Moderate-intensity Statin Therapy Research Articles

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.

Comparative effectiveness of moderate-intensity statin with ezetimibe therapy versus high-intensity statin monotherapy in patients with acute coronary syndrome: a nationwide cohort study

The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78–0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice.

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.

Comparative Analysis of High-Intensity versus Low-to-Moderate Intensity Statin Therapy in Patients Undergoing Rotational Atherectomy for Calcified Coronary Artery Disease.

(1) Background: Moderate-intensity statin therapy, when compared to high-intensity statin therapy in Asian populations, has shown no significant difference in cardiovascular prognosis in small studies. The aim of this study was to compare the prognosis of patients based on statin intensity following rotational atherectomy (RA) during high-complexity percutaneous coronary intervention (PCI). (2) Methods: The ROCK registry, a multicenter retrospective study, included patients who had undergone rotational atherectomy (RA) during percutaneous coronary intervention (PCI) at nine tertiary medical centers in South Korea between January 2010 and October 2019. The patients were divided into high-intensity statin (H-statin) and moderate/low-intensity statin (M/L-statin) therapy groups. The primary endpoint includes outcomes (cardiac death, target vessel myocardial infarction (MI), and target vessel revascularization (TVR)) within an 18-month follow-up period. (3) Results: In this registry, a total of 540 patients with 583 lesions were included. We excluded 39 lesions from the analysis due to the absence of statin usage. The H-statin group had 394 lesions and the M/L-statin group had 150 lesions. There were no significant differences in baseline characteristics, procedural adverse events without heart failure history, triglycerides, or medications between the two groups. The procedural success rate showed a significant difference between the two groups. Multivariate analysis did not show a significant association between M/L-statin therapy and an increased risk of the primary endpoint. In propensity score matching analysis, no significant difference was observed in the primary endpoint either. (4) Conclusions: In high-complex RA PCI, moderate/low-intensity statin therapy is not inferior to high-intensity statin therapy in Korea.

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.

Moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy according to baseline LDL-C levels: a prespecified subgroup analysis of RACING Trial

Abstract Aims To compare the effects of moderate-intensity statin plus ezetimibe combination therapy to high-intensity statin monotherapy based on baseline low-density lipoprotein cholesterol (LDL-C) levels. Methods and results In the RACING trial, 3780 atherosclerotic cardiovascular disease (ASCVD) patients were randomly assigned to moderate-intensity statin plus ezetimibe combination therapy or high-intensity statin monotherapy based on baseline LDL-C levels of &amp;lt;100 mg/dL (n=2817) or ≥100 mg/dL (n=963). In the prespecified analysis, the primary outcome (a composite of cardiovascular death, major cardiovascular event, or stroke at 3 years) and key secondary outcome (achievement of LDL-C &amp;lt;70 mg/dL) were reported according to baseline LDL-C levels. The occurrence of the primary outcome did not differ between the combination therapy and the monotherapy groups among those with lower and higher baseline LDL-C levels (8.6% versus 10.1%, hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.37 to 1.09; and 10.5% versus 9.3%, HR 1.13, 95% CI 0.76 to 1.70, respectively) without an interaction (P=0.232). The 1-, 2-, and 3-year achievement of LDL-C &amp;lt;70 mg/dL was greater in the combination therapy group, regardless of baseline LDL-C levels. For secondary safety outcomes, no significant interactions between the treatment strategies and baseline LDL-C levels were found. Conclusion Among ASCVD patients, the effect of moderate-intensity statin plus ezetimibe combination therapy was consistent across the baseline LDL-C levels for the 3-year composite of cardiovascular death, major cardiovascular event, or stroke, and even associated with greater achievement of LDL-C &amp;lt;70 mg/dL compared to high-intensity statin monotherapy.

Dyslipidaemia and its management in patients with type 2 diabetes across the Middle East and Africa: the PACT-MEA study

Abstract Background There is a scarcity of high-quality epidemiological data on the clinical burden of type 2 diabetes (T2D) and cardiovascular risk (CV) in the Middle East and Africa due to under-representation of these regions in contemporary diabetes and cardiovascular trials. Multiple risk factors, including dyslipidaemia, increase CV risk in patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) and those at risk for ASCVD. According to the European Society of Cardiology (ESC) 2021 Guidelines, target low-density lipoprotein cholesterol (LDL-C) for patients with T2D is &amp;lt;1.8 mmol/L (&amp;lt;1.4 mmol/L in patients with eASCVD or at very high risk). Purpose To establish the status of dyslipidaemia and its management in patients with T2D and eASCVD or high/very high ASCVD risk across the Middle East and Africa. Methods Adult patients with T2D participating in a cross-sectional, observational study in seven Middle East and African countries were included in the analysis. Laboratory and medication data were collected from medical charts of patients attending a routine health visit in 2022. Descriptive statistics were used to characterize the lipid profile and management of patients with T2D by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results There were 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), almost all of whom were at high (69%)/very high (30%, includes eASCVD) risk according to ESC 2021 guidelines. In patients for whom data was available in the medical record, median LDL-C (n=2525) was 2.2 mmol/L (IQR, 1.7 to 3.0), HDL-C (n=2453) was 1.1 mmol/L (IQR, 0.9 to 1.3), and triglycerides (n=2488) were 1.6 mmol/L (IQR, 1.2 to 2.3). Of the patients with high/very high ASCVD risk (n=2313), 30% met the ESC guideline-recommended target for LDL-C of &amp;lt;1.8 mmol/L and 16% met the target of &amp;lt;1.4mmol/L. Most patients were on statin therapy (77%, range across countries: 60%-87%, Table 1), with use increasing with age and duration of diabetes. More patients with T2D for ≥10 years were on high intensity statin therapy than those with T2D &amp;lt;10 years (37% vs 33%). A similar pattern was observed for patients with HbA1c levels ≥7% (37% vs 31%, Table 2). Most patients with nephropathy were on statins (87%); use increased with lower eGFR and higher UACR levels. Very few patients were on Ezetimibe (6.4%), fibrates (4.8%), fish oil (including icosapent ethyl) (1.4%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (0.5%). Conclusions Utilization of moderate intensity statin therapy (less than 50% LDL reduction) despite high and very high CV risk leads to failure to achieve cardioprotective LDL targets in most patients. Given the high burden of ASCVD in patients with T2D, prioritization of high intensity lipid lowering therapy is recommended.Table 1Table 2

Differential diagnosis of unconjugated hyperbilirubinemiadetected after coronary artery stenting

Introduction. An increase in bilirubin and liver enzyme activity may be one of the side effects of statin therapy, often occurring in patients after AMI and coronary artery stenting, or in high and very high risk individuals on high and moderate intensity statin therapy. The frequency of occurrence of increased transaminases and bilirubin is according to different authors. Therefore, in terms of differential diagnosis, the cardiologist should consider Gilbert’s syndrome as a possible cause of hyperbilirubinemia. Description of the clinical case. The article considers a clinical case of differential diagnosis of non-conjugated hyperbilirubinemia detected in a patient after coronary artery stenting. The level of hemoglobin, erythrocytes, reticulocytes did not differ from normal values and did not change over time. This made it possible to exclude the hemolytic genesis of hyperbilirubinemia. Genetic testing was used to establish the homozygous form of Gilbert’s syndrome. However, the presence of fibrotic changes in the liver, an increase in not only unconjugated, but also conjugated bilirubin, hypertriglyceridemia, dyslipidemia, and stenosing atherosclerosis of the coronary arteries did not allow us to state that the patient had only Gilbert’s syndrome. Discussion. According to recent studies, this disease is characterized by a benign course and reduces the risk of developing cardiovascular diseases due to the antioxidant effect of bilirubin. In addition to Gilbert’s syndrome, the patient was diagnosed with an erased form of non-alcoholic fatty liver disease associated with metabolic syndrome. Conclusion. The disease was caused by insulin resistance, a high-calorie diet, excess consumption of saturated fats, refined carbohydrates, and a sedentary lifestyle. The drugs of choice in this case are statins, ezetemibe, and ursodeoxycholic acid. Their appointment allows not only to reduce cardiovascular risk, but also to slow down the further progression of liver fibrosis.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Risk factors for the development of diabetes among patients with low to moderate intensity statin therapy

Risk factors for the development of diabetes among patients with low to moderate intensity statin therapy

Moderate-intensity statin therapy. Efficacy and safety issues

High rates of cardiovascular (CV) morbidity and mortality dictates the need to determine approaches to therapy that would reduce complications rate and improve patient’s prognosis. High-intensity statin therapy is an integral part of the treatment of patients with high and very high cardiovascular risk. At the same time, there is a large cohort of patients who would benefit from moderate intensity statin therapy. In the present article we have summarized available data on hypolipidemic effects, pleiotropic effects and role of moderate intensity statin therapy, atorvastatin particularly, in reding the risk of major adverse cardiac events.

1228-P: Comparison between Combination of Low- or Moderate-Intensity Statin with Ezetimibe and High-Intensity Statin Monotherapy for Primary Prevention of Cardiovascular Disease and All-Cause Mortalities in Patients with Type 2 Diabetes—A Propensity-Matched Natio

Background and Aims: Here, we compared the effects of combination therapy of low- or moderate-statin with ezetimibe and high-intensity statin monotherapy in patients with type 2 diabetes without previous cardiovascular disease (CVD) on incident CVD and all cause mortalities in a real-world setting. Methods: Using the Korean National Health Insurance Service datasets, two cohorts comparing high intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination therapy were constructed using a 1:1 propensity score matching procedure and were followed up for 3.4 years. The primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause mortality. The secondary outcome was the occurrence of individual events. Results: Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy significantly reduced the risk of composite outcomes (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74 - 0.98, P=0.029) as well as stroke (HR 0.70, 95% CI 0.52 - 0.93, P=0.014), but not MI or all cause mortalities. However, there was no significant risk reduction in composite outcomes following low-intensity statin therapy with ezetimibe (HR 1.02, 95% CI 0.75 - 1.39, P=0.882) than that after high-intensity statin monotherapy. The statin with ezetimibe combination showed a consistent efficacy regardless of diverse patients’ baseline characteristics. Conclusions: Moderate-intensity statin with ezetimibe combination therapy was superior to high-intensity statin monotherapy for CVD primary prevention, and low-intensity statin with ezetimibe showed a comparable efficacy to high-intensity statin monotherapy in patients with type 2 diabetes. Disclosure Y.Hwang: None. S.Park: None. I.Jeong: None. K.Ahn: None. H.Chung: None.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Impact of High-Intensity Statin on Early Neurologic Deterioration in Patients with Single Small Subcortical Infarction.

One of the major hypotheses for early neurological deterioration (END) in single small subcortical infarction (SSSI) is the process of atherosclerosis. However, the association between statin therapy, especially high-intensity statin therapy, and its effectiveness in reducing the incidence of END during the acute phase of SSSI remains unclear. This study aimed to investigate the influence of high-intensity statin therapy compared to moderate-intensity statin therapy during the acute phase on the incidence of END in SSSI. The records of 492 patients with SSSI who received statin therapy within 72 h of symptom onset from a prospective stroke registry were analyzed. The association between END and statin intensity was evaluated using multivariable regression analysis for adjusted odds ratio (aOR). Of the 492 patients with SSSI (mean age: 67.2 years, median NIHSS score on admission: 3), END occurred in 102 (20.7%). Older age (aOR, 1.02; 95% confidence interval (CI), 1.00-1.05; p = 0.017), and branch atheromatous lesion (aOR, 3.49; 95% CI 2.16-5.74; p < 0.001) were associated with END. Early high-intensity statin therapy was associated with a lower incidence of END than moderate-intensity statin therapy (aOR, 0.44; 95% CI, 0.25-0.77; p = 0.004). In addition, there was significantly lower incidence of END in early administration (≤24 h) of high-intensity statin group. We identified an association between the intensity of early statin therapy and END in patients with SSSI. Early administration of high-intensity statin (≤24 h) is associated with a reduced incidence of END in patients with SSSI.

Abstract #1384613: Statin Utilization Among Patients with Type 2 Diabetes with and Without Cardiovascular Disease

Both American Diabetes Association (ADA) and American College of Cardiology (ACC) guidelines recommend that patients with diabetes between the ages of 40-75 years be prescribed at least a moderate-intensity statin. In all patients with diabetes who have established atherosclerotic cardiovascular disease (CVD), a high-intensity statin should be implemented as a secondary prevention measure. The purpose of this study was to assess the prescribing patterns of statin therapy in patients with type 2 diabetes (T2D) with and without established CVD in our large integrated delivery system. A retrospective cohort study was conducted using the enterprise-wide electronic health record (EHR) system at Cleveland Clinic to identify statin utilization among patients with T2D with and without CVD. A total of 74,949 patients were identified, 30,848 with established CVD, and 44,101 without. Among patients with and without established CVD, the mean age was 67 years and 62 years, 58% and 49% male, 73% and 72% white, 14% and 12% current smoker, median BMI 32 kg/m2 and 33 kg/m2, median eGFR 62 mL/min and 78 mL/min, and median A1c 6.9% and 6.9%, and median LDL 74 mg/dL and 84 mg/dL, respectively. Among patients with T2D without CVD, the rate of statin prescription at our institution was 60.4%, with 94% of those patients receiving at least a moderate-intensity statin (6.0% low-intensity, 59.1% moderate-intensity, 34.9% high-intensity). In patients with T2D and established CVD, the rate of statin prescription was 82.0%, with 59.3% receiving a high-intensity statin (3.7% low-intensity, 37% moderate-intensity). At our institution, only 60.4% of patients with T2D were prescribed statin therapy for primary prevention. However, among those, 94.0% were prescribed either a moderate- or high-intensity statin. While 82.0% of individuals with T2D and established CVD were prescribed a statin, only 59.3% were receiving high-intensity. These results have identified opportunities for improvement, including increasing the number of patients with T2D being prescribed at least moderate-intensity statin therapy for primary prevention, and ensuring that those being treated for secondary prevention are receiving high-intensity statin.

Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial

Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10mg with ezetimibe 10mg) or high-intensity statin monotherapy (rosuvastatin 20mg). The prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06-1.69; p=0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74-1.24; p=0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p<0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p=0.001). The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Hanmi Pharmaceutical, Seoul, South Korea.

Significance of Statin-Associated Muscle Symptoms and Its Impact on Patients Adherence and Outcomes.

Statin-associated muscle symptoms (SAMS) are one of the most common side effects of statins. This study aimed to explore the significance of SAMS among statin users by comparing statin users with a control group. To achieve our aims, a propensity score matching the retrospective cohort study was conducted in a single center tertiary hospital. The statin muscle symptoms were assessed using the Proposed Statin Myalgia Index Score, whereas the patient's adherence to medications was evaluated using the Morisky Medication Adherence Scale-8. We included 743 patients in our study; of them, 64.9% were on statin, whereas the rest were controls (35.1%). After propensity score matching, patients on statin had significantly higher rates of SAMS (5.0%) compared with control (1.6%) (AOR = 3.209; 95% CI: 1.020-10.091). However, there was no significant difference between statin users and controls in medications nonadherence ( P -value = 0.820). Our analysis among statins users revealed that moderate-intensity (2.671; 95% CI: 1.691-3.310) and high-intensity (3.552; 95% CI: 2.190-4.129) statin therapy was significantly associated with SAMS. In addition, autoimmune diseases were significantly associated with SAMS occurrence (AOR = 32.301; 95% CI: 1.785-584.374). Also, patients on PPIs had significantly less occurrence of SAMS (AOR = 0.145; 95% CI: 0.044-0.483), whereas patients on antiepileptic drugs had significantly higher SAMS occurrence (AOR = 72.337; 95% CI: 2.649-1975.201). Regarding MACE among statin users, there was no significant difference in the 1-year or 5-year MACE rate between statin users and controls. Our study suggests that SAMS are significant among statin users and must be addressed by health care providers to ensure that patients are still adherent to their medications and hence protected against cardiac events.

Underutilization of combination therapy in lipid lowering: a missed opportunity.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. LDL cholesterol (LDL-C) is the key driving force in the atherosclerotic process, and LDL-C lowering can change the trajectory of ASCVD and decrease cardiovascular (CV) events. In the light of new evidence, LDL-C goals have become more stringent in the ESC guidelines, especially for high-risk patients.1 Unfortunately, these goals are rarely reached in real life as shown in registries such as EUROASPIRE documenting a large implementation gap.2 The reasons for underimplementation are multiple, but underutilization of therapies is a major cause. Statins are the first line of treatment in lipid-lowering therapy (LLT) but may not get the patient to the guideline-recommended goals, and combination therapy may be necessary. The recent ESC guidelines recommend adding ezetimibe first, followed by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody inhibitors to the treatment regimen, since both agents have been documented to decrease CV events further on top of a statin.3 However, combination therapy with non-statin drugs is widely underutilized. A recent pan-European observational study (the DA VINCI study) reported that a majority of patients under both primary and secondary prevention were receiving moderate-intensity statin therapy. Only 28% were receiving high-intensity statins, 9% ezetimibe combination therapy, and 1% PCSK9 inhibitors.4 As a result, only a third of the patients achieved their LDL-C goal as recommended in the recent guidelines.