-
PloS One 2024Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk.
METHODS
We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs.
RESULTS
We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47).
CONCLUSION
LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations.
PROSPERO REGISTRATION
CRD42021271658.
Topics: Humans; Aged; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Neoplasms; Lipids
PubMed: 38329982
DOI: 10.1371/journal.pone.0297852 -
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 -
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 -
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 -
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 -
Complementary Therapies in Medicine Mar 2024Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST).
METHODS
The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes.
RESULTS
Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction.
CONCLUSION
Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.
Topics: Adult; Humans; Liver; Dietary Supplements; Randomized Controlled Trials as Topic; Fatty Alcohols; Alanine Transaminase; Aspartate Aminotransferases
PubMed: 38185399
DOI: 10.1016/j.ctim.2024.103018 -
PloS One 2024Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to... (Meta-Analysis)
Meta-Analysis
Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.
Topics: Humans; Atorvastatin; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Treatment Outcome
PubMed: 38165842
DOI: 10.1371/journal.pone.0293404 -
Yonsei Medical Journal Jan 2024There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe... (Meta-Analysis)
Meta-Analysis
PURPOSE
There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin.
MATERIALS AND METHODS
A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies.
RESULTS
Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; =0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; =0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; =0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups.
CONCLUSION
This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.
Topics: Humans; Rosuvastatin Calcium; Ezetimibe; Cholesterol, LDL; Anticholesteremic Agents; Hypercholesterolemia; Drug Therapy, Combination; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Treatment Outcome
PubMed: 38154476
DOI: 10.3349/ymj.2023.0285 -
PloS One 2023Although statins are often discontinued when myalgia arises, a causal relationship may not always exist. How well-tolerated statins are when rechallenge is blinded and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although statins are often discontinued when myalgia arises, a causal relationship may not always exist. How well-tolerated statins are when rechallenge is blinded and controlled is unclear.
METHODS AND FINDINGS
We performed a systematic review and meta-analysis (PROSPERO CRD42023437648) to evaluate the success of statin rechallenge versus matched placebo in those who were previously statin intolerant. Our primary outcome was intolerance; our secondary outcome was the myalgia or global symptom score. Medline, Embase, CINAHL Plus, Scopus, and CENTRAL were searched from inception to May 1, 2023. Eligible trials were randomized controlled trials with parallel or crossover designs examining statin rechallenge in statin-intolerant adults. Two independent reviewers selected studies, extracted data, and assessed risk of bias (Cochrane Collaboration's risk-of-bias tool 1). Relative risk (RR) and mean difference (MD) were estimated using fixed effect Mantel-Haenszel statistics. Of 1,941 studies screened, 8 met our inclusion criteria (8 to 491 participants from Asia, Europe, North America, and Oceana). Compared to placebo, intolerance was more common in statin users [325/906 (36%) vs 233/911 (26%), RR 1.40, 95% CI, 1.23 to 1.60, I2 = 0%, 7 trials, number needed to harm 10] and there was no statistically significant difference in myalgia or global symptom score on a 100-point scale [MD 1.08, 95% CI, -1.51 to 3.67, I2 = 0%, 5 trials]. Limitations include only 1 trial asking participants about intolerable symptoms (vs inferring intolerance from discontinuation or trial withdrawal); the small number of trials; the possibility of attrition bias; and the potential for carryover effects in crossover/n-of-1 trial designs.
CONCLUSIONS
Of those previously intolerant of statins who were rechallenged with a statin and compared to placebo recipients, medication intolerance was more common amongst statin recipients. However, there was no significant difference in mean myalgia or global symptom score between statin and placebo, and only one-third of those previously believed to be statin intolerant were unable to tolerate a statin on blinded rechallenge; one-quarter were intolerant of placebo.
Topics: Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myalgia; Randomized Controlled Trials as Topic; Asia; Europe
PubMed: 38128013
DOI: 10.1371/journal.pone.0295857