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Nutrition, Metabolism, and... Sep 2023Individuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects... (Meta-Analysis)
Meta-Analysis
AIMS
Individuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.
DATA SYNTHESIS
We performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: -1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: -0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).
CONCLUSIONS
PCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.
REGISTRATION CODE IN PROSPERO
CRD42022339785.
Topics: Humans; PCSK9 Inhibitors; Proprotein Convertase 9; Cholesterol, LDL; Glycated Hemoglobin; Antibodies, Monoclonal, Humanized; Diabetes Mellitus; Cholesterol; Enzyme Inhibitors; Anticholesteremic Agents
PubMed: 37414664
DOI: 10.1016/j.numecd.2023.05.033 -
The Ocular Surface Oct 2022Pterygium is an ultraviolet-related disease characterized by an aberrant, wing-shaped and active wound-healing process. There is nothing quite as disheartening for the... (Review)
Review
5-Fluorouracil in primary, impending recurrent and recurrent pterygium: Systematic review of the efficacy and safety of a surgical adjuvant and intralesional antimetabolite.
Pterygium is an ultraviolet-related disease characterized by an aberrant, wing-shaped and active wound-healing process. There is nothing quite as disheartening for the surgeon or patient as the recurrence of pterygium, and various adjuvants have been studied to ameliorate this. This systematic review provides a comprehensive summary of the efficacy and safety of 5-Fluorouracil (5-FU) as an antimetabolite agent for pterygium management. An appraisal of electronic searches of six databases identified 34 clinical studies reporting recurrence outcomes of 5-FU use in primary, impending recurrent and recurrent pterygia. In vitro and in vivo studies of 5-FU showed dose- and duration-dependent cytostatic and cytotoxic effects in human cells. 5-FU is relatively inexpensive, available, and easy to administer, making it attractive for resource-limited scenarios. However, the published evidence demonstrates a recurrence rate of 11.4-60% with the bare scleral technique, 3.5-35.8% with conjunctival rotational flaps, 3.7-9.6% with conjunctival autografts for intraoperative topical 5-FU, and 14-35.8% for preoperative and intraoperative injections. This suboptimal efficacy brings the role of 5-FU as an adjuvant for pterygium surgery into question and the authors do not recommend its use. In contrast, postoperative intralesional injections of 5-FU to arrest progression in impending recurrent pterygium and true recurrent pterygia were more promising, with success rates of 87.2-100% and 75-100%, respectively. Furthermore, 5-FU as a treatment modality, without surgery, effectively arrested progression in 81.3-96% of primary and recurrent pterygia. Other treatments such as topical and intralesional corticosteroids, cyclosporine and anti-VEGF agents are discussed. Complications of 5-FU increase with higher doses and range from transient and reversible to severe and sight-threatening. For pterygium, 5-FU has a predilection for causing scleral thinning, corneal toxicity, and graft-related complications. Additional study with extended follow-up is needed to elucidate the optimal dose, frequency, duration, and long-term safety of 5-FU injections. If 5-FU is used in the management of pterygium, it should be with caution, in selected patients and with vigilant long-term monitoring.
Topics: Humans; Pterygium; Antimetabolites; Fluorouracil; Recurrence; Conjunctiva; Immunosuppressive Agents; Injections, Intralesional; Follow-Up Studies; Treatment Outcome
PubMed: 35961535
DOI: 10.1016/j.jtos.2022.08.002 -
Journal of Affective Disorders Mar 2021Evidence regarding whether statin use is associated with depression is inconsistent. Therefore, we performed a meta-analysis to investigate this association. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence regarding whether statin use is associated with depression is inconsistent. Therefore, we performed a meta-analysis to investigate this association.
METHODS
We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published by March 31, 2020. The Newcastle-Ottawa scale for observational studies was used to assess study quality. All included studies were evaluated by 2 reviewers independently; any discrepancies were resolved through discussion. Because of the heterogeneity of study populations, a random effects model was used to calculate the pooled effect size. Statistical heterogeneity across studies was assessed using the I statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software.
RESULTS
A total of 13 observational (9 cohort, 3 case-control, and 1 cross-sectional) studies conducted in 11 countries and enrolling 5 035 070 participants were included. Substantial statistical heterogeneity was discovered (I, 83%). Overall, use of statins was not associated with depression after trim and fill analysis (adjusted pooled odds ratio [OR], 0.87; 95% CI, 0.74-1.02). The finding was consistent in the subgroup analysis, except for studies published before 2013, showing statin use was associated with a lower risk of depression.
LIMITATIONS
High heterogeneity and asymmetry funnel plot of ORs from these studies were observed.
CONCLUSIONS
This meta-analysis revealed statin use was not associated with depression. However, high heterogeneity was observed between identified studies, and results were inconsistent in the subgroups of studies published before 2013.
Topics: Case-Control Studies; Cross-Sectional Studies; Depression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Odds Ratio
PubMed: 33421857
DOI: 10.1016/j.jad.2020.12.164 -
American Journal of TherapeuticsFindings on the association of statin use with delirium risk are inconsistent. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Findings on the association of statin use with delirium risk are inconsistent.
THE STUDY QUESTION
Is statin use associated with delirium risk?
STUDY DESIGN
We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles in English published until December 31, 2021. The effect size and 95% confidence interval (CI) were defined as the odds ratio (OR) and 95% CI, respectively, to indicate the difference in the incidence of delirium between statin use and nonuse groups. A random-effects model was selected in the case of high heterogeneity of study populations. We used funnel plots, Egger test, Duval and Tweedie trim-and-fill approach, and the classic fail-safe N to assess publication bias.
RESULTS
Of a total of 264 identified studies, 13 were selected for the qualitative review-4 RCTs and 9 observational cohort studies. Statin use was not associated with low delirium risk (pooled OR, 0·82; 95% CI, 0·64-1·04; P = 0·09). Substantial statistical heterogeneity was observed ( I2 , 90%). Visual inspection of the funnel plot of ORs from the studies revealed symmetry. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, we assigned the evidence a rating of C and a weak recommendation for this review.
CONCLUSIONS
Statin use is not associated with delirium risk. More comprehensive RCTs are required to confirm the results.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Odds Ratio; Delirium
PubMed: 36728521
DOI: 10.1097/MJT.0000000000001593 -
Medicine Oct 2022The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear.
METHODS
According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total atheroma volume (TAV), and the secondary outcomes were changes and differences in plaque composition and lipid content.
RESULTS
Data were collected from 9 trials, involving 917 patients who received ezetimibe, evolocumab or alirocumab in addition to a statin and 919 patients who received statins alone. The pooled estimate demonstrated a significant reduction in TAV with the addition of ezetimibe and favorable effects of evolocumab and alirocumab on TAV. Subgroup analysis also supported favorable effects of evolocumab and alirocumab on TAV, according to baseline TAV, gender, type 2 diabetes mellitus, and prior stain use. Addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), but not in high-density lipoprotein cholesterol (HDL-C). The pooled estimate also showed significant favorable effects of ezetimibe on LDL-C, TC, and TG, but an insignificant effect on HDL-C. Patients who received ezetimibe showed similar changes in the necrotic core, fibro-fatty plaque, fibrous plaque, and dense calcification compared with patients not treated with ezetimibe.
CONCLUSIONS
The addition of ezetimibe to statin therapy may further reduce plaque and lipid burdens but may not modify plaque composition. Although current evidence supports a similar impact from the addition of PCSK9 inhibitors to statin therapy, more evidence is needed to confirm such an effect.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; PCSK9 Inhibitors; Plaque, Atherosclerotic; Proprotein Convertase 9; Subtilisins; Triglycerides; Ultrasonography, Interventional
PubMed: 36254013
DOI: 10.1097/MD.0000000000031199 -
Atherosclerosis Jun 2021Statins are the drugs of choice for decreasing elevated low-density lipoprotein cholesterol. Based mostly on animal studies and case reports, they are forbidden to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Statins are the drugs of choice for decreasing elevated low-density lipoprotein cholesterol. Based mostly on animal studies and case reports, they are forbidden to pregnant women and in the preconception period because of their possible teratogenic effects, for which causality has never been proven. The aim of this study was to systematically review the existing studies and to perform a meta-analysis on this topic.
METHODS
The databases PubMed/MEDLINE, Scopus, and Web of Science were searched since the inception until May 16, 2020. The risk of bias for each clinical trial was evaluated using the Cochrane handbook criteria for systematic reviews. The National Institutes of Health (NIH) quality assessment tool was used for the evaluation of cohort and cross-sectional studies. Meta-analysis was performed on the extracted data. Heterogeneity was assessed using I measure and Cochrane's Q statistic. We calculated a pooled estimate of odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model.
RESULTS
23 studies (nine cohort studies, six case reports, six case series, one population-based case-referent study and one clinical trial) with 1,276,973 participants were included in the systematic review and 6 of them (n = 1,267,240 participants) were included in meta-analysis. The results of the critical review did not suggest a clear-cut answer to the question whether statin treatment during pregnancy is associated with an increased rate of birth defects or not, while the results of the meta-analysis indicated that statin use does not increase birth defects [OR (95%CI): 1.48 (0.90, 2.42), p = 0.509], including cardiac anomalies [2.53 (0.81, 7.93), p = 0.112] and other congenital anomalies [1.19 (0.70, 2.03), p = 0.509)].
CONCLUSIONS
We observed no significant increase of birth defects after statin therapy. Thus, there is still no undoubtful evidence that statin treatment during pregnancy is teratogenic, and this issue still needs to be investigated, especially there are more and more pregnant women at high CVD risk that could have benefited from the statin therapy.
Topics: Cholesterol; Cholesterol, LDL; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pregnancy; United States
PubMed: 34044205
DOI: 10.1016/j.atherosclerosis.2021.05.006 -
Indian Heart Journal 2023The benefit of prior statin use to reduce the incidence of arrhythmia in acute coronary syndrome (ACS) is still a matter of debate. Statins have multiple pleiotropic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The benefit of prior statin use to reduce the incidence of arrhythmia in acute coronary syndrome (ACS) is still a matter of debate. Statins have multiple pleiotropic effects, which may reduce the incidence of in-hospital arrhythmia. A systematic review and meta-analysis were performed to evaluate prior statin use and the incidence of in-hospital arrhythmia in ACS.
METHODS
This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We performed a literature search through Pubmed, Proquest, EBSCOhost, and Clinicaltrial.gov. A random-effect model was used due to moderate heterogeneity. Quality assessment was performed using Newcastle Ottawa Scale. Sensitivity analysis was performed by using leave one or two out method. PROSPERO registration number: CRD42022336402.
RESULTS
Nine eligible studies consisting of 86,795 patients were included. A total of 22,130 (25.5%) patients were in statin use before the index ACS event. The prevalence of old myocardial infarction, heart failure, hypertension, diabetes mellitus, and chronic renal failure and concomitant treatment with aspirin, clopidogrel, and beta blocker was higher in the prior statin group compared to no previous statin. Overall, prior statin use was associated with a significantly lower incidence of in-hospital arrhythmia during ACS compared to no previous statin (OR 0.60; 95% CI 0.49-0.72; P < 0.00001; I = 54%, P-heterogeneity = 0.03). In subgroup analysis, previous statin use reduced the incidence of atrial fibrillation or atrial flutter (OR 0.64; 95% CI 0.43-0.95; P = 0.03; I = 73%, P-heterogeneity = 0.01) and ventricular tachycardia or ventricular fibrillation (OR 0.57; 95% CI 0.49-0.65; P < 0.00001; I = 8%, P-heterogeneity = 0.35).
CONCLUSIONS
Based on aggregate patient data, prior statin use may reduce the incidence of in-hospital arrhythmia during ACS, particularly atrial fibrillation or atrial flutter and ventricular tachycardia or ventricular fibrillation.
Topics: Humans; Atrial Fibrillation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Acute Coronary Syndrome; Incidence; Atrial Flutter; Ventricular Fibrillation; Tachycardia, Ventricular
PubMed: 36642406
DOI: 10.1016/j.ihj.2023.01.004 -
Circulation. Cardiovascular Quality and... Aug 2019It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy.
METHODS AND RESULTS
We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79-0.88; P<0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76-0.90; P<0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85-0.96; P<0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73-0.90; P<0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%).
CONCLUSIONS
In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.
Topics: Aged; Cardiovascular Diseases; Clinical Decision-Making; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Male; Middle Aged; Patient Selection; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 31412729
DOI: 10.1161/CIRCOUTCOMES.118.005460 -
Heart Failure Reviews Jan 2023Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot... (Meta-Analysis)
Meta-Analysis Review
Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI - 119.15 to - 46.07; I = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1 month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.
Topics: Adult; Humans; Heart Transplantation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; PCSK9 Inhibitors; Cholesterol, LDL
PubMed: 35687219
DOI: 10.1007/s10741-022-10255-5 -
Viruses Feb 2024Previous studies reported that the association between statins use and influenza infection was contradictory. A systematic review and meta-analysis of longitudinal... (Meta-Analysis)
Meta-Analysis Review
Previous studies reported that the association between statins use and influenza infection was contradictory. A systematic review and meta-analysis of longitudinal studies were performed to determine the association between statins use and influenza susceptibility. The literature search was conducted in PubMed, Embase, and Web of Science, from each database's inception to 21 May 2023. The fixed effect model and random effects model were used for data synthesis. In our study, a total of 1,472,239 statins users and 1,486,881 statins non-users from five articles were included. The pooled risk ratio (RR) of all included participants was 1.05 (95% CI: 1.03-1.07), and there were still significant differences after adjusting for vaccination status. Of note, RR values in statins users were 1.06 (95% CI: 1.03-1.08) in people aged ≥60 years old and 1.05 (95% CI: 1.03-1.07) in participant groups with a higher proportion of females. Administration of statins might be associated with an increased risk of influenza infection, especially among females and elderly people. For those people using statins, we should pay more attention to surveillance of their health conditions and take measures to prevent influenza infection.
Topics: Aged; Female; Humans; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Influenza, Human; Longitudinal Studies
PubMed: 38400053
DOI: 10.3390/v16020278