Moderate-intensity Statin Research Articles

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.

Efficacy, safety and clinical outcome associated with statin use for primary prevention in Korean patients with low-density lipoprotein cholesterol level ≥ 190 mg/dL: A retrospective cohort study.

Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL. A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity. Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408-1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823). Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL.

Trends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study.

Although statins are an effective strategy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population, the benefits for dialysis patients are controversial. We sought to assess trends of statin use and evaluate outcomes of statin therapy in dialysis patients with different types of ASCVD. This nationwide retrospective population-based cohort study using data from the Korean National Health Insurance Service included adult patients (aged ≥ 18 years) undergoing chronic dialysis who had an initial ASCVD event in the time period of 2013 to 2018. Annual trends of statin use according to age, sex, and ASCVD types were analyzed. The association between 1-year mortality and statin use was examined using multivariable Cox proportional hazards regression analyses. Among 17,242 subjects, 9,611(55.7%) patients were statin users. The overall prevalence of statin use increased from 52.9% in 2013 to 57.7% in 2018; the majority (77%) of dialysis patients were prescribed moderate-intensity statins. The proportions of low- or moderate-intensity statin use were similar, but high-intensity statin use increased from 5.7% in 2013 to 10.5% in 2018. The use of the statin/ezetimibe combination has gradually increased since 2016. Statin use was independently associated with the reduced 1-year all-cause mortality after adjusting for confounding factors (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.96, P = 0.004). The prevalence of statin prescriptions in dialysis patients after ASCVD event increased from 2013 to 2018. Most patients received moderate-intensity statin. However, high-intensity statin and statin/ezetimibe combination therapy has remarkably increased. Statin use was associated with decreased 1-year all-cause mortality in dialysis patients with ASCVD.

Is there benefit to adding ezetimibe to a statin for the secondary prevention of CVD?

YES. In patients with known cardiovascular disease (CVD), ezetimibe with a statin decreases major adverse cardiovascular events (MACE) but has no effect on all-cause and cardiovascular mortality, compared to a statin alone (strength of recommendation [SOR], A; meta-analysis of randomized controlled trials [RCTs] including 1 large RCT). In adults with atherosclerotic CVD (ASCVD), the combination of ezetimibe and a moderate-intensity statin (rosuvastatin 10 mg) was noninferior at decreasing cardiovascular death, major cardiovascular events, and nonfatal stroke, but was more tolerable, compared to a high-intensity statin (rosuvastatin 20 mg) alone (SOR, B; 1 RCT).

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.

Association between statin use and fractures among dialysis patients in the north of the West Bank in 2021

IntroductionHip fractures are associated with higher morbidity and mortality among dialysis patients than among the general population. Statins reduce the risk of hip and bone fractures. However, this protective effect has not been studied in dialysis patients. MethodsHemodialysis patients from hemodialysis centers located in the north of the West Bank were recruited (N ​= ​713) in a cross-sectional study in 2021. A statin user is a patient who has used statin for at least one year. The patient's medical records and an interview-administered structured questionnaire were used. Adjusted multiple logistic regression examined the association between statin use and fractures. A p-value less than 0.05 was considered statistically significant. ResultsThe final sample size was 529 patients, 184 were excluded, 60.7% were males, 54.4% were statin users, 76.1% were always adherent to their statin, and 75.3% used moderate-intensity statin. Statin users who were always adherent to their dose had a significantly lower risk of hip fractures (OR ​= ​0.090, p-value ​= ​0.026) than rarely adherent patients. In addition, patients who were always adherent with their statin dose (OR ​= ​0.188, p-value ​= ​0.007) or sometimes adherent (OR ​= ​0.171, p-value ​= ​0.022) had a significantly lower risk of having other bone fractures after dialysis than the rarely adherent counterparts. There were no differences between high and moderate-intensity statins regarding hip fracture effects (p-value >0.05). Moreover, the increased duration of dialysis significantly increased the risk of hip fractures (OR ​= ​1.349, p-value ​= ​0.003). ConclusionThe results of this study suggest that adherence to statin therapy was associated with decreased risk of hip fractures and other bone fractures among hemodialysis patients. These results could be the initial evidence of the protective effect against a vital health hazard among dialysis patients. This might ultimately contribute to re-considering the current statins prescription practice for dialysis patients. Further studies are recommended.

Effect of saroglitazar in South Indian patients with diabetic dyslipidemia uncontrolled on a moderate-intensity statin and the association of PPAR α and γ gene polymorphisms with its response

Background: Diabetic dyslipidemia is associated with atherosclerosis risk factors and cardiovascular disease. Saroglitazar is a dual PPAR α and γ agonist approved initially for diabetic dyslipidemia and later for managing non-alcoholic steatohepatitis and hyperglycemia in T2DM. This study was conducted to estimate the association of studied PPAR α and γ gene polymorphisms among patients with diabetic dyslipidemia at baseline and with triglyceride response to saroglitazar administration. Methods: A total of 54 diabetic dyslipidemia patients who are not controlled i.e., triglycerides (TG)&gt;200 mg/dl with moderate intensity of atorvastatin (≥10 mg) were recruited to the study. All the patients were given saroglitazar 4 mg once daily for 12 weeks. PPARα single nucleotide polymorphisms (SNPs) rs1800206, rs4253778, rs135542 and those of PPARγ gene rs3856806, rs10865710, rs1805192 were genotyped by real-time PCR. Results: 54 patients (67% female) with a mean age of 48.01±6.73 years were given saroglitazar 4 mg once daily for 12 weeks. There was a significant decrease in TG (36.9%) from baseline of 292.33±83.81mg/dl (mean±SD) to 184.46±95.90 mg/dl (&lt;0.001) and in HbA1c (0.66%) from baseline of 8.5% to 7.8% (&lt;0.001). PPAR α and PPAR γ gene variants did not show any association with TG lowering response. Conclusions: Saroglitazar 4mg once daily effectively decreases the TG, non-HDL-C levels, and HbA1c with no major adverse events, and TG lowering response is not associated with the studied polymorphisms.

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.

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

Statins utilization trends and expenditures in the U.S. before and after the implementation of the 2013 ACC/AHA guidelines

ImportanceStatins are drugs of choice in treating hyperlipidemia and preventing or reducing cardiovascular diseases. PurposeExplore statins utilization and expenditure trends in the United States before and after the publication of the 2013 ACC/AHA guidelines. MethodA retrospective, cross-sectional study of US noninstitutionalized civilians was conducted using MEPS data from 2008 to 2019. Adults who were ≥ 40 years old and who reported taking statins were included in the study. Primary outcomesStatins use patterns, total cost, and out-of-pocket spending in the general adults who reported taking statins medications. Expenditures were expressed in 2019 US dollars. ResultsIn this study, 409,804 individuals were eligible to be included (mean age [SE], 59 [0.1] years; 54% female). Of those participants, 22% reported taking statin therapy, and 11% of them filled only one statin prescription. The number of individuals in the general population who reported taking any statin climbed from 31 million (12%) in 2008–2009 to 92 million (35%) in 2018–2019, representing a 197% increase. After 2013, the number of individuals who used statins increased by 149%, from 37 million in 2012–2013 to 92 million users in 2018–2019. The annual number of statins prescriptions increased from 461 million to 818 million (77%; p = 0.000) between 2008 and 2019. Atorvastatin was the most prescribed medication in the statins class (36%), followed by simvastatin (34%). The moderate-intensity statins were the most used by the participants (60%). The total statins cost in 2013 was $8 billion and increased to $10 billion in 2019 (25%; p = 0.000). The total OOP expenditure trend sloped from $4.0 billion in the 2008–2009 cycle to $3.1 billion in 2018–2019. The average OOP paid by Asians was higher than that of other races at $141. ConclusionThe proportion of individuals who used statins significantly increased following the adoption of the 2013 ACC/AHA guidelines. The findings, however, demonstrated suboptimal prescribing trends of high-intensity statins, which need to be addressed by the stakeholders to maximize medication outcomes. Statins expenditures, especially the co-payments, significantly decreased. The results have shown that revised or new regulations have a substantial impact on the healthcare industry.

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.

Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis

BackgroundThe routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. ObjectivesWe evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). MethodsIn this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. ResultsAmong the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). ConclusionsModerate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665)

Grado de consecución de los objetivos lipídicos a largo plazo en una cohorte de pacientes con síndrome coronario agudo en práctica clínica real

Introduction and objectivesAccording to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. MethodsThis work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. ResultsA total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70mg/dl and 9.3% had LDL levels <55mg/dl. At the end of the follow-up (101 [88-111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved a LDL level <55mg/dl. ConclusionsAchievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7-10 years), especially in patients with recurrent ACS.

Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice

Introduction and objectivesAccording to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. MethodsThis work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. ResultsA total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88–111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. ConclusionsAchievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7–10 years), especially in patients with recurrent ACS.

Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study.

Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS. This prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up. Forty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment. Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease

In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. ClinicalTrials.gov Identifier: NCT02579499.

Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study.

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6months and ≥6months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Pragmatic and Early Usage of Statin in Patients with Diabetes for Prevention of Atherosclerotic Cardiovascular Disease

Background: An early initiation of statins in the diabetes population helps in prevention of atherosclerotic cardiovascular disease (ASCVD). However, there is a paucity of data on its use in young Indian patients with diabetes. This survey report aimed to provide opinion-based recommendations for pragmatic usage of statin in diabetes population of India. Material and Methods: Discussion and virtual survey (a questionnaire of 18 questions) was conducted at 16 round table meetings (RTMs) which included participation of health-care practitioners (HCPs) from India. On the basis of their opinions and discussion, general recommendations about early usage of statins in diabetes for prevention of ASCVD were derived. Results: Out of 261 HCPs participated, 56.1% recommended initiating statins in patients aged 41–50 years irrespective of their total/low-density lipoprotein cholesterol (LDL-C) levels. Among people with diabetes aged between 20 and 39 years, 38.9% of HCPs considered LDL-C &gt;100 mg/dL and 77% of HCPs considered history of ASCVD as a risk factor for early statin initiation. Overall, 98.9% of HCPs agreed that early initiation of statin in people with diabetes and ASCVD risk factors will help reduce ASCVD. The majority of HCPs recommended initiating moderate-intensity (51.2%) and low-intensity (43.8%) statins and assess every 3 months for tolerance and compliance in people with diabetes (aged 20–39 years) and additional ASCVD risk factors. The use of rosuvastatin (78.5% of HCPs) was preferred for early initiation in people with diabetes. Majority of HCPs agreed (57.3%) or strongly agreed (36.2%) that rosuvastatin has more clinical utility compared to other statins due to better LDL-C-lowering effect and other pleiotropic effects. Physician's inertia limits the effective use of statins among young adults with diabetes (55.8%), and 65.8% of HCPs recommended screening of people with diabetes for additional ASCVD risk factors. Conclusion: The participating HCPs opined that early initiation of statin therapy in people with diabetes and ASCVD risk factors will help reduce ASCVD. Rosuvastatin is mostly recommended for early initiation of statin therapy among the diabetes population for prevention of ASCVD. There is a necessity of using a proactive approach to screen for additional ASCVD risk factors in young individuals with diabetes and further increase the awareness about benefits of initiating statin therapy from an early stage.

1075 USE OF LIPID-LOWERING COMBINATION THERAPIES IN SANTORINI STUDY: EVIDENCE FROM ITALIAN COHORT

Abstract The SANTORINI registry is an observational study that aims to evaluate the management of patients with high and very high cardiovascular (CV) risk in clinical practice, collecting data at enrolment and after 12 months. Italy participated in this study with 1531 patients at very high risk and 446 at high risk. The scope of the present analysis was to investigate low-density lipoprotein cholesterol (LDL-C) goal attainment in patients who do not qualify for PCSK9 inhibitors (PCSK9i) (according to Italian reimbursement regulations) in Italian cohort, with focus on patients in secondary prevention. The current indications for PCKS9i charged to the National Health System in Italy in secondary prevention, are for patients aged ≤ 80 years with LDL-c levels ≥ 70 mg/dl in at least three detections despite therapy for at least 6 months with high intensity statin at the highest tolerated dose and ezetimibe or after a single LDL-C detection for recent myocardial infarction or multiple cardiovascular events or with demonstrated intolerance to statins and/or ezetimibe. At enrolment, a total of 509 (33.2%) of 1531 patients at very-high risk had an LDL-C level of less than 70 mg/dl. Of them, about half do not reach the LDL-C target. In particular, 34.4% takes statin monotherapy, and 50.3% of them do not reach the target. Even patients taking high-intensity statins as monotherapy reach the target in only 47.9% of cases, leaving more than half of patients with LDL-C levels between 55 and 70 mg/dl. Regarding combination therapy, statin and ezetimibe, patients taking this combination account for 26.9%, of these those taking the combination of moderate-intensity statin and ezetimibe reach the target in 56.7% of cases while those taking high-intensity statins and ezetimibe reach the target in 51.4% of cases. Our findings show that there is a proportion of patients with LDL-C below 70 mg/dl who do not qualify for PCSK9i who are not at target for LDL-C levels despite maximal therapy with statins and ezetimibe.