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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 -
American Journal of Obstetrics &... Feb 2024We aimed to perform a systematic review and meta-analysis of randomized controlled trials to evaluate the prophylactic use of pravastatin in pregnant women with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to perform a systematic review and meta-analysis of randomized controlled trials to evaluate the prophylactic use of pravastatin in pregnant women with high-risk of preeclampsia.
DATA SOURCES
PubMed, Embase, Cochrane Central, and Web of Science were searched from inception to August 2023 with no language or filters restriction. The references from included studies, previous systematic reviews, and meta-analyses were manually searched for any additional studies.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials comparing pravastatin in any dose with placebo or no treatment in pregnant women with high risk for preeclampsia and up to 20 weeks of gestation were included in this meta-analysis.
METHODS
We used RStudio version 4.2.2 with random effects models to compute pooled risk ratios for prespecified outcomes data. The quality assessment was conducted using version 2 of the Cochrane Risk of Bias Assessment Tool. We also performed a trial sequential analysis to evaluate the reliability of our findings.
RESULTS
We included 3 randomized controlled trials comprising 213 patients, of whom 106 (49.8%) were allocated to the pravastatin group. There was no significant effect of pravastatin on the incidence of preeclampsia (risk ratio, 0.62; 95% confidence interval, 0.33-1.14; P=.12).
CONCLUSION
Our study was unable to demonstrate the benefit of pravastatin for preventing preeclampsia in high-risk pregnant women. Nevertheless, these findings comprised only preliminary studies with a small number of subjects, highlighting the need of well-designed, and adequately powered clinical trials.
Topics: Pregnancy; Humans; Female; Pre-Eclampsia; Pravastatin; Pregnant Women; Reproducibility of Results
PubMed: 38109997
DOI: 10.1016/j.ajogmf.2023.101260 -
Expert Opinion on Drug Safety Feb 2024Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver.
METHODS
RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence.
RESULTS
Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), = 0.16; I = 53%], non-serious adverse events[RR = 1.09(0.97,1.22), = 0.15;I = 61%] and all-cause mortality[RR = 1.01(0.60,1.70), = 0.97;I = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25), = 0.67;I = 73%], cardiac disorders [RR = 0.87(0.66,1.15), = 0.33;I = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00), = 0.05; I = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B.
CONCLUSION
The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127.
Topics: Humans; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Hyperlipidemias; Proprotein Convertase 9; RNA, Small Interfering
PubMed: 38063346
DOI: 10.1080/14740338.2023.2293201 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
Journal of Drugs in Dermatology : JDD Dec 2023Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in cholesterol synthesis. While a rare disorder, malignant transformation to squamous cell carcinoma is seen in up to 11% of cases. Recently, topical cholesterol and topical statin therapy have been suggested as a pathogenesis-directed treatment for porokeratosis.
METHODS
A PubMed/MEDLINE and Embase literature search was performed using the search terms: "porokeratosis" AND "cholesterol" OR "lovastatin" OR "simvastatin" OR "atorvastatin" OR "fluvastatin" OR "pitavastatin" OR "pravastatin" OR "rosuvastatin" OR "statin." Peer-reviewed clinical trials, case series, and case reports of all porokeratosis subtypes were included.
RESULTS
Eleven articles were included in the systematic review and 9 articles in the meta-analysis. The systematic review consisted of an aggregate of 33 patients, most of whom (n=31, 93.9%) applied the treatment twice daily for an average of 9.4 weeks (median=8 weeks), with 93.9% (n=31) experiencing improvement or resolution of porokeratosis. Sixteen patients (48.5%) used lovastatin and 16 (48.5%) used simvastatin with concurrent cholesterol therapy. Mild adverse events including erythema and contact dermatitis were experienced by 12.1% of patients. Our meta-analysis yielded a random effects model supporting a robust reduction in porokeratosis severity (OR = .076, 95% CI [0.022, 0.262]).
CONCLUSION
This underpowered meta-analysis provides limited, preliminary evidence supporting the efficacy of topical cholesterol/statin therapy. Overall, quality studies and aggregated sample size are limited; future large clinical trials are needed to further elucidate the role of topical cholesterol/statin therapy in the treatment of porokeratosis. J Drugs Dermatol. 2023;22(12):1160-1165. doi:10.36849/JDD.7775.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Porokeratosis; Lovastatin; Simvastatin; Cholesterol
PubMed: 38051843
DOI: 10.36849/JDD.7775 -
Current Problems in Cardiology Feb 2024Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies.
MATERIALS AND METHODS
An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes.
RESULTS
Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in %: -25.24; 95 % CI: -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %:-21.28; 95 % CI:-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in %: -23.27; 95 % Cl: -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %:-3.37, 95 % CI:-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR:0.81; 95 % CI:0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR:0.67; 95 % CI:0.50 to 0.88; p = 0.005], and myocardial infarction [RR:0.76; 95 % CI:0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR:0.81; p = 0.15], ACM [RR:0.86; p = 0.46], cardiovascular-related mortality [RR:0.79; p = 0.44], and stroke [RR:0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR:0.80; p = 0.0002], while the risk for gout [RR:1.46; p < 0.0001] and hyperuricemia [RR:1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups.
CONCLUSION
Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Myalgia; Randomized Controlled Trials as Topic; Myocardial Infarction; Angina, Unstable
PubMed: 38043880
DOI: 10.1016/j.cpcardiol.2023.102236 -
Current Problems in Cardiology Feb 2024Clinical guidelines recommend statin use in patients with a vast array of cardiovascular disturbances. However, there is insufficient evidence regarding the concomitant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical guidelines recommend statin use in patients with a vast array of cardiovascular disturbances. However, there is insufficient evidence regarding the concomitant use of omega-3 fatty acids in addition to statins. This meta-analysis aims to uncover the complete effects of this combination therapy on cardiovascular outcomes, lipid biomarkers, inflammatory markers, and plaque markers.
METHODS
A detailed literature search was conducted using PubMed, Cochrane, and MEDLINE databases, and all the relevant studies found up to September 2023 were included. The primary outcomes assessed in this meta-analysis was 1) Composite of fatal and non-fatal myocardial infarction, 2) Composite of fatal and non-fatal stroke, 3) Coronary revascularization, 4) Death due to cardiovascular causes, 5) MACE (Major Adverse Cardiovascular Events), 6) Unstable angina, 7) Hospitalization due to unstable angina, 8) and lipid volume index. Secondary outcomes included lipid markers, hsCRP, EPA levels, and EPA/AA ratio.
RESULTS
14 RCTs were included, featuring a total of 40,991 patients. Patients receiving the omega-3 + statin regimen were associated with a statistically significant decrease in the incidence of MI, MACE, unstable angina, hospitalization due to unstable angina, Total cholesterol levels, triglycerides, hsCRP, and lipid volume index in comparison to their counterparts receiving placebo + statin (P < 0.05). In contrast, our analysis found no statistically significant difference in the incidence of fatal and non-fatal stroke, coronary revascularization, and cardiovascular mortality.
CONCLUSION
Our research reinforces that all patients, regardless of their cardiovascular health, may benefit from adding omega-3 fatty acids to their statin therapy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fatty Acids, Omega-3; Cardiovascular Diseases; C-Reactive Protein; Myocardial Infarction; Stroke; Angina, Unstable
PubMed: 38040215
DOI: 10.1016/j.cpcardiol.2023.102245