Statin Therapy For Primary Prevention Research Articles

Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations

In 2023, the American Heart Association (AHA) developed the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations to estimate 10-year risk of atherosclerotic cardiovascular disease (ASCVD), as an update to the 2013 pooled cohort equations (PCEs). The PREVENT equations were derived from contemporary cohorts and removed race and added variables for kidney function and statin use. To compare national estimates of 10-year ASCVD risk using the PCEs and PREVENT equations and how these equations affect recommendations for primary prevention statin therapy. This cross-sectional study included adults aged 40 to 75 years who participated in the National Health and Nutrition Examination Survey from 2017 to March 2020. Adults were defined as eligible for primary prevention statin use based on the 2019 AHA/American College of Cardiology guideline on the primary prevention of cardiovascular disease. Data were weighted to be nationally representative and were analyzed from December 27, 2023, to January 31, 2024. The 10-year ASCVD risk and eligibility for primary prevention statin therapy based on PREVENT and PCE calculations. In the weighted sample of 3785 US adults (mean [SD] age, 55.7 [9.7] years; 52.5% women) without known ASCVD, 20.7% reported current statin use. The mean estimated 10-year ASCVD risk was 8.0% (95% CI, 7.6%-8.4%) using the PCEs and 4.3% (95% CI, 4.1%-4.5%) using the PREVENT equations. Across all age, sex, and racial subgroups, compared with the PCEs, the mean estimated 10-year ASCVD risk was lower using the PREVENT equations, with the largest difference for Black adults (10.9% [95% CI, 10.1%-11.7%] vs 5.1% [95% CI 4.7%-5.4%]) and individuals aged 70 to 75 years (22.8% [95% CI, 21.6%-24.1%] vs 10.2% [95% CI, 9.6%-10.8%]). The use of the PREVENT equations instead of the PCEs could reduce the number of adults meeting criteria for primary prevention statin therapy from 45.4 million (95% CI, 40.3 million-50.4 million) to 28.3 million (95% CI, 25.2 million-31.4 million). In other words, 17.3 million (95% CI, 14.8 million-19.7 million) adults recommended statins based on the PCEs would no longer be recommended statins based on PREVENT equations, including 4.1 million (95% CI, 2.8 million-5.5 million) adults currently taking statins. Based on the PREVENT equations, 44.1% (95% CI, 38.6%-49.5%) of adults eligible for primary prevention statin therapy reported currently taking statins, equating to 15.8 million (95% CI, 13.4 million-18.2 million) individuals eligible for primary prevention statins who reported not taking statins. This cross-sectional study found that use of the PREVENT equations was associated with fewer US adults being eligible for primary prevention statin therapy; however, the majority of adults eligible for receiving such therapy based on PREVENT equations did not report statin use.

Summary for Patients: Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults.

Summary for Patients: Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults.

Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults : Real-World Evidence From a Target Trial Emulation Study.

There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials. To investigate the benefits and risks of using statins for primary prevention in old (aged 75 to 84 years) and very old (aged ≥85 years) adults. Sequential target trial emulation comparing matched cohorts initiating versus not initiating statin therapy. Territory-wide public electronic medical records in Hong Kong. Persons aged 75 years or older who met indications for statin initiation from January 2008 to December 2015 were included. Participants with preexisting diagnosed CVDs at baseline, such as coronary heart disease (CHD), were excluded from the analysis. Among 69 981 eligible persons aged 75 to 84 years and 14 555 persons aged 85 years or older, 41 884 and 9457 had history of CHD equivalents (for example, diabetes) in the respective age groups. Initiation of statin therapy. Incidence of major CVDs (stroke, myocardial infarction, or heart failure), all-cause mortality, and major adverse events (myopathies and liver dysfunction). Of 42 680 matched person-trials aged 75 to 84 years and 5390 matched person-trials aged 85 years or older (average follow-up, 5.3 years), 9676 and 1600 of them developed CVDs in each age group, respectively. Risk reduction for overall CVD incidence was found for initiating statin therapy in adults aged 75 to 84 years (5-year standardized risk reduction, 1.20% [95% CI, 0.57% to 1.82%] in the intention-to-treat [ITT] analysis; 5.00% [CI, 1.11% to 8.89%] in the per protocol [PP] analysis) and in those aged 85 years or older (ITT: 4.44% [CI, 1.40% to 7.48%]; PP: 12.50% [CI, 4.33% to 20.66%]). No significantly increased risks for myopathies and liver dysfunction were found in both age groups. Unmeasured confounders, such as lifestyle factors of diet and physical activity, may exist. Reduction for CVDs after statin therapy were seen in patients aged 75 years or older without increasing risks for severe adverse effects. Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older. Health Bureau, the Government of Hong Kong Special Administrative Region, China, and National Natural Science Foundation of China.

Abstract P510: Trends in Statin Therapy for Primary Prevention Among Older Veterans, 2003-2020

Introduction: The burden and risk of atherosclerotic cardiovascular disease (ASCVD) in US Veterans is higher than the general population, yet rates of use of medications for primary prevention, specifically statins, are not well described. Since the early 2000s, trial data have proven the efficacy of statins for primary prevention, further encouraged by updated guidelines (notably 2001, 2013, 2018). Therefore, we sought to examine the proportion of older veterans free of ASCVD and trends of statin use for primary prevention within this cohort from 2003 to 2020. Methods: Study participants comprised all US Veterans ≥65 years, free of ASCVD, and with at least one visit in the Veteran’s Health Administration (VHA) in the year prior. Statin users had at least two or more prescriptions of any statin in each one-year period studied. VA prescription data were linked to Medicare/Medicaid to ensure complete capture of statin use. Descriptive statistics and crude proportions were calculated by year of study entry. Results: From 2003-2020, there were 5.1 million Veterans aged 65 and older who received regular care in VHA. The overall proportion of veterans free of ASCVD in that period was 60% (N=3,159,705). Statin prescriptions for primary prevention have increased from 39% in 2003 to 52% in 2020, remaining steady after 2007. For example, in 2011, 51% were prescribed statins, mean age 73±7, 87% white, 98% male, 82% hypertension, 37% diabetes, 94% hyperlipidemia; while in 2017, 53% were prescribed statins (age 72± 7, 80% white, 97% male, 73% hypertension, 31% diabetes, 74% hyperlipidemia), received statin therapy for primary prevention (Figure). Conclusion: A substantial proportion of Veterans ≥65 years were at risk for ASCVD. While statin prescriptions for primary prevention have increased from 2003-2020, over the past 15 years, they have remained at around 50%. These findings indicate a focus on primary prevention among older Veterans is needed.

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

Use of coronary artery calcium score and coronary CT angiography to guide cardiovascular prevention and treatment.

Currently, cardiovascular risk stratification to guide preventive therapy relies on clinical scores based on cardiovascular risk factors. However, the discriminative power of these scores is relatively modest. The use of coronary artery calcium score (CACS) and coronary CT angiography (CCTA) has surfaced as methods for enhancing the estimation of risk and potentially providing insights for personalized treatment in individual patients. CACS improves overall cardiovascular risk prediction and may be used to improve the yield of statin therapy in primary prevention, and possibly identify patients with a favorable risk/benefit relationship for antiplatelet therapies. CCTA holds promise to guide anti-atherosclerotic therapies and to monitor individual response to these treatments by assessing individual plaque features, quantifying total plaque volume and composition, and assessing peri-coronary adipose tissue. In this review, we aim to summarize current evidence regarding the use of CACS and CCTA for guiding lipid-lowering and antiplatelet therapy and discuss the possibility of using plaque burden and plaque phenotyping to monitor response to anti-atherosclerotic therapies.

Identification of subgroups within a Japanese older adult population for whom statin therapy is effective in reducing mortality.

Use of statins for primary prevention can reduce all-cause mortality in Asian elderly populations, but their effect and the specific effective subgroups in the elderly Japanese population remain unclear. This study examined the relationship between statin therapy for primary prevention and mortality reduction in older Japanese adults, and investigated the effective subgroups. The cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33-0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group compared with that in the control group was 0.05 (95% CI, 0.04-0.06), and the number needed to treat was 21.20 (95% CI, 18.10-24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to <85 years and in patients with comorbidities such as diabetes, or dementia.

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

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

Abstract 11813: Ten-year Risk of Atherosclerotic Cardiovascular Disease Predicts Long-Term Mortality in Lipid-Lowering Therapy

Background: The 10-year risk of atherosclerotic cardiovascular disease (ASCVD) can be effectively estimated by the ASCVD Risk Score derived from the pooled cohort equations. Current guidelines, thus, recommend primary prevention statin therapy based on ASCVD Risk Score while assessing effectiveness of statin therapy by targeting low-density lipoprotein cholesterol levels. It is unclear whether ASCVD Risk Score can also predict impact of statin therapy on mortality. Methods: A retrospective analysis of National Health and Nutrition Examination Survey (NHANES) (III and 1999-2008) linked to the National Death Index was conducted with propensity score matching. The study included 6647 adults without lipid-lowering therapy and 2484 with lipid-lowering therapy. Follow up was truncated at 10 years. Cox regression models and C statistics were used to assess the association between ASCVD Risk Score and mortality. Results: In the matched cohort with 4802 individuals with similar ASCVD risk profiles, ASCVD Risk Score was comparably predictive of all-cause mortality in the lipid-lowering therapy [area under curve (AUC)=0.75 ;95% confidence interval (CI)=0.73-0.77) and non-therapy (AUC=0.74; 95% CI=0.71-0.77) groups ( p =0.5). Similarly, the ASCVD Risk Score was comparably predictive of cardiovascular mortality in both groups (AUC=0.75; 95% CI=0.70-0.79 versus AUC=0.77; 95% CI=0.73-0.80; p =0.5). Lipid-lowering therapy was significantly associated with reduced all-cause mortality [adjusted hazard ratio (HR)=0.70; 95% CI=0.61-0.82; p &lt;0.01) and cardiovascular mortality (adjusted HR=0.65; 95% CI=0.51-0.83; p &lt; 0.01), particularly in those with an ASCVD Risk Score of ≥7.5%. Conclusions: ASCVD Risk Score comparably predicts mortality in individuals with and without lipid-lowering therapy. Individuals on lipid-lowering therapy had lower all-cause and cardiovascular mortality, compared to those without lipid-lowering therapy despite similar ASCVD Scores at baseline. These findings suggest that statin therapy may predictably reduce mortality in patients initiated on lipid lowering therapy for primary prevention based on the ASCVD Risk Score.

The effect of a multi-component behavior change technique intervention on medication adherence among individuals on primary prevention statin therapy: a dose-finding protocol

BackgroundIn the USA, the primary cause of death and morbidity continues to be cardiovascular disease (CVD). Numerous trials have shown that statin medication reduces the likelihood of CVD events; it is a cornerstone of CVD prevention. However, studies have also indicated that up to 60% of the estimated 26.8 million Americans prescribed primary prevention statin treatment are nonadherent during the first year. Multi-component behavioral change technique (BCT) therapies have shown moderate promise in improving medication adherence as well as other positive health behaviors (such as physical activity). However, no research has looked at the duration of multi-component BCT intervention needed to result in a clinically significant improvement in statin adherence behaviors. This study aims to determine the necessary dose of a multi-component BCT intervention (defined as duration in weeks) to promote adherence to statin medication among those on primary prevention statin treatment by utilizing the modified time-to-event continuous reassessment method (TiTE-CRM).Methods and designThe study will utilize the modified TiTE-CRM in 42 participants, recruited in 14 cohorts of 3 participants each. The goal of this analysis is to identify the minimum effective dose (MED) of a multi-behavior change technique (BCT) intervention required to increase adherence to statins by 20% between baseline and follow-up periods. Using the TiTE-CRM method, the dose of the behavior intervention in weeks will be assigned to each cohort based on the performance of the prior cohort. At the end of the study, the intervention dose that has been found to be associated with a 20% increase in statin adherence among 80% of participants assigned to that dose will be identified as the MED.DiscussionIf successful, the current trial will provide additional guidance to researchers and clinicians seeking to increase statin medication adherence using a BCT intervention by identifying the dose (i.e., the duration) of an intervention required to meaningfully increase adherence.Trial registrationClinicalTrials.gov NCT05273736. Registered on March 10, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05273736

Risk Factors for Vulnerable Plaque Detected Using Near-Infrared Spectroscopy in Patients Receiving Statin Therapy with No History of Coronary Artery Disease.

Residual risk of atherosclerosis remains high despite the use of lipid-lowering therapy with statins. Near-infrared spectroscopy intravascular ultrasound imaging (NIRS-IVUS) can identify vulnerable plaque via the detection of lipid-rich plaque. This study aimed to reveal the clinical characteristics of patients with vulnerable plaque despite statin therapy.NIRS-IVUS was used to determine the maximum 4 mm Lipid Core Burden Index (MaxLCBI4 mm) values of 38 de novo culprit lesions from 32 patients with acute coronary syndrome (53%) (mean age: 73.1 ± 13.1 years) who underwent percutaneous coronary intervention after a minimum 6 months of statin therapy for primary prevention. A patient with vulnerable plaque was defined as an individual presenting at least 1 target lesion with a vulnerable plaque (MaxLCBI4 mm > 400). Overall, the average low-density lipoprotein cholesterol (LDL-C) level was 95.5 ± 27.2 mg/dL. Patients in the vulnerable plaque group were younger and had higher LDL-C, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C) levels than those in the non-vulnerable plaque group. The MaxLCBI4 mm was positively correlated with LDL-C (P = 0.0002), triglycerides (P = 0.0003), and non-HDL-C (P = 0.0001). In multivariate analysis, all 3 treatable lipid components failed to show an independent relationship with the patients with vulnerable plaque. Using receiver-operating characteristics curve analysis, the cutoff points for LDL-C, triglycerides, and non-HDL-C were determined to be 78 mg/dL, 108 mg/dL, and 111 mg/dL, respectively, at MaxLCBI4 mm > 400. In conclusion, this study supports a more comprehensive and aggressive lipid-lowering therapy for the primary prevention of coronary artery disease.

Long-term statin therapy is associated with severe coronary artery calcification.

Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy. We established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of <60 ml/min/1.73 m2) were included in the adjustment models. The mean age of the study population was 64.7±7.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (>0-5 years, OR: 1.71 [CI: 1.34-2.18], p<0.001; >5-10 years, OR: 2.80 [CI: 2.01-3.90], p<0.001; >10 years, OR: 5.30 [CI: 3.23-8.70], p<0.001), and the relationship between statin duration and CACS remained significant after multivariate adjustment (>0-5 years, OR: 1.49 [CI: 1.16-1.92], p = 0.002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], p<0.001; >10 years, OR: 4.48 [CI: 2.7-7.43], p<0.001). Long-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.

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.

The effect of a multi-component behavior change technique intervention on physical activity among individuals on primary prevention statin therapy: A dose-finding trial protocol

BackgroundStatin therapy is a mainstay of cardiovascular disease (CVD) prevention, but research shows that statin therapy alone is insufficient for preventing incident CVD and mortality. Combining statin medication with increased physical activity (PA) can lower mortality risk more than either statin or PA alone. However, PA levels often remain the same and may even decline following statin prescription. Additional information is needed to identify how to increase PA among statin users and determine the minimal length of an intervention (i.e., intervention dose) necessary to increase PA. ObjectiveThe study aims to identify the required dose of a behavior change technique (BCT) intervention to increase PA among individuals on primary prevention statin therapy who have an elevated risk for cardiovascular disease (CVD). MethodsThe study will utilize the modified time-to-event continual reassessment method (TiTE-CRM) in 42 participants. We expect insights relating to dose-efficacy models and BCTs (Behavior Change Techniques) to improve PA in adults at risk for CVD. This trial will also examine potential mechanisms of action (MoAs) for interventions to increase PA, identify any effect a PA intervention may have on medication adherence, and determine whether participants respond uniformly to their respective behavioral interventions. Ethics and disseminationThis trial was approved by the Northwell Health Institutional Review Board (IRB) and all participants will complete informed consent. The trial results will be published in a peer-reviewed journal. All publications resulting from this series of personalized trials will follow the CONSORT reporting guidelines. Registration detailsThis trial is registered on www.ClinicalTrials.gov (Number NCT05273723).

S-17-4: EFFECTIVENESS OF STATIN INTENSIVE THERAPY IN TYPE 2 DIABETES WITH HIGH VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY

Objective: Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. Thus, we hypothesized that the benefit of intensive lipid-lowering therapy is larger in T2DM patients with high visit-to-visit SBP variability who are considered at higher risk. This study aimed to investigate the effectiveness of intensive versus standard statin therapy in primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability. Design and method: The EMPATHY study was the first randomized trial comparing statin intensive therapy targeting low- density lipoprotein cholesterol (LDL-C) &lt; 70 mg/dL and standard therapy targeting LDLC ®100 to &lt; 120 mg/dL in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within initial 6 months. The outcome was the composite incidence of cardiovascular events, including cardiac, cerebral, renal, and vascular events or death associated with cardiovascular events. Results: In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. The number of blood pressure measurements was 6.6 ± 1.6. The median value of SD and ARV of SBP was 9.78 mmHg and 10.29 mmHg, respectively. These median values were used as cutoffs. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45–0.90, p = 0.012) and 1.21 (95% CI 0.82–1.80, p = 0.34) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (p = 0.018). The analysis using ARV of SBP showed similar results (high ARV: hazard ratio 0.62, 95% CI 0.44–0.88, p = 0.008; low ARV: hazard ratio 1.15, 95% CI 0.78–1.70, p = 0.48; p for interaction = 0.022.). Conclusion: Statin intensive therapy targeting LDL-C &lt; 70 mg/dL had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit to visit SBP variability. Stratification based on visit-to-visit SBP variability might be a novel and useful strategy to determine the target LDL-C levels in statin lipid-lowering therapy among T2DM patients with microvascular complications.

Clinical encounter length and initiation of statin therapy for primary prevention among adults with elevated atherosclerotic cardiovascular disease risk

Clinical encounter length and initiation of statin therapy for primary prevention among adults with elevated atherosclerotic cardiovascular disease risk

Abstract 13548: Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes Mellitus

Background: The 2018 ACC/AHA Guidelines suggest patients with diabetes mellitus should receive moderate-high intensity statin therapy for primary prevention of ASCVD. We investigated diabetic and non-diabetic patients to evaluate the magnitude of benefit of guideline-directed statin intervention (GDSI) in each cohort. Methods: Primary prevention patients were categorized into diabetes (HbA1c&gt;6.5%) and no-diabetes and stratified based on 10-year ASCVD risk (Borderline [5%-7.4%], Intermediate [7.5-19.9%], or High [&gt;20%]). GDSI prior to first event was determined to be moderate to high intensity statin therapy for moderate and high-risk groups. Mean (±SD) time to start/change to GDSI was calculated from first interaction in health care. Cox regression assessed HRs of myocardial infarction (MI), stroke, and mortality with statin use. Results: Among 282,298 patients, 253,491 were non-diabetic and 28,807 had diabetes. Among diabetic patients at intermediate and high-risk, about 50% received GDSI initially, which rose to about two-thirds at 5y. In fully adjusted models, no statin use showed a higher risk of MI, stroke, and mortality compared to GDSI in all patients (Table). Compared to non-diabetics, diabetics on no statin versus GDSI had a higher risk of mortality and stroke in both intermediate risk [HR mortality 2.18 (1.79-2.65) vs 1.58 (1.45-2.72); all p&lt;0.01] and high risk [HR mortality 1.81 (1.58-2.07) vs 1.41 (1.26-1.57); all p&lt;0.01] groups (Table). Interaction analysis for mortality was significant (p&lt;0.001) by diabetes status. Low statin vs GDSI did not significantly increase risk of ASCVD, except for mortality in the high-risk diabetes group. Conclusions: Significant gaps remain in achieving GDSI, and diabetic patients not treated with GDSI have a higher risk for adverse outcomes, specifically mortality, than non-diabetics. We must develop more aggressive measures to achieve GDSI in all patients, particularly those at highest cardiovascular risk.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey

IntroductionThe United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 of adults aged 40–75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. ResultsAmong 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40–75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. ConclusionIn this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

Lipid-Lowering Therapy for Primary Prevention of Cardiovascular Disease: A Nationwide Analysis of 440,721 Patients

Lead Author's Financial Disclosures AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. Study Funding Esperion Therapeutics, Inc. Background/Synopsis Statins are indicated for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults with diabetes mellitus (DM), elevated 10-year risk, and those with LDL-C ≥190 mg/dL. Contemporary treatment patterns in community practice are not well described. Objective/Purpose To explore the use and dosing of statin therapy and use of several classes of non-statin lipid lowering therapies (LLT) in adults recommended for statins in primary prevention. Methods We identified adults recommended for primary prevention statin therapy who received outpatient care in 90 US health systems between 2017 and 2018 using a de-identified, electronic health record dataset; Cerner Real World Data. Primary prevention populations included: DM and age 40-75, calculated 10-year ASCVD risk ≥7.5% and age 40-75, and those with LDL-C ≥190 mg/dL or familial hypercholesterolemia based on diagnosis code. Medication data, including self-reported use of supplements, were examined. Based on the 2013 ACC/AHA Cholesterol Guideline (what was active at the time), patients were classified as: on appropriate- intensity statin, on under-dosed statin, or not on a statin. Results We identified 440,721 patients recommended for statins (median age 63 years, 50.1% male, and 75.5% white race), including (by mutually exclusive, hierarchical order) 308,620 (70%) patients with DM, 125,411 (28.5%) with a 10-year risk ≥7.5%, and 6,690 (1.5%) with LDL-C ≥190 mg/dL. Overall, 211,295 (47.9%) were on appropriate statin therapy, 29,039 (6.6%) were on lower-than-recommended statin intensity, and 200,387 (45.5%) were not on any statin (Figure). People with DM had the relative highest percent utilization of appropriate-dose statin (53.8%), while only 35.4% of those recommended for 10-year risk were on appropriate- dose statin, and only 12% of those with LDL-C ≥190 mg/dL were treated appropriately (Figure). Utilization of non-statin LLT was low overall across all three groups (15.8%). However, nearly one in ten (9.4%) of those recommended for primary prevention reported taking non-prescription Omega-3/fish oil supplements (Figure). Conclusions Over half of primary prevention patients at high risk for ASCVD in the US are not on appropriate-dose, guideline-recommended statin therapy. Of these, the majority were not on any statin. Non-statin LDL-C lowering medication use was also low. Despite no data for cardiovascular benefit, a substantial number of adults were taking non-prescription fish oil. There remains a strong national need to improve overall utilization and evaluate barriers to prescription/uptake of evidence based LLT in all patients eligible for primary prevention. AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Factors Associated with Discontinuation of Statin Therapy in Patients with Lymphoma Aged 80 Years and Older: A Retrospective Single-Institute Study.

BackgroundThere is little evidence to support or negate the benefits of statin therapy for primary prevention of cardiovascular disease (CVD) in lymphoma patients aged 80 years or older.ObjectiveWe evaluated comprehensive geriatric assessment (CGA) scores and previously reported risk factors for failure of statin therapy discontinuation in lymphoma patients aged 80 years and older with the aim of identifying those in whom discontinuation of statins for primary CVD prevention is indicated.Patients and methodsOur study cohort comprised 50 patients aged 80 years and older treated with chemotherapy for lymphoma at our institute from January 2011 to July 2020. We retrospectively analyzed the associations between CGA, including Geriatric 8, instrumental activities of daily living, and Charlson comorbidity index, and previously reported factors associated with failure of statin therapy discontinuation, defined as reintroduction of statins after their discontinuation, in this patient cohort.ResultsTwenty years or less of statin therapy was an independent predictor of failure of statin therapy discontinuation (hazard ratio 8.240, 95% confidence interval 1.380–49.10). There were significant differences in the rate of failure of statin discontinuation between patients receiving statins for ≥ 20 years versus < 20 years (p = 0.010). Multivariate analysis of CGA-related scores identified no significant risk factors for failure of statin discontinuation.ConclusionsDiscontinuation of statin therapy may be indicated in lymphoma patients aged 80 years and older who have used statins for 20 years or more.