-
1.
Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis.
Masson, W, Lobo, M, Lavalle-Cobo, A, Molinero, G
Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. 2021;(3):117-126
Abstract
BACKGROUND Bempedoic acid is a novel non-statin drug that was developed to treat hyperlipidemia in combination with other lipid-lowering drugs in those patients who need additional lipid lowering. OBJECTIVES (1) To investigate the lipid efficacy of bempedoic acid; (2) to analyze the anti-inflammatory effects of bempedoic acid estimated through high sensitivity C-reactive protein (hsCRP). METHODS We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and hsCRP with a minimum of 4 weeks of follow-up. The primary endpoint was defined as the percentage change in lipids and hsCRP levels measured from baseline to follow-up, comparing groups of subjects on bempedoic acid versus placebo. RESULTS Seven eligible trials of bempedoic acid (3892 patients) were included. The bempedoic acid therapy was associated with a significant reduction in LDL-C levels [-20.3% (CI 95% -23.5 to -17.1)]; I2=43%]. Similarly, a significant percentage reduction in the apolipoprotein B levels [-14.3% (CI 95% -16.4 to -12.1)]; p<0.05; I2=46%], non-HDL-C levels [-15.5% (CI 95% -18.1 to -13.0)]; p<0.05; I2=53%] and hsCRP [-23.4% (CI 95% -32.6 to -14.2)]; p<0.05; I2=69%] was demonstrated with the bempedoic acid use. The sensitivity analysis showed that the results were robust. CONCLUSION Our data suggests that the use of bempedoic acid significantly reduces the levels of all atherogenic lipid markers, including LDL-C, non-HDL-C and apolipoprotein B. Furthermore, considering hsCRP levels, the drug produces an anti-inflammatory effect.
-
2.
Meta-Analysis of Intensive Lipid-Lowering Therapy in Patients With Polyvascular Disease.
Alkhalil, M, Kuzemczak, M, Whitehead, N, Kavvouras, C, Džavík, V
Journal of the American Heart Association. 2021;(5):e017948
Abstract
Background Polyvascular atherosclerotic disease is associated with an increased risk of future cardiovascular events. Intensive lipid-lowering therapy (ILT) may mitigate this risk. The aims of this study-level meta-analysis were to examine the effects of ILT in patients with polyvascular disease and whether baseline low-density lipoprotein cholesterol (LDL-C) may determine the level of benefit. Methods and Results Electronic databases were searched through January 2020 to identify randomized controlled trials of treatments targeting upregulation of LDL-C receptors (ie, statins, ezetimibe, and PCSK9 [proprotein convertase subtilisin-kexin type 9] inhibitors). The primary end point was major adverse vascular events as defined by the included studies. A total of 94 362 patients (14 821 [18.6%] with polyvascular disease) from 7 studies were included. In patients with monovascular disease, ILT was associated with a 13% reduction in the primary end point (rate ratio [RR] 0.87; 95% CI, 0.81-0.93 [P=0.0002]) (absolute RR, 1.8%) compared with less ILT, while patients with polyvascular disease had 15% relative RR (0.85; 95% CI, 0.80-0.90 [P<0.00001]) (absolute RR, 6.5%) (P=0.66 for interaction). When factoring LDL-C, unlike patients with monovascular disease, the relative benefits of ILT, compared with less ILT, in patients with polyvascular disease were comparable with LDL-C >100 mg/dL (RR, 0.85; 95% CI, 0.80-0.90 [P<0.00001]) and LDL-C <100 mg/dL (RR, 0.88; 95% CI, 0.81-0.96 [P=0.003]) (P=0.23 for interaction). Conclusions Patients with polyvascular disease experienced comparable benefits to those with monovascular disease in response to ILT. The benefits of ILT in patients with polyvascular disease were not dependent on baseline LDL-C, challenging the approach of using LDL-C as a prerequisite to commence ILT for this high-risk subgroup.
-
3.
Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials.
Khan, SU, Khan, MU, Valavoor, S, Khan, MS, Okunrintemi, V, Mamas, MA, Leucker, TM, Blaha, MJ, Michos, ED
European journal of preventive cardiology. 2020;(12):1255-1268
-
-
Free full text
-
Abstract
AIMS: The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies. METHODS A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model. RESULTS In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)). CONCLUSION While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.
-
4.
Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Di Minno, A, Lupoli, R, Calcaterra, I, Poggio, P, Forte, F, Spadarella, G, Ambrosino, P, Iannuzzo, G, Di Minno, MND
Journal of the American Heart Association. 2020;(15):e016262
Abstract
Background Bempedoic acid (BA) is a novel lipid-lowering drug. We performed a systematic review and meta-analysis on efficacy and safety of BA compared with standard treatment in patients with hypercholesterolemia. Methods and Results Studies were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Efficacy outcome was represented by percentage changes (mean difference [MD] with pertinent 95% CIs) in total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol, and hs-CRP (high-sensitivity C-reactive protein) in BA patients and controls. Seven studies were included (2767 BA-treated patients and 1469 controls), showing a more significant reduction in low-density lipoprotein cholesterol (MD, -17.5%; 95% CI, -22.9% to -12.0%), total cholesterol (MD, -10.9%; 95% CI, -13.3% to -8.5%), non-high-density lipoprotein cholesterol (MD, -12.3%; 95% CI, -15.3% to -9.20%), apolipoprotein B (MD, -10.6%; 95% CI, -13.2% to -8.02%), and hs-CRP (MD, -13.2%; 95% CI, -16.7% to -9.79%) in BA-treated patients compared with controls. Results were confirmed when separately analyzing studies on patients with high cardiovascular risk, studies on statin-intolerant patients, and studies on patients with hypercholesterolemia on maximally tolerated lipid-lowering therapy. BA-treated subjects reported a higher rate of treatment discontinuation caused by adverse effects, of gout flare, and of increase in uric acid compared with controls. On the other hand, BA-treated patients showed a lower incidence of new-onset diabetes mellitus than controls. Conclusions BA is associated with a significant reduction in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP compared with standard treatment. Documented efficacy is accompanied by an acceptable safety profile.
-
5.
Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: A systematic review and meta-analysis of 48 randomized controlled trials.
Sánchez-García, A, Simental-Mendía, M, Millán-Alanís, JM, Simental-Mendía, LE
Pharmacological research. 2020;:105068
Abstract
Previous studies have suggested additional beneficial effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors including the lipid-lowering effect; however, results on lipid profile are controversial. Thus, this meta-analysis aimed to determine the effect of SGLT2 inhibitors treatment on lipid levels in patients with type 2 diabetes. Randomized controlled trials assessing the impact of SGLT2 inhibitors on lipid parameters were searched in PubMed-MEDLINE, SCOPUS, Web of Science, and Google Scholar databases. Meta-analysis was conducted using a random-effects model and generic inverse variance method. Meta-analysis of 48 randomized controlled trials revealed that SGLT2 inhibitors therapy had a significant increase on total cholesterol (WMD: 0.09 mmol/L, 95 % CI: 0.05, 0.13, I2 = 79 %, p < 0.0001), LDL-cholesterol (WMD: 0.10 mmol/L, 95 % CI: 0.07, 0.12, I2 = 94 %, p < 0.00001), HDL-cholesterol (WMD: 0.06 mmol/L, 95 % CI: 0.05, 0.08, I2 = 99 %, p < 0.00001), and non-HDL-cholesterol (WMD: 0.09 mmol/L, 95 % CI: 0.06, 0.12, I2 = 96 %, p < 0.00001). Additionally, SGLT2 inhibitors administration showed a significant decrease in triglyceride levels (WMD: -0.10 mmol/L, 95 % CI: -0.13, -0.07, I2 = 96 %, p < 0.00001). Finally, no significant alteration was found on LDL/HDL ratio after SGLT2 inhibitors treatment (WMD: -0.01 mmol/L, 95 % CI: -0.05, 0.03, I2 = 99 %, p = 0.65). In conclusion, SGLT2 inhibitors significantly increase total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and HDL-cholesterol, and decrease triglyceride levels.
-
6.
Effects of cardamom supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled clinical trials.
Shekarchizadeh-Esfahani, P, Arab, A, Ghaedi, E, Hadi, A, Jalili, C
Phytotherapy research : PTR. 2020;(3):475-485
Abstract
Cardiovascular disease is a highly prevalent issue worldwide and one of its main manifestations, dyslipidemia, needs more attention. Recent studies have suggested that cardamom has favorable effects beyond lipid lowering, but the result are contradictory. Our objective was to conduct a systematic review and meta-analysis on randomized controlled trials (RCTs) that assessed the effect of cardamom on lipids. The search included PubMed, Scopus, ISI Web of Science, Google Scholar, and the Cochrane library (up to March, 2019) to identify RCTs investigating the effects of cardamom supplementation on serum lipid parameters. Weighted mean differences (WMDs) were pooled using a random-effect model. Meta-analysis of data from five eligible RCTs showed that cardamom supplementation did not significantly change the concentrations of total cholesterol (WMD: -6.11 mg/dl, 95% CI [-13.06, 0.83], I2 = 0.0%), low-density lipoprotein cholesterol (WMD: -4.31 mg/dl, 95% CI [-9.75, 1.13], I2 = 0.0%), or high-density lipoprotein cholesterol (WMD: 1.75 mg/dl, 95% CI [-1.95 to 5.46], I2 = 71.4%). However, a significant reduction was observed in serum triglyceride (TG; WMD: -20.55 mg/dl, 95% CI [-32.48, -8.63], I2 = 0.0%) levels after cardamom supplementation. Cardamom might be able to change TG, but for confirming the results, more studies exclusively on dyslipidemia patients and considering the intake of lipid lowering agents as exclusion criteria are necessary.
-
7.
Effects of intensive lipid-lowering therapy on mortality after coronary bypass surgery: A meta-analysis of 7 randomised trials.
Alkhalil, M
Atherosclerosis. 2020;:75-78
Abstract
BACKGROUND AND AIMS The recent reported analysis from the ODYSSEY OUTCOMES trial showed that patients with previous coronary bypass graft surgery (CABG) had enhanced clinical benefits in response to intensive low-density lipoprotein-cholesterol (LDL-c). Nonetheless, the impact on cardiovascular and all-cause mortality was difficult to ascertain given the relatively small number. METHODS We conducted a meta-analysis investigating the role of more versus less intensive lipid-lowering treatment, taking into consideration the difference in studies duration when reporting treatment effect. RESULTS A significant 14% reduction in deaths from any cause [RR 0.86 (95% CI, 0.74 to 0.99)] and 25% reduction in cardiovascular mortality [RR 0.75, (95% CI, 0.65 to 0.86)] were associated with intensive LDL-c reduction in patients post CABG. Importantly, this reduction was apparent in patients who were stable or developed an acute coronary syndrome following CABG. CONCLUSIONS Patients with previous CABG incurred reduction in all-cause mortality and particularly cardiovascular mortality in response to intensive LDL-c reduction. Patient's clinical presentation following CABG did not modulate the associated benefits with intensive LDL-c reduction. Characterising atherosclerotic disease may help identify other high-risk groups who may benefit maximally from additional lipid-lowering therapies.
-
8.
Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.
Zhao, X, Ma, X, Luo, X, Shi, Z, Deng, Z, Jin, Y, Xiao, Z, Tan, L, Liu, P, Jiang, S, et al
BMC pharmacology & toxicology. 2020;(1):86
Abstract
BACKGROUND Bempedoic 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. METHODS Randomized 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. RESULTS A 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. CONCLUSION This 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.
-
9.
Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia.
Banach, M, Duell, PB, Gotto, AM, Laufs, U, Leiter, LA, Mancini, GBJ, Ray, KK, Flaim, J, Ye, Z, Catapano, AL
JAMA cardiology. 2020;(10):1124-1135
-
-
Free full text
-
Abstract
IMPORTANCE Additional lipid-lowering therapy options are needed for patients who cannot achieve sufficient decreases in low-density lipoprotein cholesterol (LDL-C) levels using statins alone or for those who are statin intolerant. OBJECTIVE To conduct a pooled analysis of phase 3 randomized clinical trials of bempedoic acid vs placebo. DESIGN, SETTING, AND PARTICIPANTS This analysis pooled data from 4 double-blind, placebo-controlled randomized clinical trials conducted from 2016 to 2018. Patients were enrolled in North America and Europe. Eligibility criteria included hypercholesterolemia while receiving stable lipid-lowering therapy and high cardiovascular risk or hypercholesterolemia and statin intolerance. INTERVENTIONS Patients were randomized 2:1 to bempedoic acid, 180 mg (n = 2425), or placebo (n = 1198) once daily for 12 to 52 weeks. MAIN OUTCOMES AND MEASURES Primary efficacy end point was percentage change from baseline in LDL-C level at week 12 in the intention-to-treat population. Patients were parsed into 2 groups according to enrollment criteria: (1) patients with hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) or with heterozygous familial hypercholesterolemia (HeFH) or with both and receiving statins and (2) patients with hypercholesterolemia who were statin intolerant receiving maximally tolerated statins. RESULTS In this analysis of 3623 patients, the overall mean (SD) patient age was 65.5 (9.2) years (similar in both pools). Among patients with ASCVD or HeFH or both, the mean (SD) baseline LDL-C level was 107.6 (32.7) mg/dL. At week 12, the LDL-C level percentage change from baseline was -16.0% with bempedoic acid vs 1.8% with placebo (difference, -17.8%; 95% CI, -19.5% to -16.0%; P < .001). Patients with statin intolerance had a mean (SD) baseline LDL-C level of 144.4 (38.8) mg/dL. The percentage changes in LDL-C levels at week 12 were -23.0% in the bempedoic acid group and 1.5% in the placebo group (difference, -24.5%; 95% CI, -27.8% to -21.1%; P < .001). The decrease in LDL-C levels with bempedoic acid was sustained during long-term follow-up in both pools (patients with ASCVD or HeFH or both receiving a maximally tolerated statin, difference of -12.7% at week 52; patients with statin intolerance, difference of -22.2% at week 24). Decreases in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein levels were greater with bempedoic acid vs placebo. Treatment-emergent adverse events associated more frequently with bempedoic acid than with placebo included increased blood uric acid level (2.1% vs 0.5%), gout (1.4% vs 0.4%), decreased glomerular filtration rate (0.7% vs <0.1%), and increased levels of hepatic enzymes (2.8% vs 1.3%). CONCLUSIONS AND RELEVANCE Bempedoic acid added to maximally tolerated statins, including moderate- or high-intensity statins or no background statin, was associated with decreased LDL-C levels vs placebo in patients with hypercholesterolemia with an acceptable safety profile. As a nonstatin adjunct or statin alternative, bempedoic acid has potential for use in a broad spectrum of patients. TRIAL REGISTRATION ClinicalTrials.gov Identifiers: NCT02666664, NCT02991118, NCT03001076, and NCT02988115.
-
10.
Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials.
Simental-Mendía, LE, Simental-Mendía, M, Sánchez-García, A, Banach, M, Serban, MC, Cicero, AFG, Sahebkar, A
Lipids in health and disease. 2019;(1):88
Abstract
OBJECTIVE The aim of this meta-analysis of randomized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent. METHODS PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched in order to find randomized controlled trials evaluating the effect of ursodeoxycholic acid on lipid profile. A random-effect model and the generic inverse variance weighting method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A random-effects meta-regression model was performed to explore the association between potential confounders and the estimated effect size on plasma lipid concentrations. RESULTS Meta-analysis of 20 treatment arms revealed a significant reduction of total cholesterol following ursodeoxycholic acid treatment (WMD: - 13.85 mg/dL, 95% CI: -21.45, - 6.25, p < 0.001). Nonetheless, LDL-C (WMD: -6.66 mg/dL, 95% CI: -13.99, 0.67, p = 0.075), triglycerides (WMD: - 1.42 mg/dL, 95% CI: -7.51, 4.67, p = 0.648) and HDL-C (WMD: -0.18 mg/dL, 95% CI: -5.23, 4.87, p = 0.944) were not found to be significantly altered by ursodeoxycholic acid administration. In the subgroup of patients with primary biliary cirrhosis, ursodeoxycholic acid reduced total cholesterol (WMD: - 29.86 mg/dL, 95% CI: -47.39, - 12.33, p = 0.001) and LDL-C (WMD: -37.27 mg/dL, 95% CI: -54.16, - 20.38, p < 0.001) concentrations without affecting TG and HDL-C. CONCLUSION This meta-analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis.