Receiving Statin Therapy Research Articles

Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Abstract Background Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear. Purpose To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer. Methods We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1. Results We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p<0.00001; Figure 1B). Conclusion In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.

Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice

Abstract Background and Aims Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics. Methods A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England. Results The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients. Conclusions The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.

Three decades of lipid-lowering therapy in type 2 diabetic patients with angiographically proven stable coronary artery disease

Abstract Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Impact of statin use in head and neck cancer: a nested case-control study.

Dyslipidemia and statin use are associated with an increased risk of various cancers. However, the association in head and neck cancer (HNC) remains unclear. Therefore, this study aimed to investigate the impact of dyslipidemia and statin use on the development of HNC. Using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019, we compared two groups HNC patients (n = 1006) and matched control participants (n = 4024) after propensity score overlap weighted balancing. The odds ratios (ORs) for HNC development according to dyslipidemia and statin use duration were assessed using propensity score overlap-weighted multivariable logistic regression. Individuals with untreated dyslipidemia had significantly lower odds of developing HNC than those of normal participants (OR 0.70, 95% confidence interval [CI] 0.59-0.82). Conversely, patients with dyslipidemia who received statin therapy (< 60days) showed a nearly two-fold increase in the odds of HNC (OR 1.94, 95% CI 1.29-2.90). Long-term statin use (≥ 60days) aligned the odds with those of normal participants (OR 0.89, 95% CI 0.76-1.04). The adverse effect of short-term statin use on HNC development requires further study, and long-term statin use for dyslipidemia treatment does not increase the odds of HNC.

Impact of statins on incidence of gastrointestinal bleeding events among patients with continuous-flow left ventricular assist devices.

Patients with continuous flow left ventricular assist devices (CF-LVADs) are at increased risk of gastrointestinal bleeding (GIB). Statins are commonly prescribed in LVAD patients for cardiovascular disease prevention. However, their impact on GIB events is controversial. Importantly, literature regarding statins impact on GIB in CF-LVAD patients is lacking. A single-center, retrospective review of adult patients who underwent CF-LVAD implantation between May 2016 and January 2020 was performed. Patients were categorized based on statin use throughout the study period. The primary outcome was the composite of arteriovenous malformation confirmed GIB and major GIB events for up to 1-year post-LVAD implantation. Of 123 patients included in the final analysis, 66 (54%) received statin therapy during the study period. No difference was observed in the primary outcome between the statin and control groups (RR: 1.73; 95% CI: 0.75-3.98; p=0.20). Multivariable Cox regression revealed that older age and higher baseline creatinine were associated with an increased risk of GIB within 1-year of CF-LVAD implantation. Among patients with CF-LVADs, there was no significant difference in the incidence of major GIB events associated with the use of statin therapy. Further studies are needed to assess whether a true association exists.

The impact of statins on melanoma survival: a systematic review and meta-analysis.

Statin use may decrease recurrence and improve survival in patients with melanoma. In this systematic review and meta-analysis, we examine the current body of literature concerning the use of statins as an adjunctive therapy in melanoma, Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to April 2023. Studies were included if they compared patients with melanoma receiving and not receiving statin therapy concurrently with their oncologic treatment in terms of long-term oncologic outcomes. The primary outcome was 5-year overall survival (OS). Meta-analyses was performed with DerSimonian and Laird random effects. Risk of bias was assessed with the ROBINS-I and GRADE was used to assess certainty of evidence. From 952 citations, eight non-randomized studies were identified. Included studies were conducted between 2007 and 2022. Random effects meta-analysis of adjusted hazard ratios from three studies suggested an improvement in 5-year OS with statin use with wide 95% confidence intervals (CIs) crossing the line of no effect (hazard ratio 0.87, 95% CI: 0.73-1.04, P = 0.12, I2 = 95%, very-low certainty). Outcome reporting was heterogeneous across all other oncologic outcomes such that pooling of data was not possible. Risk of bias was serious for seven studies and moderate for one study. This systematic review of studies evaluating the impact of statin use on survival in patients with melanoma found a 13% reduction in risk of death at 5 years from diagnosis - a point estimate suggesting benefit. However, the wide 95% CIs and resultant type II error risk create significant uncertainty.

Характеристика факторів серцево-судинного ризику в пацієнтів з артеріальною гіпертензією, які приймають подвійну комбінацію антигіпертензивних препаратів: результати дослідження ФАКТОР-дуо

The aim – to study the characteristics of cardiovascular risk factors, the structure and effectiveness of treatment in hypertensive patients (pts) on the background of a dual combination of antihypertensive drugs, to evaluate the efficacy and tolerability of calcium channel blockers (CCB) (amlodipine and lercanidipine) when added to the combination of renin-angiotensin-aldosterone system (RAAS) inhibitor with a diuretic.Materials and methods. A multicenter study with 1616 hypertensive pts who received dual combination antihypertensive therapy. Cardiovascular risk factors were studied (smoking status, alcohol consumption, physical activity, family history of cardiovascular disease), concomitant cardiovascular diseases, carbohydrate metabolism disorders, and body mass index were determined, and current antihypertensive therapy and its effectiveness were evaluated based on office blood pressure (BP) measurements. Amlodipine 5-10 mg/day or lercanidipine 10–20 mg/day was added to the combination of RAAS blocker with a diuretic in the case of office BP ≥ 140/90 mm Hg. 1198 hypertensive pts received triple combined therapy. The effectiveness and tolerability of the treatment were evaluated after 4 weeks according to data from office BP measurements and home BP monitoring (HBPM). Lercanidipine was taken by 76 % of pts and amlodipine was taken by 24 % of pts.Results and discussion. Hypertensive pts were characterized by a significant prevalence of obesity (38.6 %), smoking (27.9 %), and insufficient physical activity (31.2 %). A significantly higher percentage of smoking and alcohol consumption was registered among men, while a lower level of physical activity was registered among women. Concomitant type 2 diabetes was present in almost a quarter of pts, stroke/TIA in 8.7 %, and myocardial infarction/revascularization in 8.3 %. At the same time, 53.2 % of the pts received statin therapy, and 64.7 % received antiplatelet drugs.Conclusions. The addition of CCB contributed to office BP target achievement in 69.1 % of pts, and optimal BP according to HBPM data in 54.3 % of pts. Lercanidipine and amlodipine have demonstrated comparable antihypertensive efficacy. Lercanidipine demonstrated a better tolerability profile compared to amlodipine: the incidence of side effects was significantly lower, respectively, 3.6 vs. 12.3 %; edema of the lower legs occurred in 6.5 times more often under amlodipine treatment than lercanidipine.

Effect of statin administration on the inflammatory response of monocytes in patients with atherosclerosis

Currently, statins are the main preparations of anti-atherosclerotic therapy due to a number of effects that reduce the progression of atherosclerosis, including anti-inflammatory effectiveness. The purpose of this study was to evaluate the inflammatory response of monocytes in patients with severe atherosclerosis during therapy with hydrophilic and lipophilic statins, as well as in patients with atherosclerosis not receiving lipid-lowering therapy. A total of 60 patients with severe atherosclerosis of the coronary arteries were included in the study in three groups: 1) receiving atovastatin therapy for at least 12 months before inclusion in the study, n = 20; 2) receiving rosuvastatin therapy for at least 12 months before inclusion in the study, n = 20; and 3) those who had not received statin therapy within a year before inclusion in the study, n = 20. The primary culture of monocytes from study participants was obtained by gradient centrifugation followed by immunomagnetic separation of CD14+ monocytes. The isolated cells were cultured for 7 days without stimulation and with pro-inflammatory stimulation using lipopolysaccharide (LPS). The level of basal, LPS-stimulated and re-stimulated secretion of TNFα and IL-1β was determined by enzyme immunoassay. Basal secretion of TNFα and IL-1β in patients receiving statins was lower than in patients who did not receive statins for a year; the secretion of both cytokines was significantly lower in the rosuvastatin group. LPS-stimulated TNFα secretion was significantly lower in the groups of patients receiving statins; IL-1β secretion was significantly lower in the atorvastatin and rosuvastatin groups compared to the group without statins. Re-stimulated IL-1β secretion did not differ significantly between groups; re-stimulated TNFα secretion was significantly lower in the rosuvastatin group compared to the atorvastatin and non-statin groups. Thus, the results of the study demonstrate the anti-inflammatory effectiveness of rosuvastatin, expressed in a decrease in the secretion of pro-inflammatory cytokines by cultured monocytes/macrophages of patients with severe coronary atherosclerosis.

Association between Estimated Small Dense Low-Density Lipoprotein Cholesterol and Occurrence of New Lesions after Percutaneous Coronary Intervention in Japanese Patients with Stable Angina and Receiving Statin Therapy.

Low-density lipoprotein cholesterol (LDL-C) is considered the most important risk factor for coronary artery disease (CAD). Although lipid-lowering therapy using high-intensity statins for patients with stable CAD is one of the cornerstones of medication therapy, there is still a risk of residual cardiovascular events, even after controlling for LDL-C. Recently, attention has focused on the association between small dense LDL-C as a residual risk factor for CAD, and it has been reported that a formula can be used to calculate the small LDL-C. We investigated the association between estimated small dense LDL-C (Esd LDL-C) and the occurrence of new lesions with myocardial ischemia 2 years after percutaneous coronary intervention (PCI) in 537 patients with stable angina who underwent PCI. In this study, all patients had been prescribed statins. This study was based on previously reported data regarding the relationship between non-high-density lipoprotein cholesterol levels and stable angina pectoris after PCI. Revascularization, including new lesions and in-stent restenosis, and new lesions appeared in 130 and 90 patients, respectively, 2 years after PCI. Age, diabetes mellitus (DM), LDL-C, and Esd LDL-C were associated with the occurrence of revascularization and new lesions 2 years after PCI. Multivariate logistic regression analysis models revealed that Esd LDL-C [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.004-1.048, p = 0.020; and OR 1.03, 95% CI 1.009-1.057, p = 0.007, respectively] were associated with the revascularization and occurrence of new lesions 2 years after PCI. As well as total cholesterol and LDL-C, Esd LDL-C was an independent risk factor for the revascularization and occurrence of new lesions 2 years after PCI for stable angina in Japanese patients receiving statin therapy. In patients with stable angina who are on lipid-lowering therapy with statins, calculating the Esd LDL-C may provide useful information for predicting revascularization and the occurrence of new lesions.

Adjunctive Statin Therapy in Patients with Covid-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundThe efficacy and safety of adjunctive statin therapy in hospitalized patients with coronavirus disease 2019 (Covid-19) remains uncertain. MethodsWe systematically searched Medline, Embase, Cochrane, and ClinicalTrials.gov databases from inception to late April 2024 for randomized controlled trials (RCTs) comparing statin versus no statin use in patients hospitalized with Covid-19. We pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) applying a random-effects model. R version 4.3.1 was used for statistical analyses. ResultsWe included 7 RCTs comprising 4,262 patients, of whom 2,645 (62%) were randomized to receive statin therapy. Compared with no statin, statin use significantly reduced case-fatality rate (RR 0.88; 95% CI 0.80-0.98; I2 = 0%). In a time-to-event analysis, we found similar results (HR 0.86; 95% CI 0.75-0.99; I2 = 0%). Statin use also significantly reduced World Health Organization (WHO) scale at 14 days (mean difference -0.27; 95% CI -0.54 to -0.01; I2 = 0%). There was no statistically significant difference between the two groups in length of hospital stay, elevation of liver enzymes, and C-reactive protein levels. ConclusionsIn patients hospitalized with Covid-19, statins significantly reduced case-fatality rate and WHO scale score. RegistrationA prospective register was recorded in International Prospective Register of Systematic Reviews (PROSPERO) with the number CRD42023479007.

Transporter Genes and statin-induced Hepatotoxicity.

Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55-0.69), and it was increased to 0.71 in Model II (95% CI: 0.64-0.77). This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.

Australian and New Zealand Living Guideline cholesterol-lowering therapy for people with chronic kidney disease (CARI Guidelines): Reducing the evidence-practice gap.

People with chronic kidney disease experience high rates of cardiovascular disease. Cholesterol-lowering therapy is a mainstay in the management but there is uncertainty in the treatment effects on patient-important outcomes, such as fatigue and rhabdomyolysis. Here, we summarise the updated CARI Australian and New Zealand Living Guidelines on cholesterol-lowering therapy in chronic kidney disease. We updated a Cochrane review and monitored newly published studies weekly to inform guideline development according to international standards. The Working Group included expertise from nephrology, cardiology, Indigenous Health, guideline development and people with lived experience of chronic kidney disease. The guideline recommends people with chronic kidney disease (eGFR ≥15 mL/min/1.73 m2) and an absolute cardiovascular risk of 10% or higher should receive statin therapy (with or without ezetimibe) to reduce the risk of cardiovascular events and death (strong recommendation, moderate certainty evidence). The guidelines also recommends a lower absolute cardiovascular risk threshold (≥5%) for Aboriginal and Torres Strait Islander Peoples and Māori with chronic kidney disease to receive statin therapy (with or without ezetimibe) (strong recommendation, low certainty evidence). The evidence was actively surveyed from 2020-2023 and updated as required. No changes to guideline recommendations were made, with no new data on the balance and benefits of harms. The development of living guidelines was feasible and provided the opportunity to update recommendations to improve clinical decision-making in real-time. Living guidelines provide the opportunity to transform chronic kidney disease guidelines.

GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health)

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Elevated GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy individuals. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and two interval CAC assessments between 2010 through 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC > 0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 μmol/L, and the incidence of CAC was 13.1% (280/2,129). GlycA level odds ratio (OR) for CAC incidence was 1.002 [95% confidence interval (CI) 1.0005-1.005, p=0.016] adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and comorbidities. The GlycA (≤p25 vs ≥p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p=0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

Association between statin use and acute pulmonary embolism in intensive care unit patients with sepsis: a retrospective cohort study.

Acute pulmonary embolism (APE) is a life-threatening medical condition that is frequently encountered and associated with significant incidence and mortality rates, posing a substantial threat to patients' well-being and quality of life. Sepsis is prominent independent risk factor for the development of APE. Despite recent investigations indicating a reduced APE risk through statin therapy, its impact on patients with sepsis and APE remains unresolved. The Medical Information Mart for Intensive Care (MIMIC)-IV database was utilized to identify patients diagnosed with sepsis and APE, irrespective of statin treatment status, as part of this study. The primary study aim was to assess the risk of APE, which was analyzed using multivariate logistic regression models. The study encompassed a total of 16,633 participants, with an average age of 64.8 ± 16.2 years. Multivariate logistic regression revealed that septic patients receiving statin therapy in the intensive care unit (ICU) exhibited a 33% reduction in the risk of developing APE (OR = 0.67, 95% CI: 0.52-0.86, p < 0.001). The findings of further analyses, including stratification based on statin usage, dosage, and propensity score matching, consistently reinforced the hypothesis that administering statins to patients with sepsis effectively mitigates their potential APE risk. The results of the study provide compelling evidence in favor of administering statins to septic patients as a prophylactic measure against APE, given that statins may reduce the risk of developing APE, and their anti-APE effect appears to be dose-dependent. Nonetheless, future randomized controlled trials are needed to validate these results.

Exposure to statin therapy decreases the incidence of venous thromboembolism after trauma.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE. We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted January 2018 - June 2022 were included. Patients on prehospital anticoagulants, history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched to non-users by statin use indications including age, current heart and cardiovascular conditions and history, hyperlipidemia, injury severity, and body mass index. Time to in-hospital statin initiation and occurrence of VTE and other complications within 60 days were collected. Differences between groups were determined by univariate, multivariable logistic regression, and Cox proportional hazard analyses. Of 3,062 eligible patients, 79 were statin users that were matched to 79 non-users. There were no differences in admissions demographics, vital signs, injury pattern, transfusion volumes, lengths of stay, or mortality between groups. The overall VTE incidence was 10.8% (17/158). Incidence of VTE in statin users was significantly lower (3%) than non-users (19%; P = 0.003). Differences between statin users and non-users were observed for rates of DVT (0% vs 9%), PE (3% vs 15%), and sepsis (0% vs 5%). Exposure to statins was associated with an 82% decreased risk of developing VTE (hazard ratio = 0.18, 95% CI 0.04 - 0.86; P = 0.033). Statin exposure was associated with decline in VTE and lower individual rates of DVT, PE, and sepsis. Our findings indicate that statins should be evaluated further as a possible adjunctive therapy for VTE chemoprophylaxis after traumatic injury. Level III, Retrospective Cohort Study.

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.

Different Statin Dosages and Their Effects on Osteoporosis

The aim of the study was to investigate the effect of different doses of statins on the progression of osteoporosis during a 36-month follow-up period. The study included 98 postmenopausal women diagnosed with osteoporosis and the presence of atherosclerosis of lower limb arteries. Patients were divided into 2 groups: women who received statins as part of atherosclerosis treatment (group 1, n=53) and those who did not receive statin therapy for hyperlipidemia (group 2, n=45). After 36 months of follow-up, patients were divided into two groups — with unfavorable (n=42) and favorable (n=56) course of osteoporosis. Progression of osteoporosis was considered unfavorable if during the follow-up period the patients had low traumatic fractures of large bones and/or progressive decrease in bone mineral density (BMD). Depending on the statin dose taken, patients were divided into groups: 1) those taking atorvastatin 20 mg or rosuvastatin 10 mg; 2) those taking atorvastatin 40 mg or rosuvastatin 20 mg. The results revealed a significant association between statin therapy and a favorable course of osteoporosis (OR=0.316, 95% C.I. =0.137-0.727, p=0.003). The use of higher doses of statins (atorvastatin 40 mg or rosuvastatin 20 mg) was associated with the development of low traumatic fractures of large bones and/or progressive decrease in MPC during 36 months of follow-up (OR=3.0, 95% C.I.=1.119-8.040, p=0.030). On the other hand, the use of lower doses of statins (20 mg atorvastatin or 10 mg rosuvastatin) was associated with a favorable course of osteoporosis (OR=0.047, 95% C.I.=0.010-0.212, p=0.030). The dose of statin taken was also moderately negatively correlated with IPC (r=−0.45; p=0.005). Thus, the use of statins for a long period (36 months) in low doses (atorvastatin 20 mg or rosuvastatin 10 mg) is an effective and safe method of treating cardiovascular comorbidities represented by atherosclerosis of lower limb vessels and osteoporosis in postmenopausal women and is characterized by a reduced risk of osteoporosis-related large bone fractures.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Statin-Induced Rhabdomyolysis: A Rare Case

ABSTRACT Statins are a group of lipid-lowering agents currently used as mainstay agents in the primary and secondary prevention of atherosclerotic cardiovascular heart disease. Rhabdomyolysis is one of the rare adverse effects of statin therapy, the incidence of which increases in the presence of risk factors. We report a rare case of statin-induced rhabdomyolysis presenting with acute kidney injury (AKI) requiring dialysis in the absence of risk factors. A 58-year-old diabetic and hypertensive female presented with pain and weakness of lower limbs, difficulty in walking, shortness of breath, and decreased urine output. She was receiving statin therapy for the past 1 week. Her blood investigations showed elevated creatine phosphokinase (CPK) and renal parameters. Electromyography and magnetic resonance imaging of thigh and calf muscles were suggestive of myositis. Statin was withdrawn and hemodialysis was done. The patient recovered gradually with no residual deficit. Statin-induced rhabdomyolysis is a rare but serious adverse effect requiring timely management. CPK levels along with thorough history and physical examination are useful to establish the diagnosis. Treatment is hydration and supportive therapy when diagnosed early. Hemodialysis is required in severe cases with AKI.

The Cycle study: a prospective study on cholesterol levels during the menstrual cycle

Abstract Background Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management. Purpose To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol. Methods In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2). Results Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase. The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2). Conclusions In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2