Statin Initiation Research Articles

Pharmacists' impact on quality and financial metrics utilizing virtual care platforms during the coronavirus pandemic.

PurposeBecause of rising concern about coronavirus disease 2019 transmission, there has been a large shift from face-to-face, in-office visits to a virtual care model. The purpose of this article is to explain how Ascension Florida Gulf Coast was able to maximize the utility of ambulatory care pharmacists (ACPs) in the primary care setting during the pandemic and to provide guidance for creating a sustainable billing and practice model in the event of another global health crisis.SummaryBy employing telehealth services, our ACPs were able to continue to co-manage chronic disease states for documented diagnoses while still maintaining health-system revenue in the midst of a global health crisis. Utilizing various virtual platforms, ACPs were able to accommodate the needs of our patients while addressing concerns related to the compatibility and user friendliness of the platforms for our diverse patient population. ACPs used traditional incident-to evaluation and management services current procedural terminology billing codes with a virtual visit modifier for billing and tracking purposes.ConclusionUtilizing various virtual care platforms, our ACPs completed 447 patient encounters within the first 7 months of the pandemic. During this time, our ACPs addressed various population health metrics, specifically for patients diagnosed with diabetes without an active claim for a cholesterol-lowering medication, in addition to performing chronic disease management. Our ACPs had a 23% success rate for statin initiation in patients reviewed and contacted. By adopting virtual care options, our ACPs were able to effectively co-manage and educate patients while improving quality metrics and generating $50,662.24 in billable encounters for the health system during a global health crisis. The addition of ACP virtual encounters to primary care clinics both increases access to healthcare and improves patient care quality and outcomes while limiting revenue losses in our local health system.

Moderate-intensity statin use for primary prevention for more than 5 years is associated with decreased all-cause mortality in 75 years and older

ObjectiveEvidence regarding the primary preventive effects of statin in the elderly is inadequate. This study aimed to determine the duration and intensity of statins beneficial in adults aged ≥75 years for primary prevention. MethodsThis is a retrospective longitudinal study, using the National Health Insurance Corporation-Senior Cohort data from 2002 to 2015. Exact block matching was used to select comparable subjects from statin users and non-users. ResultThe study subjects consisted of 685 pairs of statin non-users and users (total number of 1,370). During the follow-up (mean 8.7 years) period, the adjusted HR for mortality compared to non-user was 0.95 (p = 0.71) in low intensity statin users and 0.80 (p = 0.002) in the moderate intensity statin groups. The adjusted HR for MACE (Major Adverse Cardiovascular Events) compared to non-users was 1.10 (p = 0.39) in the low intensity statin group and 1.29 (p = 0.001) in the moderate intensity statin group. The risk of MACE disappeared five years after in moderate intensity statin users. Moderate intensity statin use was significantly associated with an increased risk of NODM (New Onset Diabetes Mellitus) (HR 1.50, p < 0.001) for up to three years, but the risk faded away after five years (HR 0.90, p = 0.52). ConclusionModerate intensity statins taken for five or more years for primary prevention would be associated with low risk of all-cause mortality in the 75+ years old. This result may support the evidence that initiation of statin for primary prevention in patients aged over 75 years is beneficial and tolerable.

The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis.

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64–0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49–0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66–1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62–1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39–1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68–0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients.

Sex disparities in the effect of statins on lipid parameters: The PharmLines Initiative.

Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women.The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40 years at the index date: the date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes.Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted % MD 5.59, 95% confidence interval [CI] 2.42-8.75, P < .01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5 mmol/L.Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women.

Time to initiation of lipid-lowering drugs for subclinical atherosclerosis: sub-study of VIPVIZA randomized controlled trial, with single-arm cross-over.

AimsVisual information about subclinical atherosclerosis was provided to physicians and participants in the VIPVIZA trial, inclusion 2013–16 in northern Sweden, aiming to improve adherence to cardiovascular disease (CVD) prevention guidelines. Pictorial risk information may be more actionable. The aim of this study was to investigate the effect of intervention with pictorial risk information on time to first dispensing of statins.Methods and resultsAsymptomatic atherosclerotic disease was screened for by carotid ultrasound examination in 3532 participants enrolled in VIPVIZA, of those 3000 met the criteria for this study. Participants were randomly assigned to receive pictorial risk information consisting of graphical representation of atherosclerosis as compared to a control group without intervention. Time to initiation of statins was assessed during 5 years of follow-up through the National prescribed drug register. After 3 years, both groups were re-examined and received the intervention information. In the intervention group, initiation of statins increased considerably for the first 3 years and a smaller increase was also seen after re-intervention. After the cross-over, the control group showed a sharp increase in initiation of statins, almost reaching the same proportion treated at 5 years. The propensity to initiate statin treatment increased over the study period and there was no difference between men and women.ConclusionsThe pictorial information had an effect on time to initiation of statins, both as original and repeated intervention and also in the control group after single-arm cross-over. The current study supports pictorial information as a tool to shorten time to initiation of statins for CVD prevention.The VIPVIZA study is registered with ClinicalTrials.gov, number NCT01849575.

The association of statin subgroups with lower urinary tract symptoms following a prostate biopsy.

This was a secondary analysis aiming to assess whether hydrophilic or hydrophobic statins have a differential effect on urinary retention (UR) and lower urinary tract symptoms (LUTS) in men following a prostate biopsy (PBx), who were at risk for prostate cancer development. This was a population-based cohort study with data incorporated from the Institute for Clinical and Evaluative Sciences database to identify all Ontarian men aged 66 and above with a history of a single negative PBx between 1994 and 2016, with no drug prescription history of any of several putative chemo-preventative medications (statins, proton pump inhibitors, five-alpha-reductase inhibitors, and alpha-blockers). Multivariable Cox regression models with time-dependent covariates were used to assess the association of hydrophilic and hydrophobic statins with UR and LUTS within 30 days of a PBx. All models were adjusted for other known putative chemopreventive medications, age, rurality, pharmacologically treated diabetes, comorbidity score, and study inclusion year. Overall, 21 512 men were included, with a median followup time of 9.4 years (interquartile range [IQR] 5.4-13.4 years). Hydrophobic and hydrophilic statins were initiated by 30.7% and 19.6% of men, respectively, after the first negative PBx. UR and LUTS were experienced by 2.2% and 10% of men, respectively. Cox models demonstrated hydrophilic statins were associated with a lower risk of UR (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.38-0.83, p=0.0038) and LUTS (HR 0.86, 95% CI 0.76-0.98, p=0.022), while no such association was shown for hydrophobic statins. Initiation of hydrophilic statins in men older than 66 appears to be inversely associated with the risk of UR and LUTS within 30 days of a PBx.

Coronary Artery Calcium Versus Pooled Cohort Equations Score for Primary Prevention Guidance: Randomized Feasibility Trial

ObjectivesThis study sought to determine the feasibility of performing an extensive randomized outcomes trial comparing a coronary artery calcium (CAC)- versus a pooled cohort equations (PCE) risk score–based strategy for initiating statin therapy for primary atherosclerotic cardiovascular disease (ASCVD) prevention. BackgroundStatin therapy is standard for the primary prevention of ASCVD in subjects at increased risk. National guidelines recommend using the American College of Cardiology/American Heart Association PCE risk score to guide a statin recommendation. Whether guidance by a CAC score is equivalent or superior is unknown. MethodsCorCal (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events) was a randomized trial consenting 601 patients without known ASCVD, diabetes, or prior statin therapy recruited from primary care clinics and randomized to CAC- (n = 302) or PCE guidance (n = 299) of statin initiation for primary prevention. Enrolled subjects and their physicians made final treatment decisions. Primary outcomes compared the proportion of statin recommendations received and subject adherence over 1 year between CAC- and PCE-arm subjects. Modeled medical costs, adverse effects, and low-density lipoprotein–cholesterol (LDL-C) were additional measures of interest. ResultsSubjects were well matched, and 540 (89.9%) completed entry testing and received a protocol-based recommendation. A statin was recommended in 101 (35.9%) CAC-arm and 124 (47.9%) PCE-arm subjects (P = 0.005). Compared to PCE-based recommendations, CAC-arm subjects were reclassified from statin to no statin in 36.0% and from no statin to statin in 5.6% of cases, resulting in a total reclassification of 20.6%. Physicians accepted the study-dictated recommendation to start a statin in 88.1% of CAC-arm vs 75.0% of PCE-arm subjects (P = 0.01). Patient-reported adherence to this recommendation at 3 months was 62.2% vs 42.2%, respectively (P = 0.009). At 1 year, statin adherence remained superior, LDL-C levels were lower, estimated costs were similar or reduced in CAC subjects, and few events occurred. ConclusionsCAC guidance may be a more efficient, personalized, cost-effective, and motivating approach to statin initiation and maintenance in primary prevention. This feasibility phase of CorCal should be regarded as hypothesis-generating with respect to cardiovascular outcomes, which is being addressed in a large, longer-term outcomes trial. (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events [CorCal]; NCT03439267)

Abstract 9563: Preventive Therapy Changes Following Coronary Computed Tomography Angiography versus Invasive Coronary Angiography in Patients With Nonobstructive Coronary Artery Disease

Introduction: Coronary computed tomography angiography (CCTA) in SCOT-HEART led to increased preventive therapy for coronary artery disease (CAD). We hypothesized that atherosclerosis on CCTA would lead to greater preventive therapy changes compared to invasive coronary angiography (ICA). Methods: We studied 429 consecutive patients with available electronic health records and nonobstructive CAD (1-69% epicardial stenosis) by CCTA for assessment of chest pain or exertional dyspnea (n=143), ICA (n=142), or no CAD on CCTA (n=144). Changes in preventive therapies were assessed at 6 weeks and 6 months. Statin intensification was defined as change to greater LDL-lowering capacity. Intensification of antiplatelet agents, ACEI/ARB, or beta-blockers was defined as increased dose. Pairwise comparisons were made with Bonferroni adjustment. Results: There was no difference in age or gender in nonobstructive CAD patients ( Table ). ICA patients had more baseline therapies. Six week statin initiation was more common (p=0.006) in CCTA nonobstructive group, but not statin intensification (p=0.24) ( Table ). Six month LDL lowering was observed in CCTA (114±40 to 94±39 mg/dL, p&lt;0.001), but not ICA (95±41 to 87±36 mg/dL, p=0.10) nonobstructive patients. Younger age (OR 0.96; 95% CI 0.93-0.99, p=0.006), but not modality (CCTA compared to ICA OR 1.12; 95% CI 0.60-2.07, p=0.73) was associated with statin initiation or intensification at 6 weeks in nonobstructive patients. Greater change in therapies was found in nonobstructive patients by both modalities vs normal coronaries ( Table ). Conclusions: Nonobstructive CAD on CCTA is associated with greater statin initiation, but not intensification, at 6 weeks and lowering of LDL compared to ICA. Antiplatelet, beta-blocker, or ACEI/ARB prescriptions were not different in nonobstructive CAD by CCTA vs ICA. More preventive therapy changes occurred in nonobstructive CAD by either modality vs normal coronaries.

Abstract 11627: Effectiveness of Statin Therapy in an Urban Metropolitan Patient Population

Introduction: Severely elevated serum LDL (&gt;190 mg/dL) is an independent risk factor in the development of ASCVD complications. Despite current guidelines recommending the immediate initiation of high dose statin therapy in high-risk patients, limitations in care continue to exist, especially amongst different genders, races and populations with a higher burden of health disparities. Hypothesis: We assessed the hypothesis of whether or not race and gender affected the timeliness and appropriateness of initiating statin therapy in a patient population that has a higher burden of health disparities. Methods: We performed a single centered, retrospective observational study where 499 patients with an initial LDL level greater than 190 mg/dL were identified. These patients were then stratified according to race and gender and evaluated for intensity and timing of statin therapy for 12 months after their initial lipid profile. Institutional survey data was acquired to quantify health disparities of our patient population in comparison to US census and Chicago Public Health data. Results: All 499 patients were included in the study. The mean LDL was 224.72 mg/dL and the SEM was 1.775 mg/dL. When compared to state and national averages, respectively, patients from our geographic region were found to have a higher percentage of unemployment (11% vs 7% vs 7%), uninsured status (13% vs 9% vs 10%) and inadequate access to transportation (25% vs 11% vs 9%). There was no significant difference between race or gender regarding the timing of statin initiation or degree of statin intensity. Of all patients, 38.2% were not started on any statin while 29.8% were immediately started on statin therapy (p=0.04). Of those patients started on statin therapy, only 11.4% were started on a high intensity statin (p=0.039). Conclusions: In conclusion, we found that, regarding race or gender, there was no significant difference in initiation of statin or strength of statin started. However, the overall percentage of patients that were started on a timely and appropriate dosage was significantly lower, especially in comparison to national averages. This may be due to the high degree of health disparities that are prevalent amongst our patient population.

Abstract 11225: Comparison of Coronary Artery Calcium Scores in South Asians and Other Racial-Ethnic Groups

Introduction and Hypothesis: There is a disproportionately higher incidence of atherosclerotic cardiovascular disease (ASCVD) and associated adverse outcomes in South Asians (SA), compared to other races. SA ancestry has been identified as a risk enhancer in the US cholesterol guidelines. Coronary artery calcium (CAC), a validated marker of sub clinical atherosclerosis offers a robust assessment of CVD risk. We sought to compare the distribution of CAC scores as a marker of CVD risk, across various age groups in SA and other races/ethnicities. Methods: Our analyses included 33,663 individuals (517 SA, 24,060 whites, 1,509 African Americans (AA), 3,759 Hispanics, 3,818 Asians), who underwent CAC scoring at our center. CAC scores were stratified by age, across various races/ethnic sub-groups. Age groups were classified into quartiles as follows: &lt;51 years, 51-59 years, 59-67 years and &gt;67 years of age. Differences in median CAC across races/ethnicities were tested with the Kruskal-Wallis Test, by age quartiles as described. Results: Mean (SD) age was 59 (11.6) years and 63% were men in the entire cohort. SA over 67 years of age, had significantly higher median CAC score 354.0, Interquartile Range (IQR) 36 - 1476, compared to other race/ethnicities (Median CAC (IQR): whites, 195, (21-762), Hispanics 167.5, (19-779), Asians 144, (14-642), AA 159 (8.5-676) (P=0.0019). In age groups from 50-67 years of age, median CAC scores were not significantly different between these groups (Figure 1). Conclusions: In older age groups, SA have higher median CAC scores compared to whites and other racial/ethnic groups including AAs, Hispanics and other Asians. The observed differences in atherosclerotic burden provide mechanistic insights to higher CVD risk, in the vulnerable SA groups. Future studies should explore the effects of CAC screening on treatment strategies, such as initiation of statins and prognosis in SA.

Abstract 10918: Use of Mobile Health Technology in the Assessment of Statin-Associated Muscle Symptoms (SAMS)

Background: Statins are the cornerstone pharmacotherapy for lowering LDL-C and reducing risk of ASCVD. However, statin initiation and adherence are limited by statin-associated muscle symptoms (SAMS), posing significant clinical and public health dilemmas. Mobile health (mHealth) tools offer novel ways to assess real-time symptom data and share them back with patients to facilitate shared decision-making. Objective: To assess the feasibility and usability of an automated, text-message-based SAMS symptom-tracking platform to longitudinally track SAMS in patients who previously experienced muscle symptoms while on statin therapy. Methods: We enrolled 19 patients from 2 clinics at a single health system (Johns Hopkins; Baltimore, MD) and recorded baseline demographics, statin history and indication, perceptions of SAMS, and technology use via an online survey. Quantitative SAMS scores were gathered via daily text messages, and qualitative symptom data were collected in weekly text messages. Monthly symptom reports were sent to select participants via email on study days 30, 60 and 90. Upon study completion, participants reported perceptions of the study, the mHealth platform, and study measures via an online exit survey. Results: A total of 18 patients (aged 59.3 [SD 14.5] years, 67% women) collected data, and 15 patients completed the 90-day study protocol. Overall response rate to text messages was 91.5% (92.2% for daily SAMS messages, 86.0% for weekly muscle symptom prompts). Patients reported a statin adherence of 70%. Nine patients reported intolerable muscle symptoms at least once during the study, and intolerable symptom scores represented 3% of all reported symptom scores. Patients reported overall satisfaction with the study and found the SAMS scores helpful. Conclusions: Patients with previously reported SAMS successfully engaged with a text-message-based symptom-tracking platform with high interactivity and acceptability. This study demonstrates the feasibility and usability of an automated mHealth platform for longitudinally tracking SAMS in patients on statin therapy, and may provide a means for improving shared decision making to tailor statin therapy and improve adherence.

Abstract 12224: Predictive Power and Value of a CAD Polygenic Risk Score in Primary Prevention Based on Age and Clinical Risk

Background: The clinical utility of polygenic risk scores (PRS) for CAD has not yet been established. We investigated the ability of a CAD PRS to potentially guide statin initiation after accounting for age and clinical risk. Methods: We performed a prospective cohort study in the UK Biobank that included all individuals without a history of CAD and who were not on lipid-lowering therapy. The CAD PRS was comprised of 241 genome-wide significant SNPs. Genetic risk categories were defined as low (bottom 20%), intermediate, and high (top 20%). HRs were calculated as a function of age. Next, 10-year ASCVD risk score was used to classify individuals as low, borderline, intermediate, or high risk. Each ASCVD risk group was further stratified by genetic risk to determine whether genetics could reclassify individuals to help guide decisions regarding statin initiation with more precision. ASCVD events were defined as incident clinical CAD (including MI), stroke, or CV death. Results: The 333,245 patients included in this study were ages 40-74 years (avg 57) and 57% were female. Over the 10-yr follow-up, there were 4,552 MIs. The CAD PRS significantly predicted MI in all age groups but had significantly stronger risk prediction at younger ages (p-int &lt;0.001) ( Figure, A ). This gradient of risk was especially pronounced under 50 years of age, where those with high PRS approached a 6-fold increased risk of MI compared with those in the low PRS category. When CAD PRS testing was added to the 71,534 patients &lt;50 years old, 20% of borderline risk patients were reclassified into intermediate risk, warranting initiation of statin therapy to reduce LDL-C, and 20% of borderline and intermediate risk patients were reclassified as low risk, thus not warranting therapy ( Figure, B ). Conclusion: The predictive ability of a CAD PRS is especially strong in individuals under the age of 50 and can be used to identify more precisely who should be initiated on statin therapy.

Abstract 13604: Patient Centered Prescription Using Optimization Algorithms for Statin Users

Introduction: Clinical decision support (CDS) that does not optimize individual variability with best practice and treatment outcomes, cannot support patient-centered care. For example, a statin treatment CDS focused on cholesterol reduction without accounting for patient comorbidities, at risk lifestyle, or genetics, may well suggest a treatment that increases adverse effects, has a high cost, and has a low potential for improved outcome. We present a novel patient-centered decision support (PCDS) system for statin initiation that accounts for best practice and patient variation and ranks treatment options by their predicted ability to improve cardiac outcomes and reduce adverse effects for individual patients. Method: A total of 30 M de-identified claim records from 1.4 M adults receiving statin treatment over 1990-2020 are available in the OptumLabs® Data Warehouse and were used to train our counterfactual prediction algorithm. For a new patient, the PCDS system predicts LDL reduction, cardiac events, and other outcomes at 1 and 5 years, for every potential statin treatment. The PCDS then integrates doctor and patient preferences into a multi-objective optimization algorithm to generate a ranked list of treatment options. Conclusion: Our novel patient-centered decision support (PCDS) adds sophisticated AI modeling and optimization to account for evidenced-based best practice, patient variability, and adverse effect risk to produce a clear ranking of treatment options that can be re-ranked upon input of patient preferences and provider’s lifestyle, socioeconomics, culture, experience and environment factors. This PCDS approach leverages traditional CDS adjusted to individual preferences to aligned with the patient-centered care model.

Factors associated with time to initiation of a PCSK9 inhibitor after hospital discharge for acute myocardial infarction

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) lower atherosclerotic cardiovascular disease (ASCVD) event risk. Analyze patient characteristics associated with time to PCSK9i initiation following an acute myocardial infarction (AMI). We analyzed characteristics of patients ≥21 years of age in the Marketscan or Medicare databases who initiated a PCSK9i 0-89 days, 90-179 days, or 180-365 days after an AMI between July 2015 and December 2018 (n=1,705). We estimated the cumulative incidence of recurrent ASCVD events before PCSK9i initiation. Overall, 42%, 25%, and 33% of patients who initiated a PCSK9i did so 0-89 days, 90-179 days, and 180-365 days following AMI hospital discharge, respectively. Taking ezetimibe prior to AMI hospitalization and initiating ezetimibe within 30 days after AMI hospital discharge were each associated with a higher likelihood of PCSK9i initiation in the 0-89 days versus 180-365 days post-discharge (adjusted odds ratio [OR] 1.83, 95% confidence interval [95%CI] 1.35-2.49 and 1.76, 95%CI 1.11-2.80, respectively). Statin use before and statin initiation within 30 days after AMI hospitalization were associated with a lower likelihood of PCSK9i initiation 0-89 days versus 180-365 days post-discharge (adjusted OR 0.64, 95%CI 0.49-0.84 and 0.39, 95%CI 0.28-0.54, respectively). Overall, 8.0%, 10.5%, and 12.5% of patients had an ASCVD event at 90, 180, and 365 days following AMI hospital discharge and before initiating a PCSK9i, respectively. Among patients initiating a PCSK9i after AMI, a low proportion did so within 89 days of hospital discharge. Many patients had a recurrent ASCVD event before treatment initiation.

A Cost-Consequence Analysis of Preemptive SLCO1B1 Testing for Statin Myopathy Risk Compared to Usual Care.

There is a well-validated association between SLCO1B1 (rs4149056) and statin-associated muscle symptoms (SAMS). Preemptive SLCO1B1 pharmacogenetic (PGx) testing may diminish the incidence of SAMS by identifying individuals with increased genetic risk before statin initiation. Despite its potential clinical application, the cost implications of SLCO1B1 testing are largely unknown. We conducted a cost–consequence analysis of preemptive SLCO1B1 testing (PGx+) versus usual care (PGx−) among Veteran patients enrolled in the Integrating Pharmacogenetics in Clinical Care (I-PICC) Study. The assessment was conducted using a health system perspective and 12-month time horizon. Incremental costs of SLCO1B1 testing and downstream medical care were estimated using data from the U.S. Department of Veterans Affairs’ Managerial Cost Accounting System. A decision analytic model was also developed to model 1-month cost and SAMS-related outcomes in a hypothetical cohort of 10,000 Veteran patients, where all patients were initiated on simvastatin. Over 12 months, 13.5% of PGx+ (26/193) and 11.2% of PGx− (24/215) participants in the I-PICC Study were prescribed Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline-concordant statins (Δ2.9%, 95% CI −4.0% to 10.0%). Differences in mean per-patient costs for lipid therapy prescriptions, including statins, for PGx+ compared to PGx− participants were not statistically significant (Δ USD 9.53, 95% CI −0.86 to 22.80 USD). Differences in per-patient costs attributable to the intervention, including PGx testing, lipid-lowering prescriptions, SAMS, laboratory and imaging expenses, and primary care and cardiology services, were also non-significant (Δ− USD 1004, 95% CI −2684 to 1009 USD). In the hypothetical cohort, SLCO1B1-informed statin therapy averted 109 myalgias and 3 myopathies at 1-month follow up. Fewer statin discontinuations (78 vs. 109) were also observed, but the SLCO1B1 testing strategy was 96 USD more costly per patient compared to no testing (124 vs. 28 USD). The implementation of SLCO1B1 testing resulted in small, non-significant increases in the proportion of patients receiving CPIC-concordant statin prescriptions within a real-world primary care context, diminished the incidence of SAMS, and reduced statin discontinuations in a hypothetical cohort of 10,000 patients. Despite these effects, SLCO1B1 testing administered as a standalone test did not result in lower per-patient health care costs at 1 month or over 1 year of treatment. The inclusion of SLCO1B1, among other well-validated pharmacogenes, into preemptive panel-based testing strategies may provide a better balance of clinical benefit and cost.

HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study.

The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality. This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins. In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%). A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens. Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

Impact of cumulative exposure to LDL cholesterol on cardiovascular events in patients with familial hypercholesterolemia

Abstract Aims Recent studies suggest that cumulative exposure to LDL-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population. We aimed to determine whether cholesterol-year-score, an indicator of cumulative exposure to LDL-C, is associated with ASCVD events among Japanese patients with FH Methods and results We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis who were referred to our institute between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis / statin initiation] + LDL-C at inclusion × [age at inclusion − age at diagnosis / statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1–17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio [HR], 1.35; 95% confidence interval, 1.07–1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 versus 0.889; P=0.00473). Conclusion Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients. Funding Acknowledgement Type of funding sources: None.

Association of Statin Therapy Initiation With Diabetes Progression

Statin therapy has been associated with increased insulin resistance; however, its clinical implications for diabetes control among patients with diabetes is unknown. To assess diabetes progression after initiation of statin use in patients with diabetes. This was a retrospective matched-cohort study using new-user and active-comparator designs to assess associations between statin initiation and diabetes progression in a national cohort of patients covered by the US Department of Veterans Affairs from fiscal years 2003-2015. Patients included were 30 years or older; had been diagnosed with diabetes during the study period; and were regular users of the Veterans Affairs health system, with records of demographic information, clinical encounters, vital signs, laboratory data, and medication usage. Treatment initiation with statins (statin users) or with H2-blockers or proton pump inhibitors (active comparators). Diabetes progression composite outcome comprised the following: new insulin initiation, increase in the number of glucose-lowering medication classes, incidence of 5 or more measurements of blood glucose of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes. From the 705 774 eligible patients, we matched 83 022 pairs of statin users and active comparators; the matched cohort had a mean (SD) age of 60.1 (11.6) years; 78 712 (94.9%) were men; 1715 (2.1%) were American Indian/Pacific Islander/Alaska Native, 570 (0.8%) were Asian, 17 890 (21.5%) were Black, and 56 633 (68.2 %) were White individuals. Diabetes progression outcome occurred in 55.9% of statin users vs 48.0% of active comparators (odds ratio, 1.37; 95% CI, 1.35-1.40; P < .001). Each individual component of the composite outcome was significantly higher among statin users. Secondary analysis demonstrated a dose-response relationship with a higher intensity of low-density lipoprotein-cholesterol lowering associated with greater diabetes progression. This retrospective matched-cohort study found that statin use was associated with diabetes progression, including greater likelihood of insulin treatment initiation, significant hyperglycemia, acute glycemic complications, and an increased number of prescriptions for glucose-lowering medication classes. The risk-benefit ratio of statin use in patients with diabetes should take into consideration its metabolic effects.

Atherosclerotic cardiovascular disease thresholds for statin initiation among people living with HIV in Thailand: A cost-effectiveness analysis.

People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand. Our decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35-75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk ≥10% (control), ≥7.5% and ≥5%. A statin initiation threshold of ASCVD risk ≥7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold ≥10%, at an extra cost of 3,539 Baht ($US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ($US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk ≥5% to ≥7.5% was 349,000 Baht ($US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ($US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold ≥7.5% becoming cost-effective compared with current practice. Reducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

Early impact of 2018 AHA/ACC/Multisociety Cholesterol Guideline on lipid monitoring after statin initiation

Lead Author's Financial Disclosure: Nothing to disclose.