Retrospective assessment of the effectiveness of lipid-lowering therapy in patients with hypertriglyceridemia in real-world clinical practice

IntroductionThe 2019 ESC/EAS guidelines introduced stricter low-density lipoprotein cholesterol (LDL-C) targets, particularly for patients at high and very high cardiovascular (CV) risk. However, data on the implementation of these targets in real-world clinical practice—especially in countries with high/very high CV risk—remain limited. The DISCOVERY study aimed to assess LDL-C management, lipid-lowering therapy (LLT) use, and guideline adherence across multiple countries in Central and Eastern Europe and Central Asia.MethodsThis prospective, observational, multicenter study enrolled adult patients with hypercholesterolemia (HCL) from 10 countries grouped into three regions. Data was collected at baseline and after 12 weeks of follow-up. LLT patterns, LDL-C levels, target attainment (both investigator-defined and 2019 ESC/EAS-recommended), and physician adherence to guidelines were analyzed.ResultsA total of 6,447 patients were included; 53.2% were female, and the mean age was 60.5 ± 11.9 years. Most patients (66%) were in secondary prevention. At baseline, 36.8% had been treated with LLT. After the first visit, treatment was changed in 78% of patients, but only 42.4% received high-intensity statins and 9.3% received statin-ezetimibe combinations at follow-up. LDL-C target achievement was poor: only 5.6% of patients met the guideline-recommended LDL-C goals, compared to 45.5% who met physician-defined targets. Among patients with ASCVD, only 3.3% achieved guideline LDL-C targets. The most significant gap was observed between guideline recommendations and physician-set LDL-C goals. No significant difference in LDL-C target attainment was observed between specialists and general practitioners.DiscussionThe DISCOVERY study reveals suboptimal LDL-C control and low adherence to the 2019 ESC/EAS guidelines in routine practice across countries with high/very high CV risk. These findings highlight the urgent need for strategies to improve physician awareness, promote intensive LLT use, and close the gap between guidelines and clinical practice. A paradigm shift toward proactive LDL-C management is essential to reduce residual CV risk in these populations.

High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins 1, 2 . In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level 3 . Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated. The FH Optimal Care of the US (FOCUS) study was designed by The FH Foundation to assess current treatment patterns of FH patients, and allowed us to assess rejection rates of PCSK9 inhibitors in those with FH or ASCVD.

The decreased achievement of therapeutic goal in lipid lowering therapy in obese and diabetic patients in Poland.

Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials.

Background: It is well known that Autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus confer atherosclerotic cardiovascular disease (ASCVD) risk comparable to diabetes mellitus (DM). However, prescribing patterns of lipid-lowering therapy in this population remain underexplored. Hypothesis: Patients with autoimmune disease are less likely to receive statins and non-statin lipid-lowering therapy than those with DM across low-density-lipoprotein-cholesterol (LDL-C) strata. Methods: We conducted a nationwide retrospective cohort study using the TriNetX platform, which provides real-time, deidentified clinical data from electronic health records. Adults (≥18 years) with either rheumatoid arthritis or systemic lupus erythematosus or DM type 1 or 2 and at least one low-density lipoprotein cholesterol value were included. Patients were stratified into six LDL-C categories: <70, 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL. Initiation of lipid-lowering therapy within six months of cholesterol measurement was assessed. Statins included atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin. Non-statin therapies included icosapent ethyl, colesevelam, alirocumab, evolocumab, Bempedoic acid, cholestyramine, Inclisiran, colestipol, ezetimibe, gemfibrozil, omega-3 acid, fenofibrate. Individuals with major ASCVD risk factors, prior major adverse cardiovascular events, known statin intolerance, or liver disease were excluded. Comparisons were made using chi-square tests with significance defined as p<0.05. Results: Among 41,805 patients with autoimmune disease and 427,909 with DM, statin use was significantly lower in the autoimmune group across all LDL-C categories: 23.65% vs 33.44% (<70 mg/dL), 17.65% vs 27.86% (70–99), 14.21% vs 25.41% (100–129), 17.20% vs 28.50% (130–159), 26.00% vs 35.59% (160–189), and 39.15% vs 44.91% (≥190) (all p<0.0001). Non-statin lipid-lowering therapy use was significantly lower in autoimmune patients compared to those with diabetes across all LDL-C tertiles, with the largest differences observed at LDL <70 mg/dL (6.19% vs 10.24%, p<0.0001) and 70–99 mg/dL (4.05% vs 7.06%, p<0.0001). Conclusion: Despite comparable ASCVD risk, patients with autoimmune disease are significantly less likely to receive statins or non-statin lipid-lowering therapy than those with DM across LDL-C levels. These findings show a need for improved cardiovascular prevention in this high-risk population.

IntroductionAn incidental finding of coronary artery calcification (CAC) is a common finding on ungated CT thorax examinations. There is evidence that CAC correlates with formal Agatston calcium scores, and the...

The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Real-world management of familial hypercholesterolemia in paediatric patients: a 3-year follow-up from the LIPIGEN registry.

Remnant cholesterol in atherosclerotic cardiovascular disease: a systematic review and meta-analysis

Introduction: Lipoprotein (a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Screening patterns remain variable and it is unclear what factors are associated with Lp(a) testing, and whether knowing the Lp(a) value changes management. Research Question: To better understand the proportion of Lp(a) testing, factors predicting Lp(a) testing, and impact on management in ASCVD patients. Methods: A retrospective study using electronic medical record data from five health systems in the CardioHealth Alliance and PCORnet® identified a cohort with an ASCVD diagnosis in 5 years prior to the index date. The index date was defined as the date of the first Lp(a) test result in 2019-2021 for those with a Lp(a) test, or the date of a randomly selected outpatient encounter in 2019-2021 for those without a Lp(a) test. Initiation of lipid lowering therapy (LLT) was assessed within 6 months after the index date. Multivariable regression modeling was used to determine factors associated with Lp(a) testing. Results: Among 595,685 ASCVD participants, only 2,588 (0.4%) were tested for Lp(a). In adjusted models, those who were older, Black, or Hispanic were less likely to have Lp(a) testing, while those with familial hypercholesterolemia, ischemic stroke/TIA, PAD, prior LLT, or LDL-C ≥130mg/dL were more likely to be tested (table). Those with elevated Lp(a) (>50mg/dL or >125 nmol/L) were more likely to initiate any LLT (43.9% vs 34.6%, p=0.03), particularly PCSK9i (10.9% vs 4.8%, p<0.01) and ezetimibe (11.5% vs 5.9%, p <0.01) compared to those without elevated Lp(a). Statin initiation remained similar between those with and without elevated Lp(a) (32.1% vs 29.5%, p=0.47). Conclusion: Lp(a) testing in ASCVD patients is infrequent, with evidence of disparities by race and ethnicity. Having elevated Lp(a) was associated with higher initiation of non-statin LLT. However, overall initiation of any LLT after an elevated Lp(a) test was low.

Implications of 2001 cholesterol treatment guidelines based on a retrospective analysis of a high-risk patient cohort

Influence of Preoperative Lipid-Lowering Therapy on Postoperative Outcome in Patients Undergoing Coronary Artery Bypass Grafting

A comparison of low and high dose atorvastatin on lipoproteins and inflammatory cytokines: The protection against nephropathy in diabetes with atorvastatin (panda) trial

We developed a smartphone application, MyGeneRank, to conduct a prospective observational cohort study (NCT03277365) involving the automated generation, communication, and electronic capture of response to a polygenic risk score (PRS) for coronary artery disease (CAD). Adults with a smartphone and an existing 23andMe genetic profiling self-referred to the study. We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid-lowering therapy. 19% (721/3,800) of participants provided complete responses for baseline and follow-up use of lipid-lowering therapy. 20% (n = 19/95) of high CAD PRS vs 7.9% (n = 8/101) of low CAD PRS participants initiated lipid-lowering therapy at follow-up (p-value = 0.002). Both the initiation of statin and non-statin lipid-lowering therapy was associated with degree of CAD PRS: 15.2% (n = 14/92) vs 6.0% (n = 6/100) for statins (p-value = 0.018) and 6.8% (n = 8/118) vs 1.6% (n = 2/123) for non-statins (p-value = 0.022) in high vs low CAD PRS, respectively. High CAD PRS was also associated with earlier initiation of lipid lowering therapy (average age of 52 vs 65 years in high vs low CAD PRS respectively, p-value = 0.007). Overall, degree of CAD PRS was associated with use of any lipid-lowering therapy at follow-up: 42.4% (n = 56/132) vs 28.5% (n = 37/130) (p-value = 0.009). We find that digital communication of personal CAD PRS information is associated with increased and earlier lipid-lowering initiation in individuals of high CAD PRS. Loss to follow-up is the primary limitation of this study. Alternative communication routes, and long-term studies with EHR-based outcomes are needed to understand the generalizability and durability of this finding.

After percutaneous coronary interventions (PCIs), patients remain at high risk of developing recurrent cardiovascular events. Despite advances in interventional cardiology, the correct management of residual low-density lipoprotein cholesterol (LDL-C) risk continues to be crucial for improving long-term outcomes after PCI. However, several observational studies have demonstrated suboptimal LDL-C control, poor adherence to statin therapy, and underutilization of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors in real-world clinical practice despite a strong endorsement from international guidelines. Recent studies have shown that early intensive lipid-lowering therapy stabilizes atheromatous plaque and increases fibrous cap thickness in patients with acute coronary syndrome. This finding emphasizes the importance of achieving therapeutic targets by establishing an effective treatment as early as possible. The aim of this expert opinion paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology is to discuss the management of lipid-lowering therapy in patients undergoing PCIs according to Italian reimbursement policies and regulations, with a particular focus on the discharge phase.