Lower Baseline Low-density Lipoprotein Cholesterol Research Articles

Lomitapide: A Medication Use Evaluation and a Formulary Perspective.

Lomitapide is approved for lowering low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemia, which is a rare genetic disorder. The evidence regarding its safety and efficacy from a small clinical trial requires further validation for effectiveness and safety in the real world. This study aimed to use institutional data on the effectiveness and safety of lomitapide to assist in formulating a perspective on adding it to the formulary. This was a retrospective review of patients who were actively prescribed lomitapide at King Abdulaziz Medical City, Riyadh, Saudi Arabia, from 2019 to 2022. Data collection included demographics, confirmed gene mutation results, duration of lomitapide therapy, baseline, on-treatment, last LDL-C levels, percent reduction in LDL-C after 1-3 months of therapy (whichever was first available), other LDL-C lowering therapies used, liver function tests, adverse effects, and compliance. Eight adult patients were included in the review, with a mean age of 25.5 years. Approximately 75% were female, and the duration of treatment with lomitapide ranged from 9 months to 3 years. None of the patients were on continuous LDL apheresis. The mean baseline LDL-C at presentation to our facility was 17.2 mmol/L (range, 11.78-21.97 mmol/L), the mean percent drop in LDL-C with lomitapide was 34.1% (range, 0%-87%), gastrointestinal disturbances were documented in 50% of the patients, and no cases of severe liver toxicities or increase in liver enzymes were seen. In our cohort of adult patients, lomitapide showed an overall modest reduction in LDL-C, with no cases of increase in liver enzymes and documented intolerance, indicating that most patients were likely noncompliant. This review revealed important considerations when reimbursing expensive medications for rare diseases. Real-world evidence in real-time can support healthcare systems in price negotiations and reaching mutual agreements that can eventually improve patient access to care.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Moderate-intensity statin plus ezetimibe vs high-intensity statin according to baseline LDL-C in the treatment of atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING randomized trial

Background and aimsWhether the effect of a combination strategy rather than increasing doses of one drug to lower low-density lipoprotein cholesterol (LDL-C) levels is consistent across baseline LDL-C levels remains uncertain. MethodsIn the RACING trial, which showed a non-inferiority of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) to high-intensity statin (rosuvastatin 20 mg) for the primary outcome (3-year composite of cardiovascular death, major cardiovascular event, or stroke), the heterogeneity in treatment effect according to baseline LDL-C levels was assessed for the primary and secondary outcomes (clinical efficacy and safety). ResultsOf 3780 participants, 2817 participants (74.5%) had LDL-C <100 mg/dL, and 963 participants (25.5%) had LDL-C ≥100 mg/dL. The treatment effect of combination therapy versus high-intensity statin monotherapy was similar among the lower LDL-C subset (8.8% vs. 10.2%; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.67 to 1.08, p = 0.19) and the higher LDL-C subset (10.8% vs. 9.6 %; HR 1.14, 95% CI 0.76 to 1.7, p = 0.53) without a significant interaction (interaction p = 0.22). Of the secondary outcomes, the 1-, 2-, and 3-year achievement of LDL-C <70 mg/dL was greater in the combination therapy group regardless of baseline LDL-C levels. ConclusionsAmong ASCVD patients, there was no heterogeneity in the effect of moderate-intensity statin plus ezetimibe combination therapy in the higher and lower baseline LDL-C levels for the 3-year composite of cardiovascular outcomes.

The prognostic role of the low and very low baseline LDL-C level in outcomes of patients with cardiac revascularization; comparative registry-based cohort design

BackgroundAlthough low-density lipoprotein-cholesterol (LDL-C) level is considered one of the main prognostic factors in patients with coronary artery bypass grafting (CABG), the question about “the lower the better” is still unanswered. We aimed to evaluate and compare the outcomes of patients with CABG and low or very low baseline LDL-C, regardless of statin usage.MethodsIn this registry-based cohort study, 10,218 patients with low/very low (70–100 and ≤ 70 mg/dL) baseline LDL-C who underwent isolated and the first-time CABG without known previous history of cardio-cerebrovascular events, were included and compared. The median follow-up was 73.33 (72.15–74.51) months. Primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE) (consisted of all-cause mortality, acute coronary syndrome, stroke or transient ischemic attack, and the need for repeat revascularization [percutaneous coronary intervention or redo-CABG]). Cox regression analyses before and after the propensity score matching (PSM) model were applied to evaluate and compare outcomes.ResultsThe mean age of the study population was 66.17 ± 9.98 years old and 2506 (24.5%) were women. Diabetes mellitus and a history of cigarette smoking were significantly higher in the very low LDL group (P-value ≤ 0.001). In Cox regression analyses before applying PSM model, both all-cause mortality (14.2% vs. 11.9%, P-value = 0.004 and MACCE (26.0% vs. 23.6%, P-value = 0.006) were significantly higher in the very low LDL group compared to low LDL. However, these results were no longer significant after applying the PSM model (all-cause mortality HR: 1.115 [95% CI: 0.986–1.262], P = 0.083 and MACCE HR: 1.077 [95%CI: 0.984–1.177], P = 0.095). The sensitivity analysis to remove the statin effect demonstrated that very low LDL-C level was correlated to higher risk of all-cause mortality in both unmatched and PSM analyses.ConclusionVery low serum LDL-C levels (≤ 70 mg/dl) could increase long-term all-cause mortality and cardiovascular events in patients who have undergone isolated CABG.

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.

The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial.

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated the clinical benefit of the combination of ezetimibe-simvastatin compared to placebo-simvastatin following acute coronary syndrome (ACS). This review highlights key findings from this study with particular attention to the practice-changing impact on guidelines for low-density lipoprotein cholesterol (LDL-C) reduction after ACS, especially among high-risk populations. Consistent reductions in LDL-C have been reported with newer lipid-lowering therapies (proprotein convertase subtilisin/kexin type 9 inhibitors, cholesterol ester transfer proteins, bempedoic acid) in combination with statin in high-risk subgroups. Since high-risk subgroups remain a focus of guidelines, exploration of high-risk subgroups can help define the optimal use of new therapies. Ezetimibe reduced the LDL-C by 16.7mg/dL compared to placebo at 1year, resulting in a significant reduction in the primary composite endpoint (absolute risk difference 2.0%; relative risk difference 6.4%, hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). The benefits achieved with ezetimibein both LDL-C reduction and the primary clinical composite across 10 pre-specified high-risk subgroups, including the elderly; women; patients with diabetes, prior coronary artery bypass graft, history of stroke, polyvascular disease, low baseline LDL-C, renal dysfunction, prior heart failure, and an elevated TIMI risk score for secondary prevention, were similar or greater than in the corresponding non-high-risk subgroups. Safety events were similar between ezetimibe and placebo across the high-risk subgroups. These data support the addition of ezetimibe to statin therapy in high-risk patients who require additional therapy to lower the LDL-C post-ACS.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Magnitude of low-density lipoprotein reduction and impact on major cardiovascular outcomes.

Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study

BackgroundBenefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI. MethodsIn this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8 mmol/L, blood pressure (BP) <140/90 mmHg and smoking abstinence. ResultsThe strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78–2.50]; 2.45 [1.91–2.99]), having a psychologist in the CR team (1.62 [1.36–1.87]; 2.05 [1.67–2.44]), extended opening hours (2.13 [2.00–2.27]; 1.50 [0.91–2.10]), adequate facilities (1.54 [0.91–2.18]; 1.89 [1.38–2.40]), and having a medical director (1.70 [0.91–2.48]; 1.46 [1.04–1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39–4.51]) and having no history of hypertension (2.93 [2.60–3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66–2.10]; 1.46 [1.14–1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95–2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07–2.88]) and group education (1.92 [1.43–2-42]), and no cardiovascular disease history (2.13 [1.78–2.48]). ConclusionsWe identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C

Patients with low baseline low-density lipoprotein cholesterol (LDL-C) but experiencing recurrent coronary revascularization events have been rarely investigated. In this retrospective cohort study, we enrolled patients undergoing percutaneous coronary intervention...

Association of remnant cholesterol and lipid parameters with new-onset carotid plaque in Chinese population.

BackgroundRemnant lipoprotein cholesterol (RC) is an independent risk factor for cardiovascular disease (CVD). However, the relationships of remnant cholesterol and other conventional lipid parameters with new-onset carotid plaque are not fully understood in the Chinese community-based population.Materials and methodsA total of 872 plaque-free participants (51.39 ± 4.96 years old) with no history of CVD were included in this study. The plasma concentrations of RC were calculated by subtracting low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). Multivariate regression models were used to evaluate and compare the associations between RC and other lipid parameters and new-onset carotid plaque.ResultsAfter a mean 6.77-year follow-up, the incidence of new-onset carotid plaque was 188 (21.56%). RC was significantly associated with new-onset carotid plaque [Odd ratio (OR) = 1.57 per 1 mmol/L increase, 95% confidence interval (CI): 1.03–2.41, p = 0.038]. The highest tertile of RC (T3 group) had the highest risk of new-onset carotid plaque (OR = 2.53, 95% CI: 1.63–3.95). Similar results were seen for increased other lipid parameters, but decreased HDL-C levels. When adding another lipid parameter into the adjusted model with RC simultaneously, only RC remained significantly associated with new-onset carotid plaque after adjusting for other lipid parameters (all p value < 0.005). Furthermore, RC was strongly associated with new-onset carotid plaque in participants with lower baseline LDL-C levels.ConclusionIncreased RC levels were superior to other conventional lipid parameters to be associated with new-onset carotid plaque in the Chinese community-based population. Furthermore, RC should be considered in participants with lower LDL-C levels for the purpose of early atherosclerosis prevention.

Low-Density Lipoprotein Cholesterol and Mortality in Peritoneal Dialysis.

BackgroundIn dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients.MethodsIn this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models.ResultsOf 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72).ConclusionLow and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.

Proprotein convertase subtilisin/kexin type 9 inhibition after acute coronary syndrome or prior myocardial infarction.

Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe reduces major adverse cardiovascular events (MACE) in patients with coronary heart disease. Additional treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may lower LDL-C to levels not achievable with conventional lipid-lowering agents. This review summarizes findings from two large, placebo-controlled trials that evaluated the cardiovascular efficacy of monoclonal antibodies directed against PCSK9, added to background statin therapy, in patients with established atherosclerotic cardiovascular disease (ASCVD) or recent acute coronary syndrome (ACS) and persistent elevation of atherogenic lipoproteins despite statin treatment. The FOURIER trial with evolocumab and the ODYSSEY OUTCOMES trial with alirocumab demonstrated 15% overall reductions in MACE compared to placebo, associated with average achieved LDL-C levels as low as 30-40 mg/dl. Alirocumab treatment was associated with fewer deaths after ACS. Subgroups with large absolute treatment benefit included those with baseline LDL-C ≥100 mg/dl, diabetes, polyvascular or peripheral artery disease, prior coronary bypass surgery, statin intolerance, or elevated lipoprotein(a) levels. No safety concerns arose with use of PCSK9 monoclonal antibodies, even in patients who achieved LDL-C levels below 20 mg/dl. In selected patients with established ASCVD or recent ACS, PCSK9 inhibitors can play an important role in reducing the risk of MACE, and may also reduce the risk of death after ACS.

Abstract 9747: Safety, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of AZD8233, Targeting PCSK9, in Patients with Dyslipidemia

Introduction: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular risk by lowering low-density lipoprotein-cholesterol (LDL-C) levels. AZD8233 is an antisense oligonucleotide in development for the treatment of dyslipidemia. In a single ascending dose study (NCT03593785), AZD8233 was well tolerated and effectively reduced PCSK9 and LDL-C levels in patients with elevated LDL-C. Here, we report results from a multiple ascending dose study of AZD8233. Methods: This was a phase 1, randomized, single-blind, placebo-controlled study (NCT04155645) in patients with dyslipidemia. Participants were receiving statins for ≥ 3 months, had an LDL-C in the range 70-190 mg/dL, and were 18-65 years old. Three cohorts of 11 participants received four subcutaneous injections over an 8-week period (days 1, 8, 29, and 57) of either AZD8233 (15 mg, 30 mg, or 90 mg; n = 8) or placebo (n = 3), and were followed up for 16 weeks post dose. The primary objective was to assess safety and tolerability; secondary objectives included assessment of pharmacokinetics and pharmacodynamics of AZD8233; circulating LDL-C was estimated using the Friedewald formula. Results: Overall, 34 patients were randomized and data are available from 33 patients; 15 were male, the mean age was 58 years, and baseline PCSK9 and LDL-C levels were comparable across treatment groups. Treatment with AZD8233 did not result in any clinically relevant safety or tolerability findings. Peak plasma concentrations of AZD8233 were reached within 0.5 to 5 hours post dosing, followed by a biphasic decline. A decrease from baseline in PCSK9 (69.7%, 79.9%, and 95.3%) and LDL-C levels (63.8%, 65.7%, and 83.3%) was observed at 12 weeks for the AZD8233 15 mg, 30 mg, and 90 mg groups, respectively vs placebo ( Figure ). Conclusions: Multiple doses of AZD8233 were generally safe, well tolerated, and reduced PCSK9 and LDL-C levels in a dose-dependent manner in statin-treated patients with dyslipidemia.

Association between baseline ldl-c and prognosis among patients with coronary artery disease and advanced kidney disease

Abstract Background Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. There are currently no studies examining the association of low baseline LDL-C concentration (&amp;lt;1.8 mmol/L) with mortality among patients with CAD and advanced kidney disease (AKD). We aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients. Methods In this observational study, 803 CAD patients complicated with AKD (eGFR &amp;lt;30 mL/min/1.73 m 2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C &amp;lt;1.8 mmol/L, n=138; LDL-C ≥1.8 mmol/L, n=665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality. Results Among 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (&amp;lt;1.8mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01–1.89). Conclusions Our data demonstrated that among patients with CAD and AKD, a lower baseline LDLC level (&amp;lt;1.8mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was supported by the National Natural Science Foundation of China (Grant No. 81670339 and Grant No. 81970311), Cardiovascular Research Foundation Project of the Chinese Medical Doctor Association (SCRFCMDA201216) and Beijing Lisheng Cardiovascular Health Foundation (LHJJ20141751).

Lipid lowering with bempedoic acid added to a proprotein convertase subtilisin/kexin type 9 inhibitor therapy: A randomized, controlled trial

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. However, some patients receiving PCSK9i therapy might require additional lipid-lowering therapy (LLT) to reach LDL-C goals. Bempedoic acid is an oral, once-daily, ATP-citrate lyase inhibitor that significantly lowers LDL-C in patients with hypercholesterolemia when given alone or as add-on therapy to statins and/or ezetimibe. Assess safety and efficacy of bempedoic acid added to PCSK9i (evolocumab) background therapy in patients with hypercholesterolemia. This phase 2, randomized, double-blind, placebo-controlled study was conducted in three phases: 1.5-month screening/washout period including discontinuation of all LLTs, a 3-month period wherein patients initiated background PCSK9i therapy, and a 2-month treatment period in which patients were randomized 1:1 to receive bempedoic acid 180 mg or placebo once daily while continuing PCSK9i therapy. Of 59 patients randomized, 57 completed the study. Mean baseline LDL-C after 3months of PCSK9i background therapy was 103.1 ± ± 30.4 mg/dL. Bempedoic acid added to background PCSK9i therapy significantly lowered LDL-C by 30.3% (P < .001) vs placebo. Compared with placebo, bempedoic acid significantly lowered apolipoprotein B, non-high-density lipoprotein cholesterol, and total cholesterol (nominal P < .001 for all), and high-sensitivity C-reactive protein (P=.029). When added to background PCSK9i therapy, the safety profile of bempedoic acid was comparable to that observed for placebo. When added to a background of PCSK9i therapy, bempedoic acid significantly lowered LDL-C levels with a safety profile comparable to placebo in patients with hypercholesterolemia.

Association between baseline LDL-C and prognosis among patients with coronary artery disease and advanced kidney disease

BackgroundLower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (< 1.8 mmol/L) and mortality is unknown among patients with CAD and advanced kidney disease (AKD). The current study aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients.MethodsIn this observational study, 803 CAD patients complicated with AKD (eGFR < 30 mL/min/1.73 m2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C < 1.8 mmol/L, n = 138; LDL-C ≥ 1.8 mmol/L, n = 665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality.ResultsAmong 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (< 1.8 mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01–1.89).ConclusionsOur data demonstrated that among patients with CAD and AKD, a lower baseline LDL-C level (< 1.8 mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD.

Pemafibrate decreases triglycerides and small, dense LDL, but increases LDL-C depending on baseline triglycerides and LDL-C in type 2 diabetes patients with hypertriglyceridemia: an observational study

BackgroundPemafibrate, a selective PPARα modulator, has the beneficial effects on serum triglycerides (TGs) and very low density lipoprotein (VLDL), especially in patients with diabetes mellitus or metabolic syndrome. However, its effect on the low density lipoprotein cholesterol (LDL-C) levels is still undefined. LDL-C increased in some cases together with a decrease in TGs, and the profile of lipids, especially LDL-C, during pemafibrate administration was evaluated.MethodsPemafibrate was administered to type 2 diabetes patients with hypertriglyceridemia. Fifty-one type 2 diabetes patients (mean age 62 ± 13 years) with a high rate of hypertension and no renal insufficiency were analyzed. Pemafibrate 0.2 mg (0.1 mg twice daily) was administered, and serum lipids were monitored every 4–8 weeks from 8 weeks before administration to 24 weeks after administration. LDL-C was measured by the direct method. Lipoprotein fractions were measured by electrophoresis (polyacrylamide gel, PAG), and LDL-migration index (LDL-MI) was calculated to estimate small, dense LDL.ResultsPemafibrate reduced serum TGs, midband and VLDL fractions by PAG. Pemafibrate increased LDL-C levels from baseline by 5.3% (− 3.8–19.1, IQR). Patients were divided into 2 groups: LDL-C increase of > 5.3% (group I, n = 25) and < 5.3% (group NI, n = 26) after pemafibrate. Compared to group NI, group I had lower LDL-C (2.53 [1.96–3.26] vs. 3.36 [3.05–3.72] mmol/L, P = 0.0009), higher TGs (3.71 [2.62–6.69] vs. 3.25 [2.64–3.80] mmol/L), lower LDL by PAG (34.2 [14.5, SD] vs. 46.4% [6.5], P = 0.0011), higher VLDL by PAG (28.2 [10.8] vs. 22.0% [5.2], P = 0.0234), and higher LDL-MI (0.421 [0.391–0.450] vs. 0.354 [0.341–0.396], P < 0.0001) at baseline. Pemafibrate decreased LDL-MI in group I, and the differences between the groups disappeared. These results showed contradictory effects of pemafibrate on LDL-C levels, and these effects were dependent on the baseline levels of LDL-C and TGs.ConclusionsPemafibrate significantly reduced TGs, VLDL, midband, and small, dense LDL, but increased LDL-C in diabetes patients with higher baseline TGs and lower baseline LDL-C. Even if pre-dose LDL-C remains in the normal range, pemafibrate improves LDL composition and may reduce cardiovascular disease risk.

Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150mg every 2weeks. Carotid MRI was performed at baseline and 6months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9years; 64% male). Alirocumab led to significant changes in LDL-C (p < 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). At 6months, there was a significant reduction in %LC (mean: - 2.1% [- 3.5, - 0.7], p = 0.005; a 17% reduction from baseline of 9.9%) without significant changes in lumen/wall area or in the inflammatory index Ktrans. Carotid plaque lipid content was reduced by 17% after 6months of PCSK9 inhibition with alirocumab. This was seen before observable changes in lumen or wall areas, which supports pursing plaque lipid content as a more sensitive marker of therapeutic response compared to lumen or wall areas in future technical developments and serial studies.

Hepatitis C Eradication With Direct Acting Antivirals Leads to Significant Increase in Serum Cholesterol Levels

Introduction: Patients with chronic hepatitis C have low serological levels of lipoproteins, low-density lipoprotein cholesterol and total cholesterol. However, chronic hepatitis C is known to increase cardiovascular risk. Lipid dynamics after treatment with direct acting antivirals remains unclear, but an overall decrease in cardiovascular mortality is expected after hepatitis C virus clearance. Aims and methods: In this unicentric retrospective cohort study we evaluated lipid profile behaviour after virus clearance with direct acting antivirals. 100 patients were included, excluding patients with known hypercholesterolemia or previously treated with statins. Lipid profile was assessed before, at the end-of-treatment and one year after end-of-treatment. Results: Overall, there was a significant increase in low-density lipoprotein cholesterol (baseline 87.6 ± 37.6 mg/dL, end-of-treatment 111.1 ± 44.2 mg/dl, p-value 100mg/dl almost duplicated at the end-of-treatment (32.4% to 62.3%). Potential positive predictive factors for a significant low-density lipoprotein cholesterol increase were liver cirrhosis and low baseline low-density lipoprotein cholesterol levels. Conclusion: This study suggests that measurement of lipid profile upon completion of treatment with direct acting antivirals is essential to prevent the underdiagnosis of dyslipidemia and avoid hindering cardiovascular risk improvement after treatment.

Trends and predictors of high-intensity statin therapy and LDL-C goal achievement among Thai patients with acute coronary syndrome

BackgroundPrevious studies on the use of high-intensity statins and low-density lipoprotein cholesterol (LDL-C) goal achievement were mostly conducted in patients with acute coronary syndrome (ACS) receiving care before 2013. We aimed to determine trends and predictors of high-intensity statin therapy and LDL-C goal achievement in a more recent cohort of Thai ACS patients. MethodsWe analyzed data from electronic databases of ACS patients at a tertiary-care, teaching hospital in Thailand between 2013 and 2017. Trends and predictors of high-intensity statin therapy and LDL-C goal achievement after hospital discharge were determined with logistic regression analysis. ResultsAmong 1753 ACS patients, 987 (56.3%) received high-intensity statin at discharge. A higher proportion of ACS patients were prescribed high-intensity statins over time (p=0.033 for linear trend), rising from 10% in 2013 to 88% in 2017. Independent predictors of high-intensity statin therapy included age ≤75 years, a diagnosis of myocardial infarction, receiving P2Y12 inhibitors, and beta-blockers. Within 120 days after discharge, 427 (24.4%) patients had follow-up LDL-C measurements. Overall, 185 (43.3%) patients achieved LDL-C goals based on either of the following criteria: LDL-C <70mg/dL or ≥50% reduction in the baseline LDL-C. There was a non-significant trend (p=0.402 for linear trend) in the proportion of patients achieving LDL-C goals over the study period. Independent predictors of achieving LDL-C goal included high-intensity statin therapy after discharge and lower baseline LDL-C on admission. ConclusionsIn a more recent cohort of Thai ACS patients, a higher proportion of patients were prescribed high-intensity statins before discharge over the study period. However, the proportion of patients who achieved LDL-C goal did not increase accordingly. This finding should promote more discussion among health policy makers to improve statin treatment and quality of care for ACS patients.