LDL-C Reduction Research Articles

Reduction in LDL-C following treatment with inclisiran at 2 months in a single centre lipid clinic cohort

Reduction in LDL-C following treatment with inclisiran at 2 months in a single centre lipid clinic cohort

The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function.

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.

High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany

Background and aimsLow-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany.MethodsPatients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration.ResultsSince all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%).ConclusionIn this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.Graphical abstract

Bempedoic Acid: A Contemporary Review of Its Pharmacology, Efficacy, and Safety Profile, Including Recent Data from the CLEAR Outcomes Clinical Trial.

To provide an updated review of bempedoic acid's clinical application in lowering LDL-C in the setting of statin intolerance and the recent findings in the CLEAR Outcomes trial as well as summarize and synthesize the current state of knowledge regarding bempedoic acid while providing an in-depth analysis of the drug's pharmacological properties, mechanism of action, clinical trials, safety, and efficacy. The CLEAR Outcomes trial has provided evidence to support bempedoic acid as a viable alternative to statins for the primary and secondary prevention of cardiovascular disease. Bempedoic acid is a promising treatment option for patients with hypercholesterolemia who are unable to tolerate statin therapy or require additional LDL-C reduction in the treatment of cardiovascular disease, with the newest lipid-lowering cardiovascular outcomes trials expanding on their generalizability particularly in the inclusion of women.

No Reduction in High Body Mass Index in Subjects at 1 Year Presenting With Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention Despite Significant Reduction in LDL-C

No Reduction in High Body Mass Index in Subjects at 1 Year Presenting With Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention Despite Significant Reduction in LDL-C

Inter-Individual Variability in LDL-C Reductions With Inclisiran—Pooled Data From ORION-10 and ORION-11

Inter-Individual Variability in LDL-C Reductions With Inclisiran—Pooled Data From ORION-10 and ORION-11

#6653 USE OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS IN KIDNEY TRANSPLANT PATIENTS: A MULTI-CENTER STUDY

Abstract Background and Aims Diabetes mellitus (DM) is a frequent complication in kidney transplant (KT) patients, leading to a higher cardiovascular mortality and graft loss. The use of therapies such as Glucagon-like peptide-1 receptor agonist (GLP-1RA) could have benefits in KT, although the experience reported so far is limited. The aim of our study is to describe the effectiveness and safety of GLP-1RA in KT patients. Method Retrospective cohort study of KT with DM who started GLP-1RA in three Spanish hospitals (Puerta del Mar University Hospital, Jerez de la Frontera University Hospital and Puerto Real University Hospital) from February 2016 to July 2022. All patients had a minimum follow-up of 6 months after starting the treatment. Clinical and demographic variables were analyzed. We collected GLP-1RA type and dose. Glomerular filtration rate (eGFR), proteinuria, and weight were collected at the start of treatment and after 6 and 12 months. We analyze glycemic control, blood pressure and lipid profile. Acute rejections (AR), de novo donor-specific antibodies (DSA) and adverse effects were documented. Parametric and non-parametric tests were performed according to the normality of the sample. Results In this period, 102 KT with DM were treated with GLP-1RA from 19/02/2016 to 22/07/2022. At the time of the prescription mean body mass index was 35.8 kg/m2 and the mean weight was 95 kg. Forty-two (44%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62 years and 56% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 47.2 ml min/1.73 m2 and the time post-KT was 47 months. The GLP-1RA mostly prescribed was semaglutide (66.7%). Fifty-five (55%) patients reached the maximum recommended dose of the drug. The maintenance immunosuppressive therapy used was steroids (94.7%), tacrolimus (97.4%), mycophenolate (94.7%) and everolimus (2.6%). Eighty-four KT recipients had a minimum follow-up of 6 months and sixty-four were followed for 12 months. We observed stability in eGFR and a reduction in proteinuria (−19.1 mg/g at 6 months, p = .000 and −46.6 mg/g at 12 months, p = .000) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−7.5 mmHg at 6 months, p = .013 and −7,3 mmHg at 12 months, p = .004) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies. Besides, their doses did not change during the period of the study. In our cohort, body weight significantly reduced (−3.6 Kg at 6 months, p = .000 and −3.6 Kg at 12 months, p = .000). Furthermore, HbA1c decreased (−1.2 mmol/L at 6 months, p = .000 and −1.5 mmol/L at 12 months, p = .000). Notably, insulin dose was also reduced (−2.2 UI/day at 6 months, p = 0.048) but the number of patients with sodium-glucose cotransporter 2 inhibitors increased at 12 months (p = 0.031). Finally, we observed a reduction in total cholesterol (−11.5 mg/dL at 6 months, p = .001 and −15.6 mg/dL at 12 months p = .000) and LDL-c (−9.2 mg/dL at 6 months, p = 0.002 and −16.8 mg/dL at 12 months, p = .000) during the follow-up. However, patients receiving statins and steroids and the dose remained unchanged. Fifteen patients (14.7%) suffered from side effects, mainly nausea and vomiting, and ten patients (9.8%) discontinued the treatment for this reason. No changes in the mycophenolate formulation were made. One patient discontinued the treatment due to the diagnosis of pancreatic cancer 8 months after starting the drug. We did not find differences in the levels or in the dose of tacrolimus. Neither AR episodes nor de novo DSAs development were notified. Conclusion This is the first multicenter study that reports the effectiveness and safety of GLP-1RA in KT patients. Our results support that it can be an option for the management of DM in these patients. Its use is safe and it does not seem to alter tacrolimus trough levels, to induce AR episodes or de novo DSAs development.

#5647 EFFECT OF STATINS ON THE INCIDENCE OF CARDIOVASCULAR EVENTS AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Based on intervention thresholds [1], statins are recommended in kidney transplant recipients (KTRs) who are at high risk for major cardiovascular (CV) events. However, in this population, evidence of statin effectiveness is sparse and non-conclusive. The objective of this study is to assess the effect of statins on CV events in KTRs. Method 613 consecutive KTRs from a single-center cohort were retrospectively included between 2006 and 2019. Exposure to statins (indicated in primary or secondary CV prevention) and atherosclerotic CV events during the study period were comprehensively documented. The primary outcome was the incidence of CV events in all statin users compared to that of non-users, based on the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [2]. In this study, only atherosclerotic events were selected (peripheral vascular stenosis, stroke, myocardial infarction, angina pectoris and transitional ischemic attack). The secondary outcomes were the incidence of CV events (i) in KTRs using statins indicated in primary CV prevention and (ii) in KTRs using statins indicated in secondary CV prevention compared to that of non-users. Cox proportional hazard models including statin exposure as a time-dependent covariate and fitted with inverse probability treatment weighting (IPTW) were used, as well as a multivariable Cox proportional hazard model. Results During a median [interquartile range (IQR)] follow-up period of 4.6 [2.7–10.0] years, CV events occurred in 88 KTRs: 48 (55.5%) KTRs had peripheral vascular stenosis, 24 (27.3%) had myocardial infarction, 12 (13.6%) had stroke, three (3.5%) had angina pectoris and one (1.1%) had a transitional ischemic attack. The incidence of CV events was 24.8 per 1000 person-years. In the Cox models fitted with IPTW, exposure to statins, regardless of the indication or indicated in primary and secondary CV prevention, was not associated with a decrease in CV events: Hazard Ratio (HR) [95% confidence interval (CI)]: 1.22 [0.73–2.03] (P = .435), HR: 1.12 [0.66–1.89] (P = .672), and HR: 2.78 [1.19–6.53] (P = .018), respectively. In the multivariable Cox model, diabetes mellitus was strongly associated with CV events (HR: 4.39 [2.79–6.90], p<0.001), and statin exposure was not (HR: 1.25 [0.78–2.03]). In a subgroup of KTRs exposed to statins after kidney transplantation but not before (n=314), the median [IQR] levels of LDL-c was 3.48 [2.89–4.08] mmol/L when starting statins and 2.74 [2.14–3.35] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.74 [0.60–0.85] mmol/L (p<0.001). The median [IQR] levels of triglyceride was 1.99 [1.47–2.91] mmol/L when starting statins and 1.72 [1.20–2.50] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.27 [0.17–0.42] mmol/l (p<0.001). There were no significant changes in HDL-c levels. Conclusion Despite an improvement in the lipid profile including a reduction of LDL-c and triglyceride levels, statin exposure was not associated with a decrease in CV events in a long-term KTR cohort. Other CV risk factors than dyslipidemia, such as diabetes mellitus, were more likely related to such events.

Mobile health for cardiovascular risk management after cardiac surgery: results of a sub-analysis of The Box 2.0 study.

Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary artery bypass grafting (CABG). To improve cardiovascular risk management, this study evaluated the effects of mobile health (mHealth) on BP and cholesterol levels in patients after standalone CABG. This study is a post hoc analysis of an observational cohort study among 228 adult patients who underwent standalone CABG surgery at a tertiary care hospital in The Netherlands. A total of 117 patients received standard care, and 111 patients underwent an mHealth intervention. This consisted of frequent BP and weight monitoring with regimen adjustment in case of high BP. Primary outcome was difference in systolic BP and LDL-C between baseline and value after three months of follow-up. Mean age in the intervention group was 62.7 years, 98 (88.3%) patients were male. A total of 26 449 mHealth measurements were recorded. At three months, systolic BP decreased by 7.0 mmHg [standard deviation (SD): 15.1] in the intervention group vs. -0.3 mmHg (SD: 17.6; P < 0.00001) in controls; body weight decreased by 1.76 kg (SD: 3.23) in the intervention group vs. -0.31 kg (SD: 2.55; P = 0.002) in controls. Serum LDL-C was significantly lower in the intervention group vs. controls (median: 1.8 vs. 2.0 mmol/L; P = 0.0002). This study showed an association between home monitoring after CABG and a reduction in systolic BP, body weight, and serum LDL-C. The causality of the association between the observed weight loss and decreased LDL-C in intervention group patients remains to be investigated.

Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

AimsIndividuals 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 synthesisWe 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). ConclusionsPCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease. Registration code in prosperoCRD42022339785.

ISTO STUDY - INTENSIV-INTERMEDIATE STATIN THERAPY OBSERVATIONAL STUDY

Objective: lifestyle changes are frequently insufficient to reduce cardiovascular risk (CVR) in patients with dislipidemia. This study aims to characterize the long-term evolution of lipid profile and CVR of patients under primary prevention. Design and method: A retrospective study was performed of outpatients at a Portuguese cardiovascular risk clinic with &gt; 2 CVRF, followed &gt;2 years between 1995 and 2015 (Fig. 1). Intermediate-intensity statin therapy had initiated early, in accordance with the clinićs practice. After written informed consent was obtained, sociodemographic and clinical charecteristics were collected from medical charts, at baseline and last visit. Changes in lipid profile and CV risk scores (FRS, ASCVD, SCORE) were estimated. Associations between HDL-C or LDL-C changes and gender, age, observation times and treatments were assessed through bivariate analysis and multiple linear regression models. Results: Out of 516 participants with mean follow-up of 11.4 +/- 4.3 years, 56.6% were female and and received intermediate-intensity statins. Lipid profile showed statistically significant improvment, including median changes in LDL-C and HDL-C of - 77.0 mg/dl and +19 mg/dl, respectively. CVR also showed statistically significant improvements according to all scores. Statin therapy resulted in a mean HDL-C ncrease of 7.4 mg/dl (independently of gender and other treatments) and a mean LDL-C reduction of 51.8 mg/dl (irrespective of age and other treatments). Conclusions: Results from this long-term real-life study indicate that primary prevention, specifically early and continuous therapy with intermediate-intensity statins as an add-on to lifestyle interventions, was important in obtaining consistent and adequate metabolic correction in patients with additional risk factors.

Consequences of diabetes and high-risk dyslipidemia

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Diabetic patients develop both, microvascular and macrovascular long-term complications, and have double the risk of cardiovascular (CV) disease being the main cause of death. The 97% of diabetic patients are classified as high or very high CV risk. The 2019 ESC guidelines for the managment of dyslipidaemia, classified patients with LDL-c &amp;gt;190 mg/dL as high-risk patients, with the indication of high-intensity statins (LDLc reduction greater than 50% and LDLc below 70 mg/dL). Objective To analyze, in a group of patients with high risk dyslipidaemia (HRD, LDLc &amp;gt;190 mg/dL without secondary cause), the consecuences of its association with type 2 diabetes. Methods Observational retrospective cohort of 153 patients with HRD. We compared 35 diabetic patients (G1) vs 118 non diabetic patients (G2), and we analysed clinical characteristics, cardiovascular risk factor’s (CVRF), tase of cardiovascular disease, the baseline blood test with maximum LDL-c (BT1), lipid profile on the last blood test (BT2) and the effects of lipid-lowering treatment. Results There were no differences in relation to sex. G1 were older (69.2 (±12.8) vs 56.8 (±12.5) years old, p=0.001), had a higher body mass index (BMI) (31.4 (±5.9) vs 28.9 (±4.4) kg/m2, p=0.018), higher number of CVRF (3 CVRF, 54.3% vs 10.2%, p&amp;lt;0.0001, and 4 CVRF, 37.1% vs 0%, p&amp;lt;0.0001). Regarding mayor CV events, 80% develop CV disease vs 38.1% (p&amp;lt;0.0001), and 40% develop early coronary disease (ECD) vs 25% (p&amp;lt;0.0001). In the BT1, G1 presented a more atherogenic lipidogram, lower HDL-c &amp;lt;40-45mg/dL values (22.9% vs 9.3%, p=0.033), higher proportion of triglycerides &amp;gt;150mg/dL (74.3% vs 46.6%, p=0.001), higher proportion of small and dense LDL-c (88.6% vs 62.7%, p=0.004) and a higher proportion of VLDL-c &amp;gt;30mg/dL (74.3% vs 45.8%, p=0.003). There were no differences in lipid-lowering treatment (statin 88.6% vs 86.4%, p= 0.7; ezetimibe 68.6% vs 53.4%, p=0.1) or in the lipid-lowering power of LDL reduction &amp;gt;50% (77.1% vs 70.3%, p=0.4), except for a greater prescription of fibrates in G1 (11.4% vs 1.7%, p=0.027). In BT2, lower rates of HDL-c &amp;lt;40-45mg/dL (34.3% vs 16.1%, p= 0.019) and small and dense LDL-c (80% vs 50.9%) persisted in G1, p=0.002) and a higher proportion of chronic kidney disease (25.8% vs 2.6%, p&amp;lt;0.0001). Conclusions Patients with HRD and diabetes have higher CVRF, a more atherogenic lipid profile that persists despite lipid-lowering treatment, and double the rate of CV disease, were half of these events occurs at early age. This association of CVRF should alert us, implementing an early and agressive prevention treatment of all CVRF.

Alogliptin: a DPP-4 inhibitor modulating adipose tissue insulin resistance and atherogenic lipid.

The purpose of this study is to investigate the regulation of adipose tissue insulin resistance with DPP-4 inhibitors in treatment-naive subjects with T2DM and to examine its relation to other diabetic parameters. A total of 147 subjects were treated with alogliptin 12.5-25mg/day (n = 55), sitagliptin 25-50mg/day (n = 49), or teneligliptin 10-20mg/day (n = 43) monotherapy for 3months. Changes in adipo-IR, a mathematical model used to evaluate adipose tissue insulin resistance, and various diabetic parameters were analyzed in this prospective, non-randomized observational study. Among these three drugs, only alogliptin significantly reduced adipo-IR (-25.9%, p < 0.004) and some lipid parameters, such as LDL-C, T-C/HDL-C, log(TG)/HDL-C, non-HDL-C/HDL-C, and LDL-C/HDL-C. Subjects in the alogliptin group were divided into two groups with distinct changes in adipo-IR. Group A had a significant decrease in adipo-IR (-56.5%, p < 0.00001, n = 28), whereas group B had an insignificant increase (19.1%, p = 0.055, n = 27). Significant reductions in FBG or HbA1c were observed in groups A and B, respectively. Group A also showed significant reductions in HOMA-R, T-C/HDL-C, TG, log(TG)/HDL-C, non-HDL-C/HDL-C, LDL-C/HDL-C, and FFA, as well as increases in QUICKI or HDL-C. In contrast, group B showed significant reductions in QUICKI or LDL-C, and increases in HOMA-R, insulin, HOMA-B, C-peptide, or CPR-index. In contrast to other tested DPP-4 inhibitors, alogliptin demonstrated the ability to down-regulate insulin resistance in adipose tissue, as well as certain atherogenic lipids. This study provides the initial evidence of a DPP-4 inhibitor's potential to regulate adipose tissue insulin resistance. Furthermore, adipo-IR is associated with non-LDL-C lipid parameters instead of glycemic control in those receiving alogliptin.

Oral Presentation Award Winner: LDL-C Reduction in Diabetic Patients after Percutaneous Coronary Intervention: Is There any Difference with Non-diabetic?

Oral Presentation Award Winner: LDL-C Reduction in Diabetic Patients after Percutaneous Coronary Intervention: Is There any Difference with Non-diabetic?

Sex differences in efficacy and safety of PCSK9 monoclonal antibodies: A real-world registry

Background and aimsProprotein convertase subtilisin/kexin 9 monoclonal antibodies (PCSK9 mAbs) reduce low-density lipoprotein (LDL-c) with a favourable safety profile. Available data from PCSK9 antibody trials suggest LDL-c reduction is lower in women compared to men. Data in real-world setting is scarce. The aim of this study was to assess sex differences in efficacy and safety of PCSK9 antibodies in clinical care. MethodsAll patients starting with evolocumab or alirocumab in our lipid clinic were included in a prospective registry. We collected clinical information, including baseline and follow-up mean LDL-C levels after initiation of PCSK9 mAbs treatment. In addition, side effects and PCSK9 mAbs discontinuation were recorded. ResultsWe analysed 436 patients (209 women), mean age 58 ± 11 years. Women had higher baseline LDL-c levels compared to men (4.7 ± 1.6 mmol/L vs 4.1 ± 1.4 mmol/L, p < 0.01). PCSK9 mAbs resulted in less relative LDL-c reduction in women compared to men (50% vs 61% p<0.01), but equal absolute LDL-c reduction (respectively 2.3 ± 1.3 mmol/L vs 2.5 ± 1.1 mmol/L, p = 0.087). Women less often reached LDL-c target levels than men (50% vs 72%). No sex differences were observed in reporting of side effects (women 32% vs men 27% p = 0.26) or PCSK9 mAbs discontinuation (women 13% vs men 10%, p = 0.46). ConclusionsIn clinical practice, PCSK9 mAbs are less effective in reducing LDL-c levels in women compared to men and equally safe, implying the importance of sex differences in PCSK9 metabolism.

Effects of Astaxanthin supplementation on selected metabolic parameters, anthropometric indices, Sirtuin1 and TNF-α levels in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial.

Atherosclerosis can develop as a result of an increase in oxidative stress and concurrently rising levels of inflammation. Astaxanthin (AX), a red fat-soluble pigment classified as a xanthophyll, may be able to prevent the vascular damage induced by free radicals and the activation of inflammatory signaling pathways. The objective of the current study is to assess the effects of AX supplementation on cardiometabolic risk factors in individuals with coronary artery disease (CAD). This randomized double-blind placebo-controlled clinical trial was conducted among 50 CAD patients. Participants were randomly allocated into two groups to intake either AX supplements (12 mg/day) or placebo for 8 weeks. Lipid profile, glycemic parameters, anthropometric indices, body composition, Siruin1 and TNF-α levels were measured at baseline and after 8 weeks. Body composition, glycemic indices, serum levels of TNF-α, Sirtuin1 did not differ substantially between the AX and placebo groups (p > 0.05). The data of AX group showed significant reduction in total cholesterol (-14.95 ± 33.57 mg/dl, p < 0.05) and LDL-C (-14.64 ± 28.27 mg/dl, p < 0.05). However, TG and HDL-C levels could not be affected through AX supplementation. Our results suggest that AX supplementation play a beneficial role in reducing some components of lipid profile levels. However, further clinical investigations in CAD patients are required to obtain more conclusive findings. www.Irct.ir., identifier IRCT20201227049857N1.

Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. Economic evaluation from healthcare system and societal perspectives. Ten diverse urban clinics in India and Pakistan. 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

A Study Of antioxidant capacity of different doses of alcoholic extract of Marticaria Chamomilla flower in comparison with vitamin E in oxidative stressed male rats

This study was conducted to investigate the effect of alcoholic extract of Marticaria chamomilla flowers on the antioxidant status in comparison with vitamin E in male rats. Thirty mature male Albino Wister rats were used in this study, the animals were divided into six groups (5 each), the first group was administered with water only, the second one was subjected to H2O2 0.75% in drinking water. The third group was orally intubated with 50mg/kg vitamin E concurrently with H2O2. The other three groups (T3, T4 and T5) were orally administered with M.Ch.E (40, 80 and 120 mg/kg BW) respectively. Blood samples were taken at zero time and then after 30 days, serum sample were examined for CAT, peroxynitrite radical concentration, TC, TAG, HDL-C, VLDL-C and LDL-C. The results showed a significant elevation in ONOO concentration, TC, TAG, VLDL-C and LDL-C associated with a reduction in CAT and HDL-C in H2O2 treated group in compared with control group, this result may be contributed to oxidative damage associated with long term H2O2 exposure. While other groups (vitamin E group and M.Ch.E treated groups) showed a significant reduction in ONOO concentration, TC, TAG, VLDL-C and LDL-C with an elevation in HDL-C if compared to H2O2 treaded group. This may be contributed to the antioxidant effect of vitamin E and M.Ch.E. However, 120mg/kg BW M.Ch.E treated group recorded the highest positive effect against oxidative stress and its effect seems to be normalizing with vitamin E effect, as well as both groups (vit. E and 120mg/kg BW M.Ch.E) clarified a non-significant different with control group in all experiment parameters. This result pointed to antioxidant effect of M.Ch.E in a dose dependent manner.

Atorvastatin

Atorvastatin