Intensive Statin Research Articles

The predictive significance of ratio between white blood cells count and serum albumin in assessing the functional outcome of acute ischemic stroke

Introduction: The acute ischemic infarction is associated with significant damage to brain parenchyma, where the high degree of acute inflammation is found. This work aimed to study the predictive value of ratio between blood WBCs and serum albumin levels in assessing the functional outcome in subjects with acute ischemic stroke. Materials and methods: A prospective observational study was conducted on 223 subjects from February 2022 to August 2022 at K.R. Hospital, Mysore. The data collected from patients of acute ischemic stroke, with the onset of stroke within 24 hours. Severity of stroke was assessed by using National Institute of Health Stroke Scale (NIHSS) at the time of admission. Data was collected using a pretested proforma meeting the objectives of the study. Results: The study has 124(55.6%) male and 99(44.4%) of female patients. Most of the patients (65%) were in the age group of more than 66 years. Most of the patients i.e., 66 (29.6%) had moderate to severe stroke at presentation as assessed by NIHSS stroke scale. At the end of third month of follow up, the acute ischemic stroke patients with MRS of >3 had WBCs count/serum albumin ratio of 4361.1 (p value - 0.001). Conclusion: The significant acute inflammation is found in acute ischemic stroke and it may be one of the causes of poor outcome and disability in so many ischemic stroke patients. This study once again endorses the use of high intensive statins and adequate dose of antiplatelet agents as early as possible in acute ischemic stroke patients. Keywords: acute ischemic stroke; WBCs; Modified Rankin Scale; NIHSS; serum albumin

The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study.

Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries. This is a sub-study of a prospective observational study under the title of "Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study." Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients' cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry. A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta -0.21, 95% confidence interval -0.36 to -0.07, p = 0.005). Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02458755.

Value of the clinical pharmacist interventions in the application of the American College of Cardiology (ACC/AHA) 2018 guideline for cholesterol management.

The study aims to examine the extent to which the updated ACC/AHA management of blood cholesterol guideline (2018) is implemented in practice and to assess the value of the clinical pharmacist interventions in improving physicians' adherence the guidelines recommendations. We utilized in this study an interventional before-after design. The study was conducted on 272 adult patients who visited the study site internal medicine clinics and were candidates for statin therapy based on the 2018 ACC/AHA guidelines for cholesterol management. Adherence to guideline recommendations was measured before and after clinical pharmacists' interventions by calculating the percentage of patients receiving statin therapy as per guideline recommendation, the type and intensity (moderate or high intensity) of statin therapy used, and the need for additional non-statin therapy. Adherence with guideline recommendations was significantly improved from 60.3% to 92.6% (X2 = 79.1, p = 0.0001) after clinical pharmacist interventions. Among patients who were on statin therapy, the percentage of those who were on proper statin intensity increased significantly from 47.6% to 94.4% (X2 = 72.5, p = 0.0001). The combination of statins with non-statin therapies such as ezetimibe and PCSK9 inhibitors increased from 8.5% to 30.6% (X2 = 95, p<0.0001) and from 0.0% to 1.6% (X2 = 6, p = 0.014), respectively. The use of other lipid-lowering agents was diminished from 14.6% to 3.2% (X2 = 19.2, p<0.0001). Collaboration between physicians and clinical pharmacists is a crucial strategy to improve patients' treatment and hence, achieve better health outcomes among patients suffering from dyslipidemia.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial

BackgroundCurrent guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. Trial designThis investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. ConclusionsThe SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Disparate statin prescribing following hospital discharge for stroke or transient ischemic attack: Findings from COMPASS.

Published guidelines recommend high-intensity statins following an ischemic stroke or transient ischemic attack (TIA). The authors examined the potential for disparate patterns of statin prescribing in a cluster randomized trial of transitional care following acute stroke or TIA. Medications taken before hospitalization and statins prescribed at discharge among stroke and TIA patients at 27 participating hospitals were examined. Any statin and intensive statin prescribed at discharge were compared by age (<65, 65-75, >75 years), racial category (White vs. Black), sex (male vs. female), and rurality (urban vs. non-urban) using logistic mixed models. Among 3211 patients (mean age 67 years; 47% female; 29% Black), 90% and 55%, respectively, were prescribed any statin or intensive statin therapy at discharge. White (vs. Black) patients (0.71, 0.51-0.98) less commonly received any statin prescription, while stroke (vs. TIA) patients (1.90, 1.38-2.62) and those residing in urban areas (1.66, 1.07-2.55) more commonly received any statin prescription. Among those prescribed a statin, only 42% of White and 51% of Black patients >75 years. were prescribed an intensive statin; the OR for intensive statin prescribing was 0.44 for patients >75 years and was similar in a subgroup not on a statin previously. Following stroke or TIA, statin prescribing remains lower in White patients, in those with TIA, and in those in non-urban areas. Intensive statin prescribing remains limited, particularly in patients >75 years. These data may inform efforts to improve guideline concordant prescribing for post-stroke patients.

ASSESSMENT OF DRUG UTILIZATION PATTERN OF STATIN THERAPY FOR PRIMARY PREVENTION OF CARDIOVASCULAR RISK IN DIABETIC PATIENTS ATTENDING TERTIARY CARE TEACHING HOSPITAL OF CENTRAL INDIA

Background: Diabetes Mellitus is one of the prevalent metabolic disease which is associate with dyslipidemia. This poses this patient for signicantly increased cardiovascular risk events like stroke, myocardial infarction etc. Statins are widely used among these patients for primary prevention of cardiovascular risk. This study emphasizes on pattern of statin therapy being practiced in Indian setup and lacunae related to with aspect of improving public health Methods: This study was a crossectional observational study conducted in a tertiary care teaching hospital of central India. The study was started after obtaining clearance from Institute Ethics Committee. The patients satisfying the inclusion criteria were recruited in this study after obtaining Informed consent. The diabetic patients were assessed for statin therapy and intensity of statin therapy widely prescribed and practiced with respect to Indian population. Results: Of total 2680 diabetic patients recruited in this study, 1800 (67.16%) were prescribed with statin therapy, of which 41.5% were males and 25.66% were females. 1280 diabetic patients were prescribed with Atorvastatin and 520 were prescribed with Rosuvastatin.Of all the available statins, Two statins, Atorvastatin and Rosuvastatin, was prescribed to the diabetic patients the most. Conclusion: This study will be providing baseline data regarding drug utilization pattern of statins in diabetic patients. This study will help in assessing the statin eligibility and to determine data pertaining to overuse or underuse of statins in diabetic patients. It also emphasizes the pattern of statin being prescribed based on its intensity. The data of this study will be useful to plan further research related cardiovascular risk and statin considering various factors for Indian population

Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials

Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of risk for major adverse cardiovascular events, cardiovascular death, and all-cause-death among patients receiving statins. We did a collaborative analysis of patients with-or at high risk of-atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and of increasing baseline LDLC (a biomarker of residual cholesterol risk) were assessed as predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death. Hazard ratios (HRs) for cardiovascular events and deaths were calculated across quartiles of high-sensitivity CRP and LDLC in analyses adjusted for age, gender, BMI, smoking status, blood pressure, previous history of cardiovascular disease, and randomised treatment group assignment. 31 245 patients were included in the analysis from the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13 078) trials. The observed ranges for baseline high-sensitivity CRP and LDLC, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile vs lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20-1·43; p<0·0001), cardiovascular mortality (2·68, 2·22-3·23; p<0·0001), and all-cause mortality (2·42, 2·12-2·77; p<0·0001). By contrast, the relationship of residual cholesterol risk was neutral for major adverse cardiovascular events (highest LDLC quartile vs lowest LDLC quartile, adjusted HR 1·07, 95% CI 0·98-1·17; p=0·11), and of low magnitude for cardiovascular death (1·27, 1·07-1·50; p=0·0086) and all-cause death (1·16, 1·03-1·32; p=0·025). Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC. These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that combined use of aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk. Kowa Research Institute, Amarin, AstraZeneca.

Abstract P448: Trends and Predictors of Statin Initiation Among Veterans With Familial Hypercholesterolemia

Introduction: Familial hypercholesterolemia (FH), defined as LDL-C ≥190mg/dL, is a strong cardiovascular disease (CVD) risk factor. The AHA/ACC guidelines recommend high intensity statins for primary prevention irrespective of global risk assessment. We sought to characterize trends and predictors of statin initiation among Veterans with FH in the Veterans Health Administration (VHA). Methods: Inclusion criteria consisted of care at the VHA (2002-2014), age ≥21 years, baseline LDL-C ≥190 mg/dL, no prevalent CVD, no prior statin use, and statin initiation within 90 days of LDL-C measurement. We defined baseline LDL-C in quartiles: Q1=190-195, Q2=196-202, Q3=203-215, and Q4 &gt;215 (mg/dL). Statin intensity was defined as average intensity over one year following baseline LDL-C measurement. Multivariable logistic regression models were constructed to determine the odds of any statin initiation and high intensity statin initiation. Results: Over 12 years, 165,110 Veterans (age=52.9±11.9, men=91%; white race=74%) were included. Statins were initiated in 88,878 patients (overall 54%, 62% in 2014). Overall, 29,533 Veterans were on high intensity statins (overall 33%, 20% in 2002, 50% in 2014). In multivariable-adjusted logistic regression models, significant predictors of statin initiation were age, white race, diabetes hypertension, smoking, baseline LDL-C, and recent calendar year. Among those initiated on high intensity statins, the same predictors were significant; however, African Americans were more likely to be started on a high intensity statin (Table). Conclusions: Among Veterans with FH, the odds of statin initiation are higher among older, Caucasian, hypertensive, diabetic, and smoking veterans. The odds of statin prescription have increased over time with a higher proportion receiving high intensity statins more recently. These data reflect the VHA changes in clinical practice concordant with ACC/AHA guidelines.

Abstract P432: Statin Initiation for Primary Prevention and Dose Intensity According to Age in the Women’s Health Initiative

Introduction: Over 50% of US adults older than 75 live free of atherosclerotic cardiovascular disease (ASCVD) and diabetes (DM), yet data on incident statin use among this population are lacking. Our objective was to assess statin initiation by age among the Women’s Health Initiative cohort free of ASCVD and DM at baseline (1993). Hypothesis: Statin initiation is higher at older ages and differs by race/ethnicity. Methods: Exclusions were statin use at baseline, known ASCVD, DM, and no follow-up after baseline. Self-reported medication use was assessed in 1996 and 2008. Specific statin and dose prescribed at the time of initiation were identified using National Drug Codes and determined statin intensity, defined by the ACC/AHA guidelines. We estimated the adjusted association between age group (&lt;65, 65-74, and ≥75) and statin initiation and assessed for heterogeneity by race/ethnicity. We also assessed statin dose at the time of initiation. Results: Over 12 years of follow-up, 27% of 99,631 women free of ASCVD and DM at baseline initiated a statin; initiation was lower with older age (Table). This association remained after adjustment for ASCVD risk factors and did not differ by race/ethnicity (p for interaction &gt;0.5). Moderate intensity dose was most common at statin initiation overall, and moderate and high intensity dose were both lower with older age. Conclusion: Of women free of ASCVD and DM, women older than 75 were least likely to start a statin and most likely to start low intensity statin therapy at initiation than younger women. We identified a potential clinical gap for investigation: whether lower overall use of statins and lower intensity statin therapy among older women are associated with preventable ASCVD.

Abstract 60: Impact of a Multisite, Protocol-Driven, Nurse Practitioner-Led, Cardiovascular Prevention Program in a Hispanic Medicare Advantage Population at High Risk for ASCVD: Healthy Heart Program at Cano Health.

Introduction: Despite availability of effective and inexpensive pharmacologic therapies for hypercholesterolemia and hypertension, many patients at high risk for atherosclerotic cardiovascular disease (ASCVD) do not achieve optimal low-density lipoprotein (LDL) and systolic blood pressure (SBP) levels. We hypothesized that risk factor control could be improved by using nurse practitioners and a guideline-directed protocol in a Medicare Advantage (MA) population. Methods: We designed and implemented an ongoing 18 site, multistate (FL, TX, NV), ASCVD risk assessment and management program (Healthy Heart) in a large national MA primary care clinic (Cano Health). The cardiometabolic risk assessment and management program was designed by a team of preventive cardiologists, with the plan of being Nurse Practitioner (NP)-led, with remote support by a cardiologist. Protocols provided details on initiation and titration of drug therapy to achieve LDL-C and SBP goals. Patients with organ transplants, advanced cancer, an ejection fraction &lt;35%, and on hemodialysis were excluded. Results: From October 2021-October 2022, 5430 patients were enrolled in the program. A total of 1858 (34.2%) had established ASCVD, 1033 (19.0%) had diabetes mellitus (DM). A total of 713 (13.1%) had both ASCVD and DM. In patients who had ASCVD and diabetes together, high intensity statin use increased from 39.4% to 68.3% after enrollment; 52.66% achieved an LDL-C &lt;70 mg/dl after enrollment compared to 31.0% at baseline. Antihypertensive medications were intensified in 408/1041 (39.2%) of ASCVD and 276/558 (49.5%) of DM patients, with a higher proportion achieving a SBP &lt;130 mm Hg after enrollment. Conclusions: Implementing a novel cardiovascular prevention program in a population of mostly Hispanic MA patients at high risk for ASCVD, using NPs, with strict adherence to a step-by-step evidence-based protocol supervised by cardiologists, is associated with reduction in LDL levels and SBP and with improvement in reaching LDL and SBP targets.

Abstract P628: The Right Dose for the Right Patient - High Intensity Rosuvastatin Dosing in Patients With Chronic Kidney Disease

Introduction: The utilization of high intensity statins for lipid lowering therapy has revolutionized our approach to decreasing the incidence of myocardial infarction. In February 2003, rosuvastatin was approved by the FDA for use at dosages ranging from 5mg to 40mg daily, with lower doses recommended for patients with reduced glomerular filtration rates (GFRs). Prescribing patterns of rosuvastatin for patients with chronic kidney disease (CKD), notably those with a GFR &lt; 30 mL/min/1.73m 2 , is largely unstudied. Methods: A single center retrospective study of all admitted patients with a chart diagnosis of chronic kidney disease (CKD) over the course of one year was performed. Data on inpatient rosuvastatin orders and overall statin selection was collected and analyzed. Results: Between 10/1/2021-10/1/2022, a total of 5359 patients were admitted with the diagnosis of CKD. In this cohort, 62% (n = 3325) had a prescription for a statin placed for continuation of outpatient care or new initiation of lipid lowering therapy. Most patients were on atorvastatin (69.4%, n = 2310) or rosuvastatin (20.9%, n = 695). Among inpatients with CKD, a total of 1465 inpatient rosuvastatin orders were placed. Almost 32% (n = 468) of these patients had an eGFR &lt;30 mL/min/1.73m 2 . Of this cohort, 48% (n = 223) were prescribed doses of 20mg or 40mg rosuvastatin daily, which is above the FDA recommended dose for this population ( Figure 1 ). Conclusions: A large percentage of patients on lipid lowering therapies have CKD, and data regarding renal outcomes associated with high doses of statins in this population are limited. In this large single center study, we found that nearly half of patients with eGFR &lt;30 mL/min/1.73m 2 were on inappropriately high doses of rosuvastatin when considering their kidney function. Further research into long term outcomes and rosuvastatin dosing in this patient population is needed.

Secondary prevention and follow-up of patients with ACS and not-at-target LDL: An Italian real-world retro-prospective analysis by the INERTIA group

BackgroundIn patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. ObjectiveReport a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. MethodsRetrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. ResultsData from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C <55 mg/dL according to ESC 2019 guidelines. Fifty percent of patients achieved the <55 mg/dL target for LDL-C after a mean of 120 days from the ACS event. ConclusionsOur analysis, though numerically and methodologically limited, suggests that management of cholesterolaemia and achievement of LDL-C targets are largely suboptimal and need significant improvement to comply with the lipid-lowering guidelines for very high CV risk patients. Earlier high intensity statin combination therapy should be encouraged in patients with high residual risk.

A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol.

Low serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs. The Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs. This is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China. CHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up. The primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice. Clinicaltrials.gov, identifier: NCT05589454.

Impact of pre-lung transplant statin use on the development of primary graft dysfunction.

Primary graft dysfunction (PGD) is a common occurrence following lung transplantation and contributes to short- and long-term morbidity and mortality. Current management strategies are limited, and robust data to support their use is lacking. Preventative strategies attenuating the recipient's inflammatory state suggest statin therapy may decrease the incidence and severity of PGD. This study aims to evaluate the impact of pre-transplant statin use on the incidence and severity of PGD following lung transplantation. A retrospective cohort study was performed evaluating all patients undergoing bilateral lung transplantation from September 2012 to December 2019. The primary outcome was the incidence of PGD by grade, defined as the highest grade of PGD experienced in the first 72h. Secondary outcomes included length of intensive care unit and hospital stays and mortality. Of the 357 patients included in the study, 107 received statin therapy prior to transplant (statin group) and 250 did not (no statin group). PGD occurred in 257 (72%) patients; in the entire cohort, 99 (28%) patients experienced PGD grade 1, 59 (17%) grade 2, and 99 (28%) grade 3. A significantly lower incidence of PGD was observed in the statin group (64.5% vs 75.2%, p= 0.039); however, the association did not remain significant on multinominal analysis for an overall incidence of any PGD (p= 0.275) or incidence of severe PGD (p= 0.240). Statin intensity was not associated with the development of PGD. Pre-transplant statin therapy did not appear to impact the development of PGD following lung transplantation. Future prospective studies should further evaluate the impact of statin intensity and duration on the incidence and severity of PGD.

Abstract TP196: Real Life Utility Of PCSK9 Inhibitors Following Ischemic Stroke

Introduction: Hyperlipidemia is a modifiable risk factor for stroke, with the magnitude of LDL-C reduction correlating to risk of recurrent ischemic stroke. A high-intensity statin is considered standard of care in addition to dietary modification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are used if the LDL-C target is not achieved despite maximally tolerated statins with ezetimibe. We investigated the role for PCSK9 inhibitors in our ischemic stroke population. Methods: An IRB approved retrospective review of patients admitted for acute ischemic stroke between 2019 – 2020 was performed. We estimated the probability of benefit from PCSK9 treatment with the following criteria: LDL &gt; 190 regardless of treatment, LDL 161-190 on any dose statin therapy, and LDL 131-160 on high intensity statin therapy. Results: 774 patients with ischemic stroke were admitted during this time frame. Mean age 62.8 +/- 13.2 with 57% male (52% Black, 42% White). 584 (75%) of these patients had LDL above goal. One patient was on PCSK9 therapy on admission. Although the majority of our patients had uncontrolled cholesterol, only one additional patient would meet the strict prescription criteria for PCSK9 therapy of being adherent to maximal tolerated statin dose and ezetimibe with LDL above goal. Other potential patients with estimated benefit include LDL &gt;190 (20 patients), LDL 161-190 (16 patients), LDL 131-160 (13 patients). In total this amounts to 6.7% of stroke patients who we would expect to need PCSK9 inhibitors in the future. Conclusion: Using conservative projections, we estimate that about 1 in 14 patients with ischemic stroke could benefit from PCSK9 therapy. Achieving LDL targets more consistently is a promising approach to decreasing the recurrent stroke rate. Further prospective data evaluating outcomes after initiating PCSK9 inhibitor treatment are needed to validate these findings.

Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function.

Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low-moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 , 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group ( P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

Abstract 138: Hypoperfusion Delay Volume Predicts Early Stroke Recurrence Risk In Symptomatic Anterior Circulation Intracranial Atherosclerotic Disease

Introduction: Data on predictors of early stroke recurrence in patients with symptomatic intracranial atherosclerotic disease (sICAD) is limited. We hypothesized that hypoperfusion delay predicts stroke recurrence within 90-days. Methods: We retrospectively collected all patients hospitalized with anterior circulation sICAD over 3 years (April 2019-April 2022) at a comprehensive stroke center. We collected demographics, clinical risk factors, radiological variables, and treatment strategies. Patients with an indication for anticoagulation such as atrial fibrillation and those with intracranial stenting or angioplasty were excluded. The outcome (verified by two independent reviewers) was recurrent stroke within 90 days in the affected artery. We assessed factors associated with stroke recurrence. We measured the effect of hypoperfusion delay volume on stroke recurrence using Cox-regression models. Results: Out of 131 sICAD hospitalizations during the study period, 66 involved the middle cerebral artery (MCA) M1 segment or intracranial internal carotid artery (ICA) and 44 patients met the inclusion criteria. The mean age was 71 years and 41% were women; 75% were treated with best medical management (dual antiplatelet therapy/high intensity statin therapy); and 75% had baseline perfusion imaging performed. Over 90 days, 11/44 (25%) patients had recurrent stroke. Factors associated with recurrence stroke were no best medical management (15.2% vs. 54.5%, p = 0.02), hypoperfusion Tmax&gt;4 sec mismatch volume (p = 0.003), and hypoperfusion delay Tmax&gt;6 sec mismatch volume (p=0.01). Using Youden’s cutoff for Tmax&gt;4 sec mismatch (13 mL) and for Tmax&gt;6 sec mismatch (5 mL), the risk of recurrent stroke at 90 days in separate models was higher in patients with Tmax&gt;4 sec delay mismatch volume &gt; 13 mL (HR 11.98 95% CI 1.48-96.96 p=0.02) and Tmax&gt;6 sec mismatch volume &gt; 5 mL (HR 4.37 95% CI 1.02-18.82, p=0.048). Effect size of the associations did not meaningfully change after adjusting for best medical management. Conclusion: Hypoperfusion delay is associated with an increased recurrent stroke risk within 90 days in patients with sICAD, despite best medical management. Validation by large prospective studies is warranted.

Rationale and design of a randomised double-blind 2×2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis (INSPIRES)

BackgroundIt remains unclear if intensive antiplatelet and statin treatments begun within 24–72 hours of cerebral ischaemic events from intracranial or extracranial atherosclerosis is effective or safe.MethodsThe Intensive Statin and Antiplatelet...

High- vs. Low-Intensity Statin Therapy and Changes in Coronary Artery Calcification Density after One Year.

Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: -45.8 ± 38.5 vs. -72.9 ± 46.0 mg/dL, p &lt; 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p &lt; 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (&lt;median: 2.0 ± 24.3 HU, ≥median: 3.6 ± 21.9 HU, p = 0.34), Agatston score at baseline (&lt;100: 2.6 ± 22.5 HU vs. 3.2 ± 25.6 HU, p = 0.82; ≥100: 4.8 ± 17.0 HU vs. 3.8 ± 16.6 HU, p = 0.44, for HIST vs. LIST; respectively), and equal number of lesions in both CT scans (3.7 ± 20.3 HU vs. 7.0 ± 22.2 HU, p = 0.24) showed similar results. HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up.

Intracranial plaque with large lipid core is associated with embolic stroke of undetermined source.

To investigate an association between percentage lipid-rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. A total of 167 ESUS patients with 259 non-stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi-dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high-resolution magnetic resonance imaging. We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854-3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835-3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056-0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction=0.001). This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future.