Significant Reduction In Low-density Lipoprotein Cholesterol Levels Research Articles

Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022–January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023–July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated “as soon as possible” in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trial

Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8mmol/L or non-FH patients with screening LDL-C level ≥3.4mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450mg Q4W, tafolecimab 600mg Q6W, placebo 450mg Q4W, or placebo 600mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n=411) or placebo (n=203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]:-65.0% [97.5% CI:-70.2%,-59.9%] for 450mg Q4W;-57.3% [97.5% CI:-64.0%,-50.7%] for 600mg Q6W; both P<0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8mmol/L, and LDL-C < 1.4mmol/L than placebo group at both dose regimens (all P<0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Tafolecimab dosed at 450mg Q4W and 600mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. This study was sponsored by Innovent Biologics, Inc.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

BackgroundHeterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody.MethodsPatients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels.ResultsIn total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: −57.4% [97.5% CI, −69.2 to −45.5] for 150 mg Q2W; −61.9% [−73.4 to −50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension.ConclusionsTafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH.Trial registrationClinicalTrials.gov, NCT04179669.

Abstract 10111: Efficacy and Safety of Tafolecimab in Chinese Patients With Non-Familial Hypercholesterolemia (CREDIT-1): A 48-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial

Introduction: Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust low density lipoprotein cholesterol (LDL-C)-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored. We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (ClinicalTrials.gov, NCT04289285). Methods: Patients were randomized 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W or placebo Q6W for 48 weeks. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Secondary endpoints included proportion of patients achieving ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L. Results: A total of 618 patients (mean LDL-C level 2.85 mmol/L; 9.3% on ezetimibe; 72.8% at very-high cardiovascular risk) were randomized. Of 614 patients receiving at least one dose of the study treatment, 568 (92.5%) completed the study. At both dose regimens, tafolecimab treatment induced significant reductions in LDL-C levels, and significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L compared with corresponding placebo groups ( Table ). Meanwhile, significant reductions in non-high density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) levels were achieved with tafolecimab versus placebo at week 48. The most commonly-reported treatment-emergent adverse events were upper respiratory tract infection, urinary tract infection and hyperuricemia. Conclusions: Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis

BackgroundBempedoic 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). MethodsWe 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. ResultsSeven 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. ConclusionOur 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.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis

BackgroundBempedoic 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). MethodsWe 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. ResultsSeven 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. ConclusionOur 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.

Dyslipidemia in Dialysis Patients.

Dyslipidemia is a well-established traditional risk factor for cardiovascular events in the general population, particularly those with preexisting cardiovascular disease (CVD). In this population, reductions in total and low density lipoprotein cholesterol (LDL-C) levels are effective in reducing coronary artery events and mortality. Dyslipidemia is more common in patients with chronic kidney disease (CKD) and is believed to contribute to the high prevalence of CVD in these patients. To date, the treatment of dyslipidemia in patients with CKD followed the guidelines recommended by the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) for the treatment of lipid abnormalities. These guidelines recommend that initiation of lipid-lowering therapy be based on LDL-C level and the projected 10-year risk for coronary artery disease (CAD). However, we now recognize that the relationship between serum cholesterol and CVD is more complex in patients with CKD, particularly those receiving maintenance hemodialysis. This has been demonstrated by the failure of three large randomized clinical trials to show a beneficial effect of lipid-lowering therapy in reducing mortality in dialysis patients despite significant reduction in LDL-C levels. These results have caused uncertainty among nephrologists about how best to manage dyslipidemia in their patients. In this review, the role of dyslipidemia as a risk factor for atherosclerosis in ESRD patients and the results of the 3 clinical trials and other studies, including their limitations will be discussed, and a schema for treating dyslipidemia in dialysis patients will be proposed.

Simvastatin vs Therapeutic Lifestyle Changes and Supplements: Randomized Primary Prevention Trial

To compare the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). This randomized trial enrolled 74 patients with hypercholesterolemia who met Adult Treatment Panel III criteria for primary prevention using statin therapy. All participants were randomized to an alternative treatment group (AG) or to receive simvastatin (40 mg/d) in this open-label trial conducted between April 1, 2006, and June 30, 2006. The alternative treatment included therapeutic lifestyle changes, ingestion of red yeast rice, and fish oil supplements for 12 weeks. The simvastatin group received medication and traditional counseling. The primary outcome measure was the percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary measures were changes in other lipoproteins and weight loss. There was a statistically significant reduction in LDL-C levels in both the AG (-42.4%+/-15%) (P<.001) and the simvastatin group (-39.6%+/-20%) (P<.001). No significant differences were noted between groups. The AG also demonstrated significant reductions in triglycerides (-29% vs -9.3%; 95% confidence interval, -61 to -11.7; P=.003) and weight (-5.5% vs -0.4%; 95% confidence interval, -5.5 to -3.4; P<.001) compared with the simvastatin group. Lifestyle changes combined with ingestion of red yeast rice and fish oil reduced LDL-C in proportions similar to standard therapy with simvastatin. Pending confirmation in larger trials, this multifactorial, alternative approach to lipid lowering has promise for a subset of patients unwilling or unable to take statins.