Low-intensity Statin Research Articles

Lipid control and stroke risk in atrial fibrillation patients treated with direct oral anticoagulants and statins.

The risk of ischemic stroke and intracerebral hemorrhage (ICH) with intensive lipid control by statins among patients with atrial fibrillation (AF) who require direct oral anticoagulants (DOAC) is unclear. We aimed to determine the risks of ischemic stroke and ICH in AF patients treated with DOAC and statins. In a population-based retrospective cohort study, we identified AF patients concurrently on DOAC and statins from 2015 to 2021 in Hong Kong. Primary outcome was ischemic stroke. Secondary outcomes were ICH and death. We correlated study outcomes with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as time-varying, continuous variables with restricted cubic spline. In secondary analyses, the risks of study outcomes with statin intensity (low, moderate, high) were determined by multivariable time-dependent marginal structural Cox models. We identified 32,752 AF patients co-prescribed with DOAC and statins. Lower LDL-C (p < 0.001) and higher HDL-C (p < 0.001) levels were associated with lower risk of ischemic stroke but not significantly associated with ICH. LDL-C of <1.8 mmol/L (70 mg/dL) was not associated with mortality (19.6% vs 18.4%, difference 1.2% [95% CI -0.35 to 2.13]). High-intensity statin was associated with a lower risk of ischemic stroke compared with low-intensity statin (weighted Cox-specific hazard ratio [95% CI]: 0.82 [0.67-0.99], p = 0.040) independent of LDL-C levels. Similar associations were found in 11,444 AF patients with a history of ischemic stroke. Intensive lipid control by high-intensity statins was associated with a lower risk of ischemic stroke in AF patients who required DOACs and did not appear to increase the risk of ICH.

Redefining Statin Dosage Post-Gastric Bypass: Insights from a Population Pharmacokinetics-Pharmacodynamics Link Approach.

Roux-en-Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic-pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed-effect modeling approach. A parent-metabolite model with first-order absorption, 2-compartments for SV and 1-compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL-cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low-intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post-RYGB patients to maintain a comparable response to that of non-operated subjects. Moderate-intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non-statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post-RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non-statin drugs to attain equivalent responses and mitigate potential adverse events.

Pre-Injury Statin Exposure is Associated With Improved Outcomes in Injured Patients That Receive Whole Blood.

Introduction: Whole blood (WB) is associated with improved mortality while lowering blood product utilization. Furthermore, statin medications are associated with favorable outcomes in traumatic brain injury and risk reduction of venous thromboembolism. However, the use of statin medications has not been evaluated in those receiving WB. The objective of this study is to determine the effects of pre-injury statin exposure on patients receiving WB.Methods: Patients that underwent WB first resuscitation and received pre-injury statins were compared to those that did not receive pre-injury statins. Demographics as well as complication rates, blood product transfusion volumes, and mortality were evaluated. Univariate and multivariable analyses were used to determine independent predictors of mortality.Results: In the study period, 785 patients received WB as part of their resuscitation. One hundred and thirty five patients (17.3%) took statin medications prior to injury. Patients that were exposed to a pre-injury statin had a lower mortality rate than those that were not exposed (21.5% vs 32.5%, P = .01). After adjusting for imbalances, age, ISS, Glasgow Coma Scale, admission systolic blood pressures, and pre-injury statin use were independent predictors of mortality following multiple logistic regression. When evaluating outcomes based on statin intensity, the use of high-intensity statins was associated with lower mortality (OR: .37, 95% CI: .13-.93), whereas moderate and low-intensity statins were not.Conclusion: In patients resuscitated with WB, pre-injury statins use was associated with improved outcomes. Specifically, patients that received high-intensity pre-injury statins appeared to be the population that benefited.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84vs. 0.68, p-value:.008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

The Impact of an Educational Intervention on Enhancing Clinical Knowledge of Physicians and Pharmacists Regarding Statins and Monitoring Parameters: The Experience of a Tertiary Teaching Hospital.

Understanding the latest guideline recommendations is crucial for healthcare professionals to apply statin therapy effectively. Thus, the purpose of this study was to evaluate the efficacy of an educational intervention in enhancing the awareness and understanding of physicians and pharmacists concerning risk assessment of Atherosclerotic cardiovascular disease (ASCVD) and the role of statin therapy. This pre- and post-intervention study was conducted in Sana'a, Yemen's capital city, at the University of Science and Technology Hospital. The study was done between 11/2021-12/2021, and two separate educational sessions were ‎held. The McNemar's test and Wilcoxon signed-rank test were employed as necessary. Participants' awareness of the Framingham CVD risk calculator improved significantly from 40.4% pre-intervention to 78.7% post-intervention. Similarly, understanding of the parameters used in the 10-year ASCVD Risk calculator rose from 46.8% pre-intervention to 76.6% post-intervention. The ability to identify high, moderate, and low-intensity statin therapy, for instance, increased from 34% to 63.8% post-intervention. Regarding statins' contraindications, safety, and efficacy monitoring parameters, pre-intervention knowledge was unsatisfactory, and the educational intervention improved it significantly (p <0.05). For physicians, the median ASCVD risk assessment knowledge score was significantly improved from ‎‎4 (IQR = 3-5) pre-intervention to 7 (6.25-8) immediately post-intervention, while the statin therapy clinical knowledge median score ‎significantly improved from 3 (1.25-6.5) to 9 (7.25-14.75) post-education intervention, p-values were 0.002 and 0.003; respectively. For pharmacists, a similar significant improvement (p <0.05) in the overall knowledge scores for both ASCVD risk ‎assessment and statin therapy was noted. The educational intervention improved participants' knowledge of statin therapy and ASCVD risk assessment. Therefore, further education lectures and training programs through continuing ‎medical ‎education on the up-to-date guidelines' recommendations should be regularly implemented to raise ‎awareness and improve ‎the clinical knowledge and appropriateness of statins use in clinical settings.‎.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort

BackgroundHeterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8–10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. ObjectiveHere, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. MethodsThis was a retrospective and prospective multicenter cohort study (2015–2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. ResultsWe analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (−44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. ConclusionPediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy. We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol. Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo. Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy. British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.

Low-Intensity Statin Plus Ezetimibe Versus Moderate-Intensity Statin for Primary Prevention: A Population-Based Retrospective Cohort Study in Asian Population.

While moderate-intensity statin therapy is recommended for primary prevention, statins may not be utilized at a recommended intensity due to dose-dependent adverse events, especially in an Asian population. However, evidence supporting the use of low-intensity statins in primary prevention is limited. We sought to compare clinical outcomes between a low-intensity statin plus ezetimibe and a moderate-intensity statin for primary prevention. This population-based retrospective cohort study used the Korean nationwide claims database (2002-2019). We included adults without atherosclerotic cardiovascular diseases who received moderate-intensity statins or low-intensity statins plus ezetimibe. The primary outcome was a composite of all-cause mortality, myocardial infarction, and ischemic stroke. The safety outcomes were liver and muscle injuries and new-onset diabetes mellitus (DM). We used standardized inverse probability of treatment weighting (sIPTW) and propensity score matching (PSM). In the sIPTW model, 1717 and 36 683 patients used a low-intensity statin plus ezetimibe and a moderate-intensity statin, respectively. In the PSM model, each group included 1687 patients. Compared with moderate-intensity statin use, low-intensity statin plus ezetimibe use showed similar risks of the primary outcome (hazard ratio [HR] = 0.92, 95% CI = 0.81-1.12 in sIPTW and HR = 1.16, 95% CI = 0.87-1.56 in PSM model). Low-intensity statin plus ezetimibe use was associated with decreased risks of liver and muscle injuries (subHR [sHR] = 0.84, 95% CI = 0.74-0.96 and sHR = 0.87, 95% CI = 0.77-0.97 in sIPTW; sHR = 0.84, 95% CI = 0.72, 0.96 and sHR = 0.82, 95% CI = 0.72-0.94 in PSM model, respectively). For new-onset DM and hospitalization of liver and muscle injuries, no difference was observed. Low-intensity statin plus ezetimibe may be an alternative to moderate-intensity statin for primary prevention. Our findings provide evidence on safety and efficacy of statin therapy in Asian population.

Intensity of statin therapy and primary prevention of cardiovascular in Korean patients with dyslipidemia.

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ± 6.6 months. The mean age of all participants at baseline was 59.2 ± 8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ± mg/dL, the mean duration of taking statins was 337.4 ± 52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression

BackgroundStudies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited. ObjectivesWe evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels MethodsA literature search was performed to identify studies assessing plaque regression from LLTs. The following LLTs groups were included: High-intensity statin (HIS), HIS+ eicosapentaenoic acid (EPA), HIS + ezetimibe, Low-intensity statin (LIS), LIS + EPA, LIS + Ezetimibe, and PCSK9 inhibitors. Our primary outcomes were change in percent atheroma volume (PAV). Secondary outcomes included mean differences in total atheroma volume (TAV), lumen, plaque, and vessel volumes, fibrous cap thickness (FCT), and lipid arc (LA). Subgroup analyses were performed on LLT type and post-treatment LDL-C levels. Meta-regression was performed to control for covariates. ResultsWe identified 51 studies with 9,113 adults (22 % females). LLTs reduced PAV levels (-1.10 % [-1.63, -0.56], p < 0.01), with significant reduction observed with HIS, LIS + ezetimibe, LIS + EPA, and PCSK9 inhibitors. LLTs reduced TAV levels (-5.84 mm3 [-8.64 to -3.04] p < 0.01), mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). LLTs reduced plaque volume and LA and increased FCT. ConclusionThe plaque regression associated with LLTs is observed to be mainly driven by HIS, reducing both TAV and PAV. This suggest that HIS is the most effective LLT for plaque regression Unstructured abstractWe evaluated plaque regression of LLTs from 51 studies. We found that while reduction of PAV (-1.10 % [-1.63, -0.56], p < 0.01) were present across different LLT types, reduction of TAV (-5.84 mm3 [-8.64 to -3.04] p < 0.01) was mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). These results suggest that HIS is the most effective LLT for plaque regression.

Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study.

This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting. Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first. Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77-0.92, P < 0.001] as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups. Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.

Vitamin D was Superior to Omega-3 as a Simvastatin Adjuvant in Improving Blood Lipids and Atherogenic Index in Type-I Dyslipidemic Rats.

Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats. Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function. Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose. We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.

Comparison of the Efficacy of Ezetimibe Combination Therapy and High-Intensity Statin Monotherapy in Type 2 Diabetes.

Low-density lipoprotein cholesterol (LDL-C)-lowering therapy is considerably important in preventing cardiovascular disease (CVD) among patients with diabetes. Studies comparing CVD, stroke, and mortality outcomes of low- or moderate-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy in patients with diabetes remain lacking. This study compared the primary prevention effect of myocardial infarction (MI), stroke, and all-cause death between combination therapy of low- or moderate-intensity statins and ezetimibe and high-intensity statin monotherapy in patients with diabetes using the Korean National Health Insurance claims database. Patients aged ≥20 years with type 2 diabetes and dyslipidemia were enrolled. The combination therapy of low- or moderate-intensity statin and ezetimibe was compared with high-intensity statin monotherapy after a propensity score-matched analysis. The incidence of composite outcomes consisting of MI, stroke, and all-cause death and each component were analyzed. In moderate-intensity statin therapy with ezetimibe combination therapy, LDL-C (74 ± 37.9 mg/dL vs 80.8 ± 38.8 mg/dL, P < .001) and the incidence of composite outcomes were lower (hazard ratio 0.85, 95% CI 0.74-0.98) than those in high-intensity statin monotherapy. Meanwhile, no significant difference was observed in the LDL-C levels and composite outcomes between low-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy. Adding ezetimibe to a moderate-intensity statin in patients with type 2 diabetes has a greater LDL-C-lowering effect and greater primary prevention of composite outcomes than that of high-intensity statin monotherapy.

Lipid-lowering therapy and LDL-C control for primary prevention in persons with diabetes across 90 health systems in the United States

ObjectiveNational guidelines recommend statin therapy for patients with type 2 diabetes. We assessed the extent of moderate- to high-intensity statin therapy utilization in community practice. MethodsWe evaluated lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) levels at baseline and 1-year follow-up in patients aged 40–75 years with type 2 diabetes but without atherosclerotic cardiovascular disease (ASCVD), across 90 health systems in the United States participating in an electronic health record–derived dataset, Cerner Real-World Data. Multivariable logistic regression was used to evaluate factors associated with utilization of moderate- to high-intensity statin. ResultsWe identified 241,232 patients with type 2 diabetes (58.1 % on moderate- to high-intensity statin, 7.0 % on low-intensity statin, and 34.9 % on no statin). Predictors of moderate- to high-intensity statin therapy included retinopathy (adjusted odds ratio [aOR], 1.26; 95 % confidence interval [CI], 1.15–1.38), hypertension (aOR, 1.52; 95 % CI, 1.43–1.61), and stage 3 chronic kidney disease (aOR, 1.14; 95 % CI, 1.07–1.21). Women (aOR, 0.85; 95 % CI, 0.82–0.87), and those with rheumatoid arthritis (aOR, 0.79; 95 % CI, 0.71–0.87), psoriasis (aOR, 0.85; 95 % CI, 0.75–0.96), and hepatitis C (aOR, 0.40; 95 % CI, 0.39–0.46), had reduced odds of moderate- to high-intensity statin treatment. Utilization of ezetimibe was rare (2.0 %). LDL-C control was suboptimal at baseline (37.0 % and 27.9 % had LDL-C ≥100 mg/dL and <70 mg/dL, respectively). At 1-year follow-up, the rate of moderate- to high-intensity statin therapy utilization was 65.3 %. ConclusionIncreased efforts are needed to improve LDL-C control and LLT use for primary prevention of ASCVD in adults with type 2 diabetes, in particular among women and those with risk-enhancing inflammatory conditions.

Lipid assessment and achievement of secondary prevention european society of cardiology guideline targets in patients with atherosclerotic cardiovascular disease with and without depression

Abstract Background Patients who have a diagnosis of atherosclerotic cardiovascular disease (aCVD) who also have depression (Dep) have a worse CV prognosis than those without Dep. Appropriate secondary prevention greatly improves CVD outcomes. The European Society of Cardiology (ESC) provide guideline targets for lipid levels (2016 &amp; 2019). It is unknown how well these targets are achieved and maintained over time in patients with aCVD at a population level and whether this differs in those with and without Dep. Purpose To investigate the assessment of lipid levels and/or achievement of guideline targets in patients with aCVD with and without Dep over an 11-year period. Methods A retrospective observational cohort study of patients with aCVD was conducted on individual-level linked electronic health record data between 2009 &amp;2019 using the all-Wales SAIL databank. Clinical codes were used to identify aCVD and Dep diagnoses, lipid assessments and lipid-lowering therapy (LLT) from GP data. The proportions of those having lipid assessments during each calendar year, lipid levels achieving ESC 2016 guideline targets and current LLT were documented. Results In 2009, the aCVD cohort comprised of 183,275 patients (44% female) with a mean age (70.6 ±12.3 years), of whom 22% had a Dep diagnosis (56.6% female). In 2009, lipid levels were assessed in 63.1% of patients, dropping to 48.3% by 2019 (68.06% Dep, 61.65% non-Dep in 2009 and 51.7% Dep, 46.84% non-Dep in 2019. Table and Figure). Over the period of study an increasing proportion of patients were prescribed High intensity statins (HIS) and a decreasing proportion were prescribed low intensity statin (LIS) and/or Ezetimibe. Dep patients were more likely to be treated with HIS and/or Ezetimibe and less likely to receive LIS throughout compared with non-Dep (table). An increasing trend for lipid targets being achieved was observed between 2009 and 2019 in those being tested (Table and Figure). However, a significantly smaller proportion of those with Dep met the ESC targets vs non-Dep over the period of study (Table and Figure). Conclusion The proportion of aCVD patients having their lipids checked fell progressively between 2009 and 2019, although a greater proportion of those "checked" patients had achieved LDL-C and non-HDL-C targets, although the proportion who met these targets remained low. Despite patients with aCVD and Dep being more likely to have their lipids assessed and to be prescribed more intensive LLT those without Dep, with the "gap" widening over time. Considerable additional effort will be required in the future to meet the more intensive 2019 targets in these very high risk patients.

The impact of statin intensity on long-term outcomes in elderly patients with acute myocardial infarction who have undergone percutaneous coronary intervention

Abstract Background The data regarding long-term clinical outcomes according to statin intensity in elderly patients who have undergone percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) is unclear. Purpose We aimed to investigate the long-term clinical benefit of high intensity statin versus moderate to low intensity statin in elderly patients underwent PCI for acute MI. Methods Among 13104 patients with acute MI who have undergone PCI in a nationwide, prospective, and real-world registry, 4294 elderly (defined as ≥70 years) patients prescribed statin at discharge were included. 1136 patients were prescribed with high intensity statin, and 3158 patients were prescribed with moderate to low intensity statin. The major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, readmission due to heart failure [HF], or definite/probable stent thrombosis [ST]) and the components of MACE were compared in multivariable Cox regression, propensity score (PS) matched, and underwent PS-adjusted analyses. Results During a median follow-up of 998 days, MACE, all-cause death, and cardiac death occurred in 1297 patients (30.2%), 737 patients (17.2%), and 460 patients (10.7%), respectively. The risks of MACE (entire: 26.9% vs. 31.4%, hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.73-0.95, p=0.005; PS-matched: n=2186, 25.3% vs. 30.8%, HR 0.79, 95% CI 0.67-0.94, p=0.008), all-cause death (entire: 14.4% vs. 18.1%, HR 0.78, 95% CI 0.65-0.93, p=0.005; PS-matched: 13.8% vs. 18.9%, HR 0.69, 95% CI 0.57-0.92, p=0.002), cardiac death (entire: 9.5% vs. 11.4%, HR 0.81, 95% CI 0.67-0.97, p=0.042; PS-matched: 8.7% vs. 11.3%, HR 0.77, 95% CI 0.61-0.96, p=0.031), and readmission due to HF (entire: 5.5% vs. 7.5%, HR 0.72, 95% CI 0.55-0.95, p=0.021; PS-matched: 5.7% vs. 8.1%, HR 0.78, 95% CI 0.59-0.96, p=0.017) were significantly decreased in the patients received high intensity statin compared to in those received moderate to low intensity statin. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, and definite/probable ST between the groups. In patients ≥80 years, compared to the moderate to low intensity statin group, high intensity statin group had the reduced rates of MACE, all-cause death, cardiac death, recurrent MI, any revascularization, stroke, readmission due to HF, or definite/probable ST, but insignificantly. Conclusions From the nationwide registry, we noted that in elderly patients after PCI for acute MI the administration of high intensity statin versus moderate to low intensity statin was contributed to the improved long-term clinical outcomes.

Real vs perceived LDL cholesterol control in clinical practice in Spain: Which factors are related to real control?

Abstract Background/Introduction According to ESC Guidelines, low-density lipoprotein cholesterol (LDLc) reduction is essential for the control of dyslipidaemia. Frequently, the physicians’ perception of LDLc control in patients (pts) is higher than the actual control, potentially leading to a suboptimal management of these pts. Purpose To understand the impact of physicians’ perception on LDLc control using a multivariate analysis and identify other potential predictive factors in the management of pts with dyslipidaemia in Spain. Methods Cross-sectional and multicentre study that included 435 healthcare professionals (34% cardiologists, 28% General Practitioners [GPs], 24% internists, and 14% endocrinologists) from 145 healthcare areas in Spain. Qualitative and quantitative information related to the management of pts with dyslipidaemia in clinical practice was collected. Additionally, aggregated anonymized data of the last 10 pts with dyslipidaemia attended by each physician were collected. With these data, a multivariate analysis was performed to estimate the impact of different variables on real LDLc control, including: age, gender and speciality of the physician, category of prevention, presence of comorbidities, lipid-lowing therapy (LLT) used, and whether the physician accurately perceived the real LDLc control. Results 4,010 pts (8%, 13%, 16% and 61% with low, moderate, high, and very high CV risk) were included. Physicians’ perception was that 62% of the pts achieved LDLc goals, but in actual clinical practice only 31% of pts did (p&amp;lt;0.01) (Figure 1). In the multivariate analysis it was found that physicians’ age and gender had little to no effect on LDLc control of pts, while their speciality did: cardiologists were twice as likely to control patients with dyslipidaemia than GPs. Likewise, pts with comorbidities or on secondary prevention were statistically associated with lower chance of appropriate LDLc control. Regarding the treatment used, data showed that the proportion of pts achieving LDLc goals increased as higher potency LLT was used. Precisely, LLT was found to have an significant impact on LDLc control: when compared to low intensity statins, pts treated with the combination of statin + ezetimibe had twice as many chances of achieving LDLc goals, reaching up to almost 15 times more possibilities for pts using PCSK9i. Lastly, control perception also mattered, with physicians who accurately perceived the real control having a probability two times higher to control their pts than physicians with poor LDLc control perception. Conclusions In Spain, most pts with dyslipidemia do not achieve the recommended LDLc goals mainly because of an insufficient intensification of LLT. The multivariate analysis showed that both LLT intensity and physicians’ perception had a major effect on LDLc control. These data highlight the need to further intensify LLT and raise awareness among physicians of the importance of achieving LDLc targets.Perceived vs real LDLc control by riskMultivariate analysis results

LDL cholesterol target attainment in a representative German cohort of high- and very-high-CV risk patients with statin intolerance: a simulation study

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. Reasons include the inability to tolerate sufficient doses of statins. To reduce cardiovascular risk in these patients, alternative lipid-lowering therapies (LLT) are required. Purpose Simulation of LDL-C target attainment and achievable LDL-C reductions with oral LLT including ezetimibe and bempedoic acid in patients with statin intolerance (SI) using electronic health records. Methods Data were obtained from the IQVIATM Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high cardiovascular risk based on ESC/EAS guidelines and diagnosed hypercholesterolaemia. Within this cohort, statin-intolerant patients were classified by applying the following literature-informed definitions pointing towards SI with high confidence (among others): patients with LLT only consisting of non-statins, long-term discontinuation of statin therapy, down-titration of statins, and documented side effects in the electronic health records. We used a Monte Carlo approach to simulate sequentially escalating oral LLT, by adding ezetimibe and bempedoic acid in patients with uncontrolled LDL-C in this population. Results Of the total study population (n=130,778 patients), 33.9% had high and 66.1% had very-high cardiovascular risk. Within this cohort, 11,286 patients (8.6%) met the criteria of SI. Compared to the total study population, in the SI group, there were higher proportions of patients who exhibited atherosclerotic manifestations and who were classified as "very-high cardiovascular risk" (73.7% vs. 66.1%). Their LDL-C levels were slightly higher (105.6 vs. 103.6 mg/dL). 46.5% received a low-intensity statin monotherapy. Ezetimibe, both as monotherapy or in combination, was more frequently prescribed. 12.3% did not receive any LLT (Table). Patients classified as statin-intolerant entered into the simulation model. At baseline, 7.7% were at LDL-C target. In patients without ezetimibe, consecutive treatment with ezetimibe and bempedoic acid increased the calculated proportion of patients at goal to 22.6% and 52.0%. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1% vs. 49.9%). The median LDL-C (IQR) after simulation of ezetimibe and bempedoic acid treatment was 62 (48–84) mg/dL (Figure). Conclusions Patients meeting the definition of SI based on their electronic health records represented 8.6% of the total cohort of the patients with high or very-high cardiovascular risk. In this population, oral combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Abstract 12292: Lipid-Lowering Therapy and LDL-C Control for Primary Prevention in Persons With Diabetes Across 90 Health Systems in the United States

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in persons with type 2 diabetes, and national guidelines recommend statin therapy for primary prevention of ASCVD in persons with type 2 diabetes (T2DM). Aim: To evaluate the degree of utilization of appropriate intensity statin therapy for primary prevention in patients with T2DM in community practice. Methods: We evaluated lipid-lowering therapy (LLT) and LDL-cholesterol (LDL-C) levels in patients aged 40–75 years with T2DM but without atherosclerotic cardiovascular disease (ASCVD), across 90 health systems in the United States participating in an EHR-derived dataset, Cerner Real World Data at baseline and one year follow-up. Multivariable logistic regression was used to evaluate factors associated with guideline-recommended (moderate- to high-intensity) statin therapy use. Results: We identified 241,232 patients with T2DM (58.1% on appropriate statin, 7.0% on low-intensity statin, and 34.9% on no statin. Predictors of appropriate statin therapy included retinopathy (adjusted odds ratio [aOR], 1.26; 95% CI, 1.15–1.38), hypertension [aOR 1.52 (1.43-1.61)], and stage 3 chronic kidney disease [CKD; aOR 1.14(1.07–1.21]. Women (aOR, 0.85, 95% CI, 0.82-0.87), and those with rheumatoid arthritis [aOR, 0.79 (0.71–0.87)], psoriasis [aOR, 0.85 (0.75–0.96)], and hepatitis C [aOR, 0.4 (0.39–0.46)] had reduced odds of appropriate statin treatment. Utilization of ezetimibe was rare (2.0%). LDL-C control was suboptimal (36.9% and 27.9% had LDL-cholesterol ≥100 mg/dL and &lt;70 mg/dL, respectively). Therapy uptitration was infrequent; at one-year only 65.3% of patients were on appropriate statin intensity (Figure). Conclusions: Increased efforts are needed to improve primary prevention of ASCVD in adults with T2DM, particularly among women and those with risk-enhancing inflammatory conditions.

Modifiable Statin Characteristics Associated with Potential Statin-Related Prescribing Cascades.

Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events. We conducted a secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades using MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019. Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study. Herein, we measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CIs) of modifiable statin characteristics after adjusting for baseline characteristics. We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogues (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically-acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94). Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.