Benefit Of Statin Use Research Articles

The association of statin use with in-hospital mortality in patients with acute kidney injury during hospitalization: A retrospective analysis.

Acute kidney injury (AKI) is a severe condition in hospitalized patients and carries high mortality. The influence of statin use on the outcomes of AKI patients remains inconsistent. We aimed to discover the association between statin use and in-hospital mortality. This retrospective study screened all adult admissions in Peking University First Hospital between 1 January 2018 and 31 December 2020, and patients with AKI during hospitalization were included. Exposure was defined as any statin prescription prior to AKI onset. Patients were followed up until death or discharge. The primary outcome was in-hospital all-cause mortality; secondary outcomes included cardiovascular- and sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery at discharge. A total of 2034 AKI patients were included. 551 (27%) patients were statin users. During a median of 10 days of follow-up, we documented 283 (14%) in-hospital deaths. Compared with statin nonusers, statin users experienced a significantly lower risk in in-hospital all-cause mortality (adjust hazard ratio [aHR], 0.54; 95% CI, 0.35-0.84) and cardiovascular-related mortality (aHR, 0.48; 95% CI, 0.24-0.97) after covariate adjustment. The survival benefit of statin use was consistent across subgroups, that is, age, sex, initial AKI stage and major surgery (all P for heterogeneity >.05). For sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery, the association was no longer significant in the fully adjusted model. For any type of statins, a statistically significant association was only observed in atorvastatin (aHR, 0.49; 95% CI, 0.30-0.81). Statin use may improve survival, and atorvastatin may be preferred in patients with AKI.

Association between the use of statins and in-hospital mortality risk in patients with sepsis-induced coagulopathy during ICU stays: a study based on medical information mart for intensive care database

BackgroundThe objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC).MethodsUtilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission.ResultsDuring the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60–0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34–0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33–0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15–0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P < 0.05).ConclusionThe present study supports the potential benefits of statin use in mortality in SIC patients during ICU stays. The study encourages clinicians to consider the benefits of statins and supports the ongoing exploration of statins for enhanced outcomes in critical care settings.

Statin use in total joint arthroplasty: a systematic review

Introduction: There has been increased interest in the use of Statins in total hip and knee arthroplasty (THA and TKA) patients to improve outcomes and reduce postoperative complications. This study was performed to systematically review the evidence on Statin use in total joint arthroplasty, specifically its benefits and complications. Methods: Adhering to the PRISMA guidelines, a systematic review of PubMed, Embase, Scopus, Web of Science, and the Cochrane database was performed to find studies reporting on the effects of Statin use on outcomes of THA and TKA. Two authors independently selected relevant papers to include. Results: A total of 18 papers were included in the final analysis. Most were retrospective studies, with heterogeneous patient selection and outcome measures. The evidence on the risks and benefits of Statin use on outcomes of total joint arthroplasty was very limited and heterogeneous. Studies were focusing on perioperative cardiac outcomes, clinical outcomes and complications, renal, pulmonary, and gastrointestinal outcomes. Due to the heterogeneity of reported data, a formal meta-analysis was not possible. Conclusions: There is some evidence in the literature suggesting that perioperative use of Statins, especially in Statin-naïve patients, may reduce cardiac (e.g. atrial fibrillation) and noncardiac (e.g. delirium) complications, while not increasing the risk of muscle or liver toxicity. The authors also found low levels of evidence that Statin use may reduce the long-term risk for revision surgery and osteolysis.

The association between trajectory of serum cholesterol, statin dosage, and the risk of recurrent biliary stone diseases

BackgroundStatins may reduce the risk of recurrent gallstone disease by decreasing bile cholesterol saturation and pathogenicity. However, limited studies have investigated this issue. This study aimed to assess whether statin doses and serum cholesterol levels were associated with a decreased risk of recurrent biliary stone diseases after the first event index, with a follow-up time of 15 years. MethodsBased on the Chang Gung Research Database (CGRD) between January 1, 2001, and December 31, 2020, we enrolled 68,384 patients with the International Classification of Diseases, Ninth and Tenth Revision codes of choledocholithiasis. After exclusions, 32,696 patients were divided into non-statin (<28 cDDD, cumulative defined daily doses) (n = 27,929) and statin (≥28 cDDD) (n = 4767) user groups for analysis. Serum cholesterol trajectories were estimated using group-based trajectory modeling (n = 8410). ResultsThe statin users had higher Charlson Comorbidity Index (CCI) scores than the non-statin users. Time-dependent Cox regression analysis showed that statin use >365 cDDD was associated with a significantly lower risk of recurrent biliary stones (adjusted hazard ratio [aHR] = 0.28, 95% CI, 0.24–0.34; p < 00.0001), acute pancreatitis (aHR = 0.24, 95% CI, 0.17–0.32, p < 00.0001), and cholangitis (aHR = 0.28, 95% CI, 0.25–0.32, p < 00.0001). Cholecystectomy was also a protective factor for recurrent biliary stones (aHR = 0.41, 95% CI, 0.37–0.46; p < 00.0001). The higher trajectory serum cholesterol group (Group 3) had a lower risk trend for recurrent biliary stones (aHR = 0.79, p = 0.0700) and a lower risk of cholangitis (aHR = 0.79, p = 0.0071). ConclusionThis study supports the potential benefits of statin use and the role of cholecystectomy in reducing the risk of recurrent biliary stone diseases.

Causal Analyses of Statin to Prevent Liver Disease Progression: A Nationwide Study Using Superlearning Targeted Maximum Likelihood Estimation

Many studies have shown that statins reduce the risk of progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) among at-risk populations. However, causality has not been proved. This study examined whether statins could prevent LC and HCC in patients with progressive and worsening chronic liver disease, using a robust methodology for causality. Between 2002 and 2013, 52,145 patients with chronic liver diseases were identified from the National Health Insurance Service database in South Korea. The inverse probability weighting (IPW) and superlearning targeted maximum likelihood estimation (TMLE) were used to assess the causality of statin use on the risk of LC and HCC, adjusting for sex, age, comorbidities, and co-medications. Multivariable superlearning TMLE revealed that statin use was associated with reduction in the incidence risk of LC (Marginal odds ratio (MOR) 0.59, 95% confidence interval [CI] 0.50-0.65) and HCC (MOR 0.59, 95% CI 0.50-0.67). Such a protective effect was more evident with atorvastatin and lipophilic statin. This population-based observational study indicated the benefit of statin use, particularly atorvastatin and lipophilic statin, for causally reducing the risk of LC and HCC.

Cardiovascular Benefit of Statin Use Against Air Pollutant Exposure in Older Adults.

Little is known about the cardiovascular benefit of statin use against ambient air pollution among older adults who are at higher risk of cardiovascular disease (CVD) potentially owing to age-related declines in cardiovascular functions along with other risk factors. This retrospective, population-based cohort study consisted of adults aged 60 years and older free of CVD at baseline identified from the National Health Insurance Service (NHIS) database linked to the National Ambient Air Monitoring Information System (NAMIS) for average daily exposure to PM10 and PM2.5 in 2015 in the major metropolitan areas in the Republic of Korea. Follow-up period began on January 1, 2016 and lasted until December 31, 2021. Cox proportional hazards model was used to evaluate association of cardiovascular benefit with statin use against different levels of air pollutant exposure. Of 1,229,444 participants aged 60 years and older (mean age, 67.4; 37.7% male), 377,076 (30.7%) were identified as statin-users. During 11,963,322 person-years (PY) of follow-up, a total of 86,018 incident stroke events occurred (719.0 events per 100,000 PYs). Compared to statin non-user exposed to high level of PM10 (>50 µg/m3) and PM2.5 (>25 µg/m3), statin users had 20% (adjusted hazard ratio [HR], 0.80; 95% confidence intervals [CI], 0.75 to 0.85) and 17% (adjusted HR, 0.80; 95% CI, 0.80 to 0.86) lower adjusted risk of incident stroke for PM10 and PM2.5, respectively. Similar risk reduction for incident CVD was also found among statin-users exposed to low or moderate level of PM10 (≤50 µg/m3) and PM2.5 (≤25 µg/m3) exposure. Among adults aged 60 years and older with high and low or moderate levels of exposure to PM10 and PM2.5, statin use was associated with a significantly lower risk of stroke.

Association between pre-ICU statin use and ARDS mortality in the MIMIC-IV database: a cohort study.

Acute respiratory distress syndrome (ARDS) is a severe condition associated with high morbidity, mortality, and healthcare costs. Despite extensive research, treatment options for ARDS are suboptimal. This study encompassed patients diagnosed with ARDS from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Pre-intensive care unit (ICU) statin use was assessed as the exposure variable. Kaplan-Meier survival analysis was conducted to evaluate mortality at 30 and 90 days. Adjusted multivariable Cox models were utilized to estimate hazard ratios. Subgroup analyses and propensity score-matching (PSM) were undertaken for further validation. Our study comprised 10,042 participants diagnosed with ARDS, with an average age of 61.8 ± 15.3 years. Kaplan-Meier survival analysis demonstrated a significantly lower prevalence of mortality at 30 and 90 days in individuals who used statins before ICU admission. Adjusted multivariable Cox models consistently showed a significant decrease in mortality prevalence associated with pre-ICU statin use. After accounting for confounding factors, patients who used statins before ICU admission experienced a 39% reduction in 30-day mortality and 38% reduction in 90-day mortality. We found a significant decrease in ICU stay (0.84 days) for those who used statins before ICU admission. These results were supported by subgroup analyses and PSM. This large cohort study provides evidence supporting the association between pre-ICU statin use, reduced risk of death, and shorter ICU stay in patients with ARDS, thereby suggesting the potential benefits of statin use in critically ill patients.

Protective Effects Against Dementia Undergo Different Statin Type, Intensity, and Cumulative Dose in Older Adult Type 2 Diabetes Mellitus Patients

ObjectivesThis study investigated the relationship between statin use and dementia risk in older adults with type 2 diabetes (T2DM). It also assessed the impact of various statin types, dosage intensity, and cumulative doses on dementia risk. DesignEmploying the inverse probability of treatment weighting (IPTW) Cox hazards model, this research explored the influence of statin utilization on dementia incidence. Setting and ParticipantsThe study included older adult T2DM patients aged 60 years or older who received statins (case group) and those who did not (control group) during the follow-up period. MethodsThe IPTW Cox hazards model quantified the association between statin use and dementia incidence. Subgroup analyses investigated different statin types, usage intensity, and cumulative dose–dependent relationships with dementia risk, measured by adjusted hazard ratios (aHRs) with corresponding 95% CIs. ResultsStatin users experienced a significant reduction in dementia risk (aHR: 0.47, 95% CI: 0.46-0.48). Subgroup analysis using IPTW Cox regression revealed varying dementia incidence reductions among users of different statin types, with aHRs (95% CIs) ranging from 0.09 to 0.69. Multivariate analyses unveiled a dose-dependent relationship, showing reduced dementia incidence based on cumulative defined daily doses (cDDDs) per year. The corresponding aHRs (95% CIs) were 0.20 to 0.72 across quartiles 4 to 1 of cDDD-years, with a significant trend (P < .001). The optimal daily statin use was 0.88 defined daily doses (DDDs), associated with the lowest dementia risk. Conclusions and ImplicationsStatins significantly reduced dementia risk in older adult T2DM patients. Higher cumulative defined daily doses (cDDD-years) were linked to more substantial risk reductions. This research underscores the clinical benefits of statin use in preventing dementia in this population and calls for further investigation into the underlying mechanisms. It also raises the possibility of influencing policy decisions to manage dementia risk in this vulnerable group.

Pregnancy-related adverse events associated with statins: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications. Research design and methods Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab). Results A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22–4.95; IC025 = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65–6.54; IC025 = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56–16.56; IC025 = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab. Conclusions Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.

Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to multiorgan insufficiency and death, particularly among the older adults. Statins have been suggested as potentially protective drugs due to their pleotropic effects, but the actual benefit of statin use among the older population in this setting is not clear. This study aimed to evaluate the association between preadmission statin use and the presentation and clinical outcomes of hospitalized COVID-19 patients older than 70 years of age.MethodsA historical cohort study of all patients above 70 years of age who were hospitalized with COVID-19 infection in a large academic hospital between March and August 2020 was performed. The association between preadmission statin use and patients’ presentation and adverse outcome was studied. Adverse outcome was defined as any of the following: shock, invasive or non-invasive ventilation, organ insufficiency, myocardial infarction, cerebrovascular accident, in-hospital or 30-day post-admission mortality, hospital stay longer than the median length of stay of all COVID-19 patients, referral to nursing home or rehabilitation center.ResultsSeventy-two (44%) of the 163 studied patients (median age 82 years, 45% males) had been preadmission treated with statins. The statin-treated patients (STP) had a higher prevalence of diabetes (40% vs 24%, p = 0.028) and cardiovascular disease (58% vs. 34%, p = 0.002). Seventy two percent of the STP had adverse outcome, compared to 86% of the non-STP (p = 0.033). After adjustment for potential confounders, prior statin use was associated with decreased risk for an adverse outcome (odds ratio = 0.4, 95% confidence interval 0.18–0.92, p = 0.03).ConclusionsThe preadmission use of statins was associated with a lower risk of adverse outcome in older adults hospitalized with COVID-19. Continuation of statin treatment might be implemented for risk reduction of adverse outcomes in the older population in the era of new SARS-CoV-2 variants and less effective vaccines.

Patient-oriented risk score for predicting death 1 year after myocardial infarction: the SweDen risk score

ObjectivesOur aim was to derive, based on the SWEDEHEART registry, and validate, using the Western Denmark Heart registry, a patient-oriented risk score, the SweDen score, which could calculate the risk...

Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function

BackgroundLipid-lowering therapy with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition are effective strategies in reducing cardiovascular disease risk; however, concerns remain about potential long-term adverse neurocognitive effects. ObjectivesThis genetics-based study aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes. MethodsWe extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of low-density lipoprotein cholesterol and performed drug-target Mendelian randomization, proxying the potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition using a range of outcomes to capture the complex facets of cognition and dementia. ResultsUsing data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area. Conversely, we observed several adverse associations for HMGCR inhibition with lowered cognitive performance (beta: –0.082; 95% CI: –0.16 to –0.0080; P = 0.03), reaction time (beta = 0.00064; 95% CI: 0.00030-0.00098; P = 0.0002), and cortical surface area (beta = –0.18; 95% CI: –0.35 to –0.014; P = 0.03). Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer’s disease progression or Lewy body dementia risk. Consistency of findings across Mendelian randomization methods accommodating different assumptions about genetic pleiotropy strengthens causal inference. ConclusionsUsing a wide range of cognitive function and dementia endpoints, we failed to find genetic evidence of an adverse PCSK9-related impact, suggesting a neutral cognitive profile. In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.

Statins in Pregnancy: Can We Justify Early Treatment of Reproductive Aged Women?

Statins are the pillar of secondary prevention in reducing cardiovascular disease in high-risk adults. However, statin discontinuation is the standard recommendation in pregnant and lactating patients. This review evaluates whether we can justify the early treatment of reproductive aged women with statin therapy. Statins have several potential benefits including its antioxidant, anti-inflammatory, and anti-thrombogenic properties that may prevent the worsening of atherosclerosis in high-risk women. Nevertheless, most studies on statins and teratogenicity have a limited sample size and the effects of long-term statin use on fetal and neonatal health remain unknown. Not all statins may be safe and pravastatin's cholesterol-lowering properties may be too limited to provide much maternal benefit in pregnancy. While emerging evidence supports the use of pravastatin in pregnancy, we need to better assess the risk of early cardiovascular disease and acute progression of atherosclerosis before and during pregnancy to better understand the risks and benefits of statin use.

Usefulness of Statins as Secondary Prevention Against Recurrent and Terminal Major Adverse Cardiovascular Events

Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p=0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p=0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy.

Study links statins with more aggressive diabetes progression

Patients with diabetes who used statins experienced less control of their diabetes than patients who did not take statins, suggests a new retrospective study published in JAMA Internal Medicine. Individuals who had diabetes and were prescribed statins had a higher chance of insulin treatment initiation, were more likely to develop significant hyperglycemia and experience acute glycemic complications, and were more likely to be prescribed extra glucose-lowering medications, according to the study results. The overall increase in diabetes progression was 37% more compared to patients not taking statins. “Given this increase, I was not surprised by the increased number of patients needing glucose-lowering medications or insulin,” said Kristi Kelley, PharmD, BCPS, BCACP, a clinical professor at Auburn University Harrison School of Pharmacy in Alabama. “I was surprised by the results of the secondary analysis showing that the odds of progression of diabetes was greatest with the high intensity statins.” The study authors note that the “findings of the secondary analyses should be interpreted as exploratory.” Statins are among the most-prescribed medications and are known to be associated with greater insulin resistance and higher blood glucose levels. FDA added a warning to all statins in 2012 that states that increases in A1C and fasting blood glucose have been noted in patients receiving statin therapy. In their 2019 scientific statement, the American Heart Association (AHA) also acknowledged adverse events related to statins. “This is something that is going to continue to be investigated and will be discussed among health care providers,” said Kelley. In the JAMA Internal Medicine study, Mansi and colleagues analyzed 12 years (2003–2015) of data on patients covered through the VA health system. The study included roughly 83,000 propensity-scored matched pairs of statin users and nonusers. Since data originated within the VA health system, the overwhelming majority of participants were white men around 60 years old, which could limit the external validity of the results, according to Kelley. The medical record data included inpatient and outpatient diagnoses and procedure codes, pharmacy and medication usage, vital signs records, and laboratory data. For those who filled a statin prescription during the study period, roughly 63% of the prescriptions were for simvastatin; 12% for atorvastatin; 11% for rosuvastatin; and 10% for pravastatin. Lead author Ishak Mansi, MD, said patients should not stop taking their statin, but rather discuss it with their health care provider. While no single study should change practice, he said this research may alert clinicians to keep a close eye on the blood glucose of patients who initiate statins. “The biggest implication for this study is that further research is urgently needed to define the diabetes subpopulation that would benefit most from statin use and the subpopulation that may suffer most harm,” said Mansi, who is a staff internist at the VA North Texas Health System. Jingchuan Guo, MD, PhD, an assistant professor in the Department of Pharmaceutical Outcomes and Policy at the University of Florida College of Pharmacy, said she would like to see further research on this topic, specifically concerning the potential effect variation across individual drugs within the therapeutic class of statins, the individualized effect of stains on diabetes progression in real-world populations and subgroups, the risk-benefit of using (or not using) statins for long-term cardiovascular health outcomes among patients with diabetes, and whether the increased risk of diabetes progression is linked with statin use or with lower LDL cholesterol. Kelley said it will be important for pharmacists and other health care providers to be prepared to have discussions with patients about the risk-benefit of statins. “The decision to initiate a statin or continue a statin will need to be an individualized patient-centered decision,” she said. The study authors noted that “the higher risk of diabetes progression associated with statin use may seem less consequential, at least in the short and intermediate term, than the cardiovascular benefits of statin use, especially when used for secondary prevention. However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention.” With over 34 million Americans currently living with diabetes, Guo said these types of studies have major public health relevance. Mansi noted that with statins in clinical use for more than 30 years, he would have expected such research to be done much sooner.

Obesity-Specific Association of Statin Use and Reduced Risk of Recurrence of Early Stage NSCLC

IntroductionStatins, used for their lipid-lowering activity, have anti-inflammatory and anticancer properties as well. We evaluated this potential benefit of statin use in patients with NSCLC. MethodsAll 613 patients with pathologic stage 1 or 2 NSCLC who had lobectomy without neoadjuvant therapy at our institution during 2008 to 2015 were included. Association between presurgery statin use and overall survival and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression. Association of statin use with tumor transcriptome was evaluated in another 350 lung cancer cases. ResultsUnivariable analyses did not reveal a statistically significant association of statin use with either overall survival or RFS, with hazard ratio equals to 1.19 and 0.70 (Wald p = 0.28 and 0.09), respectively. In subgroup analyses, significantly improved RFS was found in statin users, but only in overweight/obese patients (body mass index [BMI] > 25; n = 422), with univariable and multivariable hazard ratio of 0.49 and 0.46 (p = 0.005 and 0.002), respectively, but not in patients with BMI less than or equal to 25 (n = 191; univariable p = 0.21). Transcriptomes of tumor statin users had high expression of tumoricidal genes such as granzyme A and interferon-γ compared with those of nonusers among high- but not low-BMI patients with lung cancer. ConclusionsOur study suggests that statins may improve the outcome of early stage NSCLC but only in overweight or obese patients. This benefit may stem from a favorable reprogramming of the antitumor immune response that statins perpetrate specifically in the obese.

Long-Term Statin Use, Total Cholesterol Level, and Risk of Colorectal Cancer: A Prospective Cohort Study.

Statin use has been examined as a potential chemopreventive strategy against colorectal cancer (CRC). Previous studies have not been able to investigate this topic with adequate follow-up time or disentangle the effects of statin use and total cholesterol level. We investigated prospectively this topic. Eligible participants (100,300 women and 47,991 men) in the Nurses' Health Study and Health Professionals Follow-Up Study were followed for up to 24 years. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 2,924 incident CRC cases during follow-up. In fully adjusted analyses, longer duration of statin use was associated with higher risk of colon cancer (hazard ratios, the 95% confidence interval was 1.09, 0.95-1.25 for 1-5 years; 1.16, 0.99-1.36 for 6-10 years; 1.08, 0.81-1.44 for 11-15 years; 1.85, 1.30-2.61 for >15 years; vs never users, P = 0.004 for trend) rather than rectal cancer. The risk elevation was driven by proximal colon cancer (1.16, 0.98-1.38 for 1-5 years; 1.19, 0.98-1.45 for 6-10 years; 1.25, 0.89-1.74 for 11-15 years; 2.17, 1.46-3.24 for >15 years; vs never users, P = 0.001 for trend) rather than distal colon cancer. The results remained robust in analyses among participants with hypercholesterolemia or who never received screening. Total cholesterol level was not associated with CRC risk. This study does not support benefit of statin use in CRC chemoprevention or any association between total cholesterol level and CRC risk. On the contrary, long-term statin use may be associated with increased colon cancer risk (driven by proximal colon cancer).

Abstract LB091: Long-term statin use and risk of colorectal cancer: A prospective cohort study

Abstract Importance Statin use has been examined as a potential chemopreventive strategy against colorectal cancer (CRC), with conflicting findings reported. Prior studies have not been able to investigate this topic with adequate follow-up time. Objective To examine prospectively the association between long-term statin use and CRC risk. Design setting and participants The Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) are large prospective cohorts of US women and men. Participants who were alive and free of cancer at the time when information on their statin use was first assessed were eligible for inclusion (100,300 women and 47,991 men), and were followed for up to 26 years (NHS: 1994-2016; HPFS: 1990-2016). Exposures Overall status and duration of statin use. Main outcome and measures Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for exposures and CRC risk. Results We documented 2,924 incident CRC cases during follow-up. In fully-adjusted analyses, compared to participants who never used statins, longer duration of statin use was associated with higher risk of overall CRC (HR, 95%CI was 1.09, 0.98-1.20 for ever use; 1.06, 0.94-1.19 for 1 to 5 years; 1.10, 0.96-1.27 for 6 to 10 years; 1.10, 0.86-1.41 for 11 to 15 years; 1.56, 1.13-2.16 for &amp;gt;15 years; vs. never users, P=.02 for trend). The risk elevation was driven by proximal colon cancer (1.22, 1.05-1.41 for ever use; 1.17, 0.99-1.39 for 1 to 5 years; 1.21, 0.99-1.48 for 6 to 10 years; 1.27, 0.91-1.78 for 11 to 15 years; 2.22, 1.49-3.30 for &amp;gt;15 years; vs. never users, P&amp;lt;.001 for trend) rather than cancers of distal colon or rectum. The results became more robust in sensitivity analyses among participants with hypercholesterolemia. Conclusion and relevance This study does not support benefit of statin use in CRC chemoprevention. Long-term statin use was associated with increased CRC risk (predominantly driven by proximal colon cancer). Citation Format: Yin Zhang, Andrew T. Chan, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Long-term statin use and risk of colorectal cancer: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB091.

Statin Use Is Associated with Decreased Mortality in Multiple Myeloma— a SEER Medicare Study

IntroductionStatins are a groups of drugs used in the treatment of hyperlidemia and in primary and secondary prevention of cardiovascular disease. Recently, there has been increasing interest in statins for their ability to improve survival and reduce risk of cancer due to their pleiotropic effects. Observational studies have reported survival benefit among patients with several cancers including pancreatic cancer, ovarian cancer and colorectal cancer. It has also been shown to reduce incidence risk in hematologic malignancies including lymphoid neoplasms. Recently, Sanfillipo et al (J Clin Oncol 2016 34:4008-4014) reported that statin use among patients with Multiple Myeloma (MM) was associated with decreased mortality in a Veteran Affairs (VA) database. We attempted to replicate these findings among older patients with MM using data from SEER-Medicare database.MethodsAll cases of MM diagnosed 2008-2013 in the SEER-Medicare claims were extracted along with their associated Medicare claims data from 2007-2014. Incomplete cases including: those diagnosed prior to age 65, death certificate or autopsy cases, and those not enrolled in Medicare Part A (inpatient), B (outpatient), and D (prescription) were excluded. Cases of suspected smoldering MM, those without MM defining “CRAB” symptoms and not treated within 6 months following diagnosis, were excluded using a pre-established algorithm (Fakhri, et al,Blood 2016 128:2348). Statin users, defined as having 2 or more prescriptions for statins within 1 year before and after diagnosis of MM, were identified by Part D claims. ICD-9 codes were used to identify patients with chronic kidney disease (CKD). Charlson comorbidity index (CCI) was calculated using a previously established algorithm. Receipt of novel MM agents as first-line therapy and stem cell transplant and bisphosphonate utilization within 1 year following diagnosis were defined as the presence or absence of the corresponding ICD-9 and HCPCS codes. Baseline characteristics were compared between statin users and non-users by Chi-square test and Student's T-test as appropriate. Multivariate analysis was performed by Cox proportional hazard modeling method. Statin exposure was also assessed as a time-dependent covariate to account for immortal time bias. All statistical analysis was performed using SAS software 9.4 (Cary, NC, USA)Results5935 patients were included in the study of which 1779 were statin users. Descriptive data is shown in table 1. Statin users tended to be slightly older, had a higher rate of CKD and higher mean CCI, but were slightly more likely to undergo ASCT (Autologous stem cell transplant). In the survival analysis, statin use (time-dependent) was associated with decreased mortality with an adjusted hazard ratio of (aHR- 0.91, 0.85-0.98, p=0.008). Use of novel agents, bisphosphonates, and stem cell transplant were all associated with decreased mortality; increasing age and CCI were associated with increased mortality. The full multivariate results are shown in table 2.ConclusionsStatins as a class of drugs exert their effect on mevalonate pathway by inhibiting HMG-CoA reductase for their cholesterol lowering effect and this disruption of mevalonate pathway has also been shown to induce apoptosis in MM cells. In vitro studies of MM cells have also shown to induce cell death and decrease proliferation when exposed to statins. This susceptibility of MM cells to statins in laboratory experiments has been further supported by findings in retrospective studies with Epstein et al (Int. J. Cancer 2017 141: 480-487) reporting reduced incidence of MM with statin use and Sanfillipo et al showing decreased mortality with statin use among patients with MM.In the present study we found that statin use decreased mortality by 9%. Our results are similar to the findings reported by Sanfillipo et al and further support a potential benefit of statin use among patients with MM. These results should be evaluated further in prospective clinical trials. [Display omitted] DisclosuresVij:Celgene: Honoraria; Konypharma: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Meyers-Squibb: Honoraria; Jazz: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Research Funding. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy.

Age-Related Trajectories of Cardiovascular Risk and Use of Aspirin and Statin Among U.S. Adults Aged 50 or Older, 2011-2018.

To examine age-related trajectories of cardiovascular risk and use of aspirin and statin among U.S. adults aged 50 or older. Repeated cross-sectional study using data from 2011 to 2018 National Health and Nutrition Examination Surveys. Nationally representative health interview survey in the United States. Non-institutionalized adults aged 50 years and older (n=11,392 unweighted). Primary prevention was defined as the prevention of a first cardiovascular event including coronary heart disease, angina/angina pectoris, heart attack, or stroke, whereas secondary prevention was defined as those with a history of these clinical conditions. Medication use was determined by self-report; aspirin use included dose and frequency, and statin use included generic names, days of prescription fills, and indications. We examined linear trends between age and each medication use, after controlling for period, sex, and race/ethnicity. Prevalence of those eligible for primary prevention treatment increased with age from 31.8% in ages 50-54 to 52.0% in ages ≥75 (p < 0.001). Similarly, those eligible for secondary prevention treatment increased with age from 2.7% in ages 50-54 to 21.1% in ages ≥75 (p < 0.001). Low-dose daily aspirin use increased with age (p < 0.001), and 45.3% of adults aged ≥75 took low-dose aspirin daily for primary prevention. Statin use also increased with age (p < 0.001), and 56.4% of adults aged ≥75 had long-term statin use for secondary prevention. While adults aged ≥75 do not benefit from the use of aspirin to prevent the first CVD, many continue to take aspirin on a regular basis. In spite of the clear benefit of statin use to prevent a subsequent CVD event, many older adults in this risk category are not taking a statin. Further education and guidance for both healthcare providers and older adults regarding the appropriate use of aspirin and statins to prevent CVD is needed.