropriately powered randomized controlled trials are warranted to further evaluate the benefits of LVT prevention against the risks of major bleeding in this population.
Topics: Humans; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Retrospective Studies; Myocardial Infarction; Thrombosis; Hemorrhage; Embolism; Anticoagulants; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic
PubMed: 38412882
DOI: 10.1016/j.amjcard.2024.02.023 -
PloS One 2024The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is... (Meta-Analysis)
Meta-Analysis
Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression.
BACKGROUND
The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is presently uncertain. However, it is important to highlight the potential benefits of combining this medication with known thrombolytics or antiplatelet therapy. One notable advantage of argatroban is its short half-life, which helps minimize excessive anticoagulation and risk of bleeding complications in inadvertent cases of hemorrhagic stroke. By conducting a meticulous review and meta-analysis, we aim to further explore the common use of argatroban and examine the plausible advantages of combining this medication with established thrombolytic and antiplatelet therapies.
METHOD
In this study, we performed a rigorous and methodical search for both randomized controlled trials and retrospective analyses. Our main objective was to analyze the impact of argatroban on the occurrence of hemorrhagic events and the mRS scores of 0-2. We utilized a meta-analysis to assess the relative risk (RR) associated with using argatroban versus not using it.
RESULTS
In this study, we analyzed data from 11 different studies, encompassing a total of 8,635 patients. Out of these patients, 3999(46.3%) received argatroban treatment while the remaining 4636(53.7%)did not. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) showed that the risk ratio (RR) for patients using argatroban after alteplase thrombolytic therapy compared to those not using argatroban was(RR, 1.00 ([95% CI, 0.92-1.09]; P = 0.97), indicating no statistical significance. However, for patients using argatroban after antiplatelet therapy, was (RR,1.09 [95% CI, 1.04-1.14]; P = 0.0001), which was statistically significant. In terms of hemorrhagic events, the RR for patients using argatroban compared to those not using argatroban was (RR,1.08 [95% CI, 0.88-1.33]; P = 0.46), indicating no statistical significance.
CONCLUSION
The results of this study suggest that further research into combination therapy with argatroban and antiplatelet agents may be warranted, however more rigorous RCTs are needed to definitively evaluate the effects of combination treatment.
Topics: Humans; Platelet Aggregation Inhibitors; Tissue Plasminogen Activator; Retrospective Studies; Stroke; Hemorrhage; Fibrinolytic Agents; Thrombolytic Therapy; Treatment Outcome; Randomized Controlled Trials as Topic; Arginine; Pipecolic Acids; Sulfonamides
PubMed: 38412157
DOI: 10.1371/journal.pone.0298226 -
European Stroke Journal Mar 2024A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor...
A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.
Topics: Humans; Brain Ischemia; Cerebral Small Vessel Diseases; Lipids; Platelet Aggregation Inhibitors; Stroke; Stroke, Lacunar
PubMed: 38380638
DOI: 10.1177/23969873231219416 -
Journal of Orthopaedic Surgery and... Feb 2024There is still a lack of sufficient evidence-based medical data on the effect of resveratrol (Res) on primary osteoporosis (OP). This meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still a lack of sufficient evidence-based medical data on the effect of resveratrol (Res) on primary osteoporosis (OP). This meta-analysis aimed to comprehensively evaluate the role of Res in animal models of primary OP.
METHODS
The PubMed, Cochrane Library, Web of Science and Embase databases were searched up to August 2023. The risk of bias was assessed by the SYRCLE RoB tool. Random- or fixed-effects models were used to determine the 90% confidence interval (CI) or standardized mean difference (SMD). Statistical analysis was performed with RevMan 5.4 and Stata 14.0.
RESULTS
A total of 24 studies containing 714 individuals were included. Compared with those in the control group, the bone mineral density (BMD) (P < 0.00001), bone volume/total volume (BV/TV) (P < 0.001), trabecular thickness (Tb.Th) (P < 0.00001), and trabecular number (Tb.N) (P < 0.00001) were markedly greater, and the trabecular separation (Tb.Sp) (P < 0.00001) was significantly greater. Compared with the control group, the Res group also exhibited marked decreases in alkaline phosphatase (ALP) (P < 0.05), tartrate-resistant acid phosphatase 5b (TRAP5b) (P < 0.01), and type I collagen strong carboxyl peptide (CTX-1) (P < 0.00001) and a marked increase in osteoprotegerin (OPG) (P < 0.00001).
CONCLUSION
In summary, we concluded that Res can markedly increase BMD, improve morphometric indices of trabecular microstructure and serum bone turnover markers (BTMs), and exert a protective effect in animal models of primary osteoporosis. This study can supply experimental reference for Res in primary osteoporosis treatment.
Topics: Animals; Humans; Osteoporosis; Resveratrol; Bone Density; Alkaline Phosphatase; Models, Animal
PubMed: 38350991
DOI: 10.1186/s13018-024-04595-1 -
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 -
PloS One 2024Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.
METHODS
Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.
RESULTS
Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.
CONCLUSION
According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.
Topics: Humans; Platelet Aggregation Inhibitors; COVID-19; Hemorrhage; Thrombosis
PubMed: 38300975
DOI: 10.1371/journal.pone.0297628 -
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