Dataset Information

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

ABSTRACT: Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [-0.65 (-0.87 to -0.43), bempedoic acid; -0.43 (-0.67 to -0.20), ezetimibe; -0.28 (-0.48 to -0.08)], and omega-3 fatty acids [omega3FAs, -0.27 (-0.52 to -0.01)]. CRP was reduced by -0.40 (-1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07-0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00-0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.

SUBMITTER: Xie S

PROVIDER: S-EPMC10981526 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Xie Sining S Galimberti Federica F Olmastroni Elena E Luscher Thomas F TF Carugo Stefano S Catapano Alberico L AL Casula Manuela M

Cardiovascular research 20240301 4

Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placeb ...[more]

PMID: 38373008

Similar Datasets

Project description:BackgroundTo evaluate the reductions of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C) in different lipid-lowering drugs, and to assess the relationships between the reductions of CRP, LDL-C, and cardiovascular (CV) events.MethodsWe searched MEDLINE, EMBASE, and Cochrane CENTRAL up to September 1, 2021. Randomized controlled trials (RCTs) comparing statins, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs), or ezetimibe against placebo with a treatment duration of at least 4 weeks and data on the effects of cholesterol-lowering interventions on LDL-C and CRP were included in this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated.ResultsCompared with placebo treatment, statins and ezetimibe treatments resulted in a significant decrease in LDL-C level (statins: WMD -47.94 mg/dL, 95% CI -51.21 to -44.67 mg/dL; ezetimibe: WMD -22.84 mg/dL, 95% CI -26.76 to -18.92 mg/dL) and CRP level (statins: WMD -0.67 mg/L, 95% CI -0.90 to -0.45 mg/dL; ezetimibe: -0.64 mg/L, 95% CI -1.07 to -0.21 mg/dL). Compared with placebo treatment, treatment with PCSK9-mAbs resulted in significant decrease in LDL-C level (WMD -54.24 mg/dL, 95% CI -59.77 to -48.70 mg/dL), while the concentration of CRP did not decrease significantly. Meta-regression analysis showed no significant association between change in CRP level and change in LDL-C level. Subgroup comparisons suggested that treatment with PCSK9-mAbs showed a greater reduction in LDL-C level when compared with the statins group and ezetimibe group, while the risks of CV death, myocardial infarction (MI), and stroke showed no significant differences.ConclusionBased on the current study, our results suggested that statins, ezetimibe, and PCSK9-mAbs are effective in reducing LDL-C levels. Treatment with statins and ezetimibe also demonstrated a significant effect on CRP. The traditional lipid-lowering strategy including statin and ezetimibe showed similar benefit on CV outcomes compared with the PCSK9-mAbs treatment.

Project description:BackgroundBempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients.MethodsRandomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid.ResultsA total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I2 = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I2 = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R2 = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I2 = 0) when compared with statin alone.ConclusionThis study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.

Project description:Importance:Randomized clinical trials (RCTs) of lipid-lowering therapies form the evidence base for national and international guidelines. However, concerns exist that women and older patients are underrepresented in RCTs. Objective:To determine the trends of representation of women and older patients (?65 years) in RCTs of lipid-lowering therapies from 1990 to 2018. Data Sources:The electronic databases of MEDLINE and ClinicalTrials.gov were searched from January 1990 through December 2018. Study Selection:RCTs of lipid-lowering therapies with sample sizes of at least 1000 patients and follow-up periods of at least 1 year were included. Data Extraction and Synthesis:Two independent investigators abstracted the data on a standard data collection form. Main Outcomes and Measures:Patterns of representation of women and older adults were examined overall in lipid-lowering RCTs and according to RCT-level specific characteristics. The participation-to-prevalence ratio (PPR) metric was used to estimate the representation of women compared with their share of disease burden. Results:A total of 60 RCTs with 485?409 participants were included. The median (interquartile range) number of participants per trial was 5264 (1062-27?564). Overall, representation of women was 28.5% (95% CI, 24.4%-32.4%). There was an increase in the enrollment of women from the period 1990 to 1994 (19.5%; 95% CI, 18.4%-20.5%) to the period 2015 to 2018 (33.6%; 95% CI, 33.4%-33.8%) (P for trend?=?.01). Among common limiting factors were inclusion of only postmenopausal women or surgically sterile women (28.3%; 95% CI, 18.5%-40.7%) or exclusion of pregnant (23.3%; 95% CI, 14.4%-35.4%) and lactating (16.6%; 95% CI, 9.3%-28.1%) women. Women were underrepresented compared with their disease burden in lipid RCTs of diabetes (PPR, 0.74), heart failure (PPR, 0.27), stable coronary heart disease (PPR, 0.48), and acute coronary syndrome (PPR, 0.51). Only 23 RCTs with 263?628 participants reported the proportion of older participants. Overall representation of older participants was 46.7% (95% CI, 46.5%-46.9%), which numerically increased from 31.6% (95% CI, 30.8%-32.3%) in the period 1995 to 1998 to 46.2% (95% CI, 46.0%-46.5%) in the period 2015 to 2018 (P for trend?=?.43). A total of 53.0% (95% CI, 41.8%-65.3%) and 36.6% (95% CI, 25.6% to 49.3%) trials reported outcomes according to sex and older participants, respectively, which did not improve over time. Conclusions and Relevance:In this systematic review of RCTs of lipid-lowering therapies, the enrollment of women and older participants increased over time, but women and older participants remained consistently underrepresented. This limits the evidence base for efficacy and safety in these subgroups.

Project description:BackgroundRandomized trials of therapies that primarily lowered triglycerides have not consistently shown reductions in cardiovascular events.MethodsWe performed a systematic review and trial-level meta-regression analysis of 3 classes of lipid-lowering therapies that reduce triglycerides to a greater extent than they do low-density lipoprotein cholesterol (LDL-C): fibrates, niacin, and marine-derived omega-3 fatty acids. Key inclusion criteria were a randomized controlled trial that reported major vascular events. We also incorporated data from a previous meta-regression of 25 statin trials. The main outcome measure was the risk ratio (RR) for major vascular events associated with absolute reductions in lipid parameters.ResultsA total of 197 270 participants from 24 trials of nonstatin therapy with 25 218 major vascular events and 177 088 participants from 25 trials of statin therapy with 20 962 major vascular events were included, for a total of 374 358 patients and 46 180 major cardiovascular events. Starting with non-high-density lipoprotein cholesterol, a surrogate for very-low-density lipoproteins and low-density lipoproteins, the RR per 1-mmol/L reduction in non-high-density lipoprotein cholesterol was 0.79 (95% CI, 0.76-0.82; P<0.0001; 0.78 per 40 mg/dL). In a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for low-density lipoproteins and very-low-density lipoproteins, respectively), the RR was 0.80 (95% CI, 0.76-0.85; P<0.0001) per 1-mmol/L (0.79 per 40 mg/dL) reduction in LDL-C and 0.84 (95% CI, 0.75-0.94; P=0.0026) per 1-mmol/L (0.92 per 40 mg/dL) reduction in triglycerides. REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) was a significant outlier and strongly influential trial in the meta-regression. When removed, the RRs became 0.79 (95% CI, 0.76-0.83; P<0.0001) per 1-mmol/L (0.78 per 40 mg/dL) reduction in LDL-C and 0.91 (95% CI, 0.81-1.006; P=0.06) per 1-mmol/L (0.96 per 40 mg/dL) reduction in triglycerides. In regard to omega-3 dose, each 1 g/d eicosapentaenoic acid administered was associated with a 7% relative risk reduction in major vascular events (RR, 0.93 [95% CI, 0.91-0.95]; P<0.0001), whereas there was no significant association between the dose of docosahexaenoic acid and the relative risk reduction in major vascular events (RR 0.96 [95% CI, 0.89-1.03]).ConclusionsIn randomized controlled trials, triglyceride lowering is associated with a lower risk of major vascular events, even after adjustment for LDL-C lowering, although the effect is less than that for LDL-C and attenuated when REDUCE-IT is excluded. Furthermore, the benefits of marine-derived omega-3 fatty acids, particularly high-dose eicosapentaenoic acid, appear to exceed their lipid-lowering effects.

Project description:BackgroundKuding tea (KT), traditional tea material and widely used in China, has been found to have lipid-lowering effect in clinical and experimental studies. However, there has been no systematic review of the evidence on this subject.MethodsEight electronic databases were searched from database inception until September 2021 for relevant randomized controlled trials (RCTs). We used the Cochrane Reviewer's Handbook to assess the quality of the included studies. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to measure the pooled effect size by random-effects model. Funnel plot, Egger regression test, and the Begg's test was used to assess publication bias.ResultsEight RCTs involving 716 patients were included in our meta-analysis. Comparing with the control group, KT group reduced serum total cholesterol (TC) levels (WMD: -0.56 mmol/L; 95% CI: -0.64, -0.47; I2 = 56.56%; P = 0.00), triglyceride (TG) levels (WMD: -0.30 mmol/L; 95% CI: -0.35, -0.24; I 2 = 88.60%; P = 0.00), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: -0.29 mmol/L; 95% CI: -0.37, -0.21; I2 = 89.43%; P = 0.00), but no significant effects on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.07 mmol/L; 95% CI: -0.02, 0.16; I 2 = 93.92%; P = 0.12). The results of sensitivity analysis were not altered after removing each study in turn. Subgroup analyses showed that KT intervention period was the source of heterogeneity. Following analysis, results revealed that long-term (>4 weeks and ≤8 weeks) use of KT increased HDL-C levels (WMD: 0.19; 95% CI: 0.13, 0.25). In addition, both the sensitivity analysis and subgroup analysis showed that our results were robust. No potentially significant publication bias was found from the funnel plot, Begg-Mazumdar correlation test and Egger regression test.ConclusionKT supplementation can effectively improve lipid profile and KT is a promising approach to reduce blood lipid level in patients with metabolic disorders.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42020221850].

Dataset Information

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Publications

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets