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Journal of the American Heart... Feb 2024There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies.
METHODS AND RESULTS
We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, =0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (=0.14 and =0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30).
CONCLUSIONS
We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies.
REGISTRATION
URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.
Topics: Humans; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Cholesterol, LDL; Hemorrhagic Stroke; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Ezetimibe; Stroke; Triglycerides
PubMed: 38323514
DOI: 10.1161/JAHA.123.030714 -
Semergen 2024Monacolin K is the major active component in red yeast rice (RYR) which is structurally identical to lovastatin and has the most powerful effect, in terms of reducing... (Review)
Review
Monacolin K is the major active component in red yeast rice (RYR) which is structurally identical to lovastatin and has the most powerful effect, in terms of reducing blood cholesterol levels. This review aimed to examine the effect and safety of different doses of monacolin K on blood cholesterol levels. PubMed and Cochrane were searched for articles published between 2012 and 2023 for clinical-trials and randomized-controlled-trials. Eligible studies included participants>18-years-old, of any gender and ethnicity. The intervention/exposure of interest was monacolin K. Hypercholesterolemia was considered the outcome of interest defined as the elevated total or low-density-lipoprotein (LDL) cholesterol levels. 12 randomized-controlled-trials were eligible for inclusion in the analysis including 769 participants>18-years-old. 11 out of 12 studies were assessed with high methodological quality and one study with low methodological quality. Monacolin K supplementation varied between 2mg and 10mg per day and the maximum period of supplementation was 12 weeks. All studies indicated a beneficial effect of monacolin supplementation on LDL and total cholesterol levels (p<0.05) regardless the dose and period of supplementation. Also, 3 of the included studies reported adverse side effects after treatment with monacolin K. Low doses of monacolin K equal to 3mg/day exert potential cholesterol-lowering effects although the number of relative studies is limited. Regarding the safety of monacolin K supplementation, findings seem to be more controversial and therefore, it is suggested for all patients treated with monacolin K to be routinely monitored regardless the dose of supplementation.
Topics: Humans; Hypercholesterolemia; Dietary Supplements; Randomized Controlled Trials as Topic; Lovastatin; Anticholesteremic Agents; Cholesterol, LDL; Dose-Response Relationship, Drug; Cholesterol; Biological Products; Dicarboxylic Acids; Fatty Acids
PubMed: 38310834
DOI: 10.1016/j.semerg.2023.102156 -
Clinical Breast Cancer Apr 2024Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the... (Meta-Analysis)
Meta-Analysis Review
Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC. Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to June 2022. Studies were included if they compared patients with TNBC receiving and not receiving statin therapy concurrently with oncologic treatment for curative intent in terms of recurrence and survival in a non-metastatic setting. The primary outcomes were 5-year disease-free survival (DFS) and 5-year overall survival (OS). A pairwise meta-analyses was performed using inverse variance random effects. Risk of bias was assessed with the ROBINS-I and the GRADE approach was conducted to assess quality of evidence. From 4014 citations, 5 studies with 625 patients on statin therapy and 2707 patients not on statin therapy were included. There was a significant increase in 5-year DFS for patients on statin therapy compared to patients not on statin therapy (OR 1.44, 95% CI 1.04-1.98, P = .03). No significant difference was noted in 5-year OS between the 2 groups (OR 1.12, 95% CI 0.86-1.47, P = .40). Included studies were at moderate-to-high risk of bias. The GRADE quality of evidence was very low. This review presents very low-quality evidence that concurrent use of statins with oncologic treatment may potentially improve long-term DFS for patients with TNBC undergoing curative intent therapy. Future research by way of large, prospective study is required to further clarify the clinical utility of statins on patients undergoing treatment for TNBC.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Triple Negative Breast Neoplasms; Disease-Free Survival; Tumor Microenvironment
PubMed: 38296737
DOI: 10.1016/j.clbc.2023.12.001 -
Current Pharmaceutical Design 2024Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive.
AIM
We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs).
METHODS
Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence.
RESULTS
A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant.
CONCLUSION
It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Lipids
PubMed: 38288799
DOI: 10.2174/0113816128285148240122112045 -
Hepatology Communications Feb 2024It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for individualized therapy. The existence of potential heterogeneity in the treatment response can be assessed using the variability ratio (VR) of the outcome measurement (in this case, HVPG) between the treated and placebo groups. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the potential heterogeneity in the portal pressure response to NSBBs.
METHODS
After a systematic search, we quantified the heterogeneity of treatment response with the VR between the treatment and control groups, with VR > 1 indicating potential heterogeneity. We used a similar approach to compare carvedilol with propranolol and statins with placebo.
RESULTS
We identified 18 studies that included 965 patients. A comparison between beta-blockers and placebo showed a pooled VR of 0.99 (95% CI:0.87-1.14), which suggests a homogeneous HVPG response to NSBB at the individual patient level (ie, no evidence to support that some patients responded to beta-blockers and others did not). For the comparison between carvedilol and propranolol, pooled VR was 0.97 (95% CI 0.82-1.14), suggesting that carvedilol achieves a greater average response (rather than an increase in the proportion of responders). There was no evidence of a heterogeneous response to statins.
CONCLUSION
Our analysis did not support the existence of a heterogeneous patient-by-patient response to NSBBs in cirrhosis. These findings challenge the concept of personalized therapy based on portal pressure response and indicate that routine portal pressure measurement may not be necessary to guide NSBB therapy.
Topics: Humans; Propranolol; Carvedilol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Adrenergic beta-Antagonists; Hypertension, Portal
PubMed: 38285880
DOI: 10.1097/HC9.0000000000000321 -
PloS One 2024Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness.
METHODS
A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated.
RESULTS
Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27).
CONCLUSIONS
In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.
Topics: Humans; Dicarboxylic Acids; Fatty Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic
PubMed: 38277431
DOI: 10.1371/journal.pone.0297854 -
Journal of Cardiovascular Computed... 2024Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This systematic review aimed to compare changes in aspirin and statin therapy following CCTA and functional stress testing in patients with suspected CAD, and in those underwent CCTA when stratified by the presence/absence of plaque.
RESULTS
Eight studies involving 42,812 CCTA patients and 64,118 cardiac stress testing patients were analyzed. Compared to functional testing, CCTA led to 66 % more changes in statin therapy (pooled RR, 95 % CI [1.28-2.15]) and a 74 % increase in aspirin prescriptions (pooled RR, 95 % CI [1.34-2.26]). For medication modifications based on CCTA results, 13 studies (47,112 patients with statin data) and 11 studies (12,089 patients with aspirin data) were included. Patients with any plaque on CCTA were five times more likely to use or intensify statins compared to those without CAD (pooled RR, 5.40, 95 % CI [4.16-7.00]). Significant heterogeneity remained, which decreased when stratified by diabetes rates. Aspirin use increased eightfold after plaque detection (pooled RR, 8.94 [95 % CI, 4.21-19.01]), especially with obstructive plaque findings (pooled RR, 9.41, 95 % CI [2.80-39.02]).
CONCLUSION
In conclusion, CCTA resulted in higher changes in statin and aspirin therapy compared to cardiac stress testing. Detection of plaque by CCTA significantly increased statin and aspirin therapy.
Topics: Aged; Female; Humans; Male; Middle Aged; Angina Pectoris; Aspirin; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Exercise Test; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 38262852
DOI: 10.1016/j.jcct.2024.01.006 -
American Journal of Cardiovascular... Jan 2024Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors (PCSK9i) have a beneficial effect on various domains of patients' lipid profiles and cardiovascular and mortality outcomes. Here, we aim to further investigate the efficacy and safety of PCSK9i in patients with ACS or who experienced recent episodes.
METHODS
We comprehensively searched PubMed, Scopus, Web of Science and Cochrane CENTRAL to identify all randomized controlled trials comparing PCSK9i versus placebo. Data were extracted and analysed using Stata/MP version 17.0.
RESULTS
Eleven studies (n = 24,732) were included in this meta-analysis. In terms of efficacy outcomes, compared with the control group, PCSK9i significantly decreased levels of LDL-C, TC, TG, Lp (a) and Apo-B, with the following values, respectively: Cohen's d of - 1.25, 95% confidence interval (CI - 1.64 to - 0.87); Cohen's d of - 1.32, 95% CI (- 1.83 to - 0.81); Cohen's d of - 0.26, 95% CI (- 0.37 to - 0.14); Cohen's d of - 0.70, 95% CI (- 1.15 to - 0.26); and Cohen's d of - 1.46, 95% CI (- 1.97 to - 0.94). The levels of HDL-C and Apo-A1 increased by: Cohen's d 0.27, 95% CI (0.16-0.39) and Cohen's d of 0.30, 95% CI (0.17-0.42), respectively. Regarding safety outcomes, PCSK9i was associated with lower odds of myocardial infarction (MI) and cerebrovascular events with the following values, respectively: OR = 0.87, 95% CI (0.78-0.97) and OR = 0.71, 95% CI (0.52-0.98).
CONCLUSIONS
PCSK9i was associated with better lipid profile and quality of life of patients and can be recommended as an optimal treatment strategy. Further trials should study combinations of PCSK9i with other lipid-lowering drugs.
Topics: Humans; Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, LDL; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38241002
DOI: 10.1007/s40256-023-00621-5 -
International Journal of Cardiology Mar 2024To explore the safety and assess the cardiovascular impact of early in-hospital administration of PCSK9 inhibitors in patients with acute coronary syndrome (ACS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the safety and assess the cardiovascular impact of early in-hospital administration of PCSK9 inhibitors in patients with acute coronary syndrome (ACS).
METHODS
A systematic search of PubMed, Web of Science, and Embase databases was conducted for studies involving the use of PCSK9 inhibitors in ACS patients from inception to October 2023. Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using STATA 16.0 software.
RESULTS
Nine studies, encompassing a total of 2896 ACS patients, were included in the analysis. When compared to statin monotherapy, early administration of PCSK9 inhibitors during hospitalization for ACS proved effective in reducing the incidence of major adverse cardiovascular events (MACEs). This encompassed a decrease in coronary revascularization [Relative Risk (RR) = 0.78, 95% CI (0.62, 0.98), P < 0.05], recurrent ACS [RR = 0.62, 95% CI (0.42, 0.94), P < 0.05], readmissions due to unstable angina [RR = 0.71, 95% CI (0.59, 0.85), P < 0.01], and strokes [RR = 0.31, 95% CI (0.09, 1.04), P = 0.058]. There was no significant difference in the incidence of death between the two groups.The use of PCSK9 inhibitors notably hastened the reduction of LDL-C, TG, and Non HDL-C levels in the short term. Additionally, it increased HDL-C levels and the number of individuals meeting LDL-C compliance criteria. Importantly, the risk of adverse drug events, such as ALT increase >3xULN, allergies, and musculoskeletal pain, did not significantly elevate with PCSK9 inhibitor use.
CONCLUSION
The early administration of PCSK9 inhibitors has been found to safely and effectively lower diverse lipid levels in patients with ACS. This reduction is associated with a noteworthy decrease in MACEs, encompassing revascularization, recurrent ACS, and hospital readmissions.
Topics: Humans; Acute Coronary Syndrome; PCSK9 Inhibitors; Proprotein Convertase 9; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hospitals; Anticholesteremic Agents
PubMed: 38211676
DOI: 10.1016/j.ijcard.2024.131775 -
BMC Oral Health Jan 2024Hemorrhage control is a crucial aspect of dental procedures, and achieving efficient hemostasis remains a key challenge. The advent of hemostatic dressings has... (Meta-Analysis)
Meta-Analysis
Hemorrhage control is a crucial aspect of dental procedures, and achieving efficient hemostasis remains a key challenge. The advent of hemostatic dressings has revolutionized the field of dentistry by providing effective and convenient solutions for managing bleeding in vari-ous dental scenarios. This article aims to provide an overview of hemostatic dressings, their mechanisms of action, and their diverse applications in dentistry. We applied the following Pop-ulation, Exposure, Comparator, and Outcomes (PICO) model to assess the document eligibility. A literature search was performed on major search engines, using keywords. At the end of the search, 3 articles were selected that matched the PICO. Three items were selected after the screen-ing process, and bleeding times were analyzed between the control group and the study group. The overall effect showed a substantial and statistically significant difference with bleeding time in favour of HDD-treated patients, showing that this garrison is very useful in controlling bleed-ing for patients taking anticoagulants and antiplatelets (Mean difference - 5.61; C.I. -5.70, - 5.52); Overall, hemostatic dressings have revolutionized the management of bleeding in dentistry, offering a promising solution to achieve optimal hemostasis, improve treatment outcomes, and enhance patient care, particularly Hemcon.
Topics: Humans; Hemostatics; Chitosan; Anticoagulants; Hemostasis; Dentistry
PubMed: 38200485
DOI: 10.1186/s12903-023-03568-w