Association Between Statin Use and Postoperative Mortality in Older Patients with Hip Fractures

Association Between Statin Use and Postoperative Mortality in Older Patients with Hip Fractures | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 21 January 2026 V1 Latest version Share on Association Between Statin Use and Postoperative Mortality in Older Patients with Hip Fractures Authors : Ling Lee , Shu-Han Chuang , Cheng-Hsien Chang , Yi-Jie Kuo , Lien-Chen Wu , Yu-Zhi Lian , and Yu-Pin Chen 0000-0002-9729-6375 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176902044.40784229/v1 161 views 54 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Purpose Hip fracture mortality remains persistently high despite surgical advances. Statins have demonstrated pleiotropic anti-inflammatory and antithrombotic effects, yet their peri-operative benefit remains controversial. The purpose of this study was to evaluate the association between pre-operative statin use and one-year mortality in older hip fracture patients, and to determine whether any survival benefit was accompanied by reductions in mechanistically related complications. Methods This retrospective cohort study utilized the TriNetX US Collaborative Network to identify patients aged 65–85 years undergoing hip fracture surgery between 2013 and 2024. Propensity score matching (1:1) was performed to balance baseline characteristics between chronic statin users and non-users (n = 5,708 per group). The primary outcome was one-year all-cause mortality. Secondary outcomes included stroke, cardiac arrest, venous thromboembolism (VTE), pneumonia and sepsis. Results Pre-operative statin use was associated with a significantly reduced risk of one-year mortality (HR 0.72; 95% CI 0.65–0.81; p < 0.001), evident as early as one month post-surgery. However, this immediate survival benefit was not accompanied by significant reductions in mechanistically relevant complications, including stroke, cardiac arrest, VTE, pneumonia or sepsis (all p > 0.05). Sensitivity analyses yielded consistent results. Conclusion The temporal dissociation between reduced mortality and unchanged complication rates suggests that the observed survival benefit likely reflects baseline systemic stability and the ’healthy user effect’ rather than direct acute pharmacological protection. While statins remain indicated for long-term cardiovascular prevention, our data do not support initiating statins solely to improve short-term peri-operative survival in this catabolic population. makecell, tabularx makecell, tabularx Association Between Statin Use and Postoperative Mortality in Older Patients with Hip Fractures makecell, tabularx makecell, tabularx Running title: Statin Use and Hip Fracture Mortality Ling Lee 1,2 , Shu-Han Chuang 3 , Cheng-Hsien Chang, 3,4 , Yi-Jie Kuo 5,6 , Lien-Chen Wu 5,6,7 , Yu-Zhi Lian 8 , Yu-Pin Chen 5,6 * 1 School of Medicine, National Defense Medical University, Taipei, Taiwan. 2 Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan. 3 Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan. 4 Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. 5 Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 6 Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 7 Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan. 8 School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan. Corresponding author: Yu-Pin Chen , MD, PhD ORCID ID: Yu-Pin Chen [0000-0002-9729-6375] makecell, tabularx makecell, tabularx Address: Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Email : [email protected] makecell, tabularx makecell, tabularx Statements and Declarations Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. not-yet-known not-yet-known not-yet-known unknown Competing interests The authors declare no competing interests. makecell, tabularx makecell, tabularx Author contributions Ling Lee, Shu-Han Chuang, and Yu-Pin Chen contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ling Lee and Yu-Pin Chen. The first draft of the manuscript was written by Ling Lee and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. makecell, tabularx makecell, tabularx Data availability The data that support the findings of this study are available from TriNetX. Restrictions apply to the availability of these data, which were used under license for the current study. not-yet-known not-yet-known not-yet-known unknown Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of Changhua Christian Hospital (No. 250612). Consent to participate The requirement for informed consent was waived by the Institutional Review Board of Changhua Christian Hospital due to the retrospective nature of the study and the use of de-identified data. Consent to publish Not applicable. not-yet-known not-yet-known not-yet-known unknown not-yet-known not-yet-known not-yet-known unknown Purpose Hip fracture mortality remains persistently high despite surgical advances. Statins have demonstrated pleiotropic anti-inflammatory and antithrombotic effects, yet their peri-operative benefit remains controversial. The purpose of this study was to evaluate the association between pre-operative statin use and one-year mortality in older hip fracture patients, and to determine whether any survival benefit was accompanied by reductions in mechanistically related complications. makecell, tabularx makecell, tabularx Methods This retrospective cohort study utilized the TriNetX US Collaborative Network to identify patients aged 65–85 years undergoing hip fracture surgery between 2013 and 2024. Propensity score matching (1:1) was performed to balance baseline characteristics between chronic statin users and non-users (n = 5,708 per group). The primary outcome was one-year all-cause mortality. Secondary outcomes included stroke, cardiac arrest, venous thromboembolism (VTE), pneumonia and sepsis. makecell, tabularx makecell, tabularx Results Pre-operative statin use was associated with a significantly reduced risk of one-year mortality (HR 0.72; 95% CI 0.65–0.81; p < 0.001), evident as early as one month post-surgery. However, this immediate survival benefit was not accompanied by significant reductions in mechanistically relevant complications, including stroke, cardiac arrest, VTE, pneumonia or sepsis (all p > 0.05). Sensitivity analyses yielded consistent results. Conclusion The temporal dissociation between reduced mortality and unchanged complication rates suggests that the observed survival benefit likely reflects baseline systemic stability and the ’healthy user effect’ rather than direct acute pharmacological protection. While statins remain indicated for long-term cardiovascular prevention, our data do not support initiating statins solely to improve short-term peri-operative survival in this catabolic population. Keywords Hip fracture, Statin, Healthy user effect, Mortality makecell, tabularx makecell, tabularx not-yet-known not-yet-known not-yet-known unknown Key Points Hip fracture mortality remains persistently high in older adults, and the perioperative benefit of statins remains a subject of debate. In this propensity score-matched study of 11,416 patients, pre-operative statin use was associated with a significant reduction in one-year all-cause mortality. However, this survival benefit was not accompanied by significant reductions in mechanistically related complications, such as stroke, cardiac arrest, venous thromboembolism, or sepsis. The dissociation between reduced mortality and unchanged complication rates suggests that the observed benefit may largely reflect the ”healthy user effect” rather than direct pharmacological protection. Findings support adhering to guidelines that recommend continuing statins in current users, but do not support initiating statin therapy solely to improve peri-operative survival in this population. not-yet-known not-yet-known not-yet-known unknown Plain Language Summary Hip fractures are a serious health concern for older adults, often leading to severe complications or death. Statins are widely used cholesterol-lowering drugs that also reduce inflammation, leading some experts to believe they might help patients recover better after surgery. We analyzed data from over 11,000 older patients undergoing hip fracture surgery to see if those taking statins had better outcomes than those who did not. We found that patients taking statins were significantly less likely to die within one year of their surgery. However, surprisingly, these patients did not have fewer strokes, heart problems, or infections compared to non-users. Since statins work by preventing these specific issues, we would expect these rates to drop if the drug were directly responsible for saving lives. Instead, our findings suggest that patients taking statins might simply be healthier overall or have better access to regular medical care—a phenomenon known as the ”healthy user effect.” Therefore, while patients already on statins should stay on them, our study suggests that doctors should not start prescribing them to new patients solely to improve survival after hip fracture surgery. not-yet-known not-yet-known not-yet-known unknown 1. Introduction Hip fracture in elderly patients represents a sentinel event associated with profound physiological vulnerability and persistently elevated mortality 1 . Despite substantial advances in surgical techniques, anesthetic management, and peri-operative care protocols, one-year mortality rates following hip fracture surgery remain approximately 20–25%, a figure that has shown limited improvement over recent decades 2,3 . Recent US population data confirm that hip fracture-related mortality declined modestly from 1999 to 2018 but has since plateaued 4 . This persistently high mortality underscores a critical clinical reality: successful osseous repair alone is insufficient to reverse the poor prognosis associated with hip fracture in older adults. Identifying modifiable factors and therapeutic interventions that can mitigate this excess mortality remains an urgent priority in geriatric orthopedic care. Mortality in this population is driven predominantly by systemic sequelae rather than the fracture itself. Major causes of death include cardiovascular collapse, pneumonia, venous thromboembolism (VTE), and sepsis 5,6 . A recent meta-analysis identified advanced age, higher American Society of Anesthesiologists (ASA) score, and pre-existing comorbidities as high-quality evidence predictors of early mortality 7 . The mechanical injury of hip fracture, compounded by subsequent surgical intervention, triggers a sustained inflammatory response characterized by elevated circulating concentrations of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha (TNF-α), accompanied by endothelial dysfunction and a pro-thrombotic state 8 . This hyper-inflammatory state distinguishes hip fracture from elective orthopedic procedures and creates a unique pathophysiological context in which immunomodulatory interventions may exert differential effects. Statins have garnered interest as potential peri-operative therapeutic agents owing to their pleiotropic effects that extend beyond lipid lowering 9 . Through inhibition of the mevalonate pathway, statins exert rapid-onset anti-inflammatory effects via nuclear factor-kappa B inhibition, resulting in reduced circulating concentrations of C-reactive protein and interleukin-6 within days of treatment initiation 10,11 . Furthermore, statins enhance endothelial nitric oxide synthase expression through inhibition of Rho GTPase signaling, potentially stabilizing endothelial function during periods of hemodynamic stress 11 . However, clinical evidence regarding peri-operative statin therapy remains conflicting. Large observational studies in non-cardiac surgery have reported protective associations with significant reductions in post-operative mortality 12 . In contrast, high-quality randomized controlled trials (RCTs) have frequently failed to replicate these benefits. The STICS trial in cardiac surgery demonstrated no reduction in post-operative atrial fibrillation, and the LOAD trial found no significant reduction in cardiovascular outcomes in statin-naïve patients undergoing non-cardiac surgery 13,14 . This discrepancy raises fundamental questions about whether the apparent protective association reflects true pharmacological benefit or residual confounding. A critical knowledge gap exists specifically in the hip fracture population. Unlike elective procedures, hip fracture surgery is urgent and performed on frail patients in an established catabolic state. Whether chronic statin therapy confers protection in this acutely compromised population, or whether observed associations merely reflect the superior baseline health of patients who adhere to preventive medications, remains an open question. This study aimed to evaluate the association between pre-operative statin use and post-operative outcomes in elderly patients undergoing hip fracture surgery, specifically examining whether any mortality reduction is accompanied by corresponding reductions in specific complications such as stroke, cardiac arrest, VTE, pneumonia, and sepsis. This analytical approach allows differentiation between potential pharmacological mechanisms and confounding by indication. 2. Methods makecell, tabularx makecell, tabularx 2.1. Data source This retrospective cohort study utilized data from the TriNetX US Collaborative Network, a federated health research network aggregating de-identified electronic health record (EHR) data from healthcare organizations across the United States. As of December 2025, the network included data from approximately 70 healthcare organizations. The platform provides patient-level data encompassing demographics, diagnoses, procedures, medications, and laboratory values. Due to the de-identified nature of the data, the Institutional Review Board waived the requirement for informed consent. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines 15 . not-yet-known not-yet-known not-yet-known unknown 2.2. Study population The study population comprised patients aged 65 to 85 years who underwent surgical intervention for hip fracture between January 1, 2013, and December 31, 2024. Diagnostic and procedural codes from the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), Current Procedural Terminology (CPT), and the Anatomical Therapeutic Chemical (ATC) classification system were used for cohort identification and outcome assessment (Online Resource 1). Patients were included if they had an index event defined as the co-occurrence of a hip fracture diagnosis (including fractures of the femoral head, neck, intertrochanteric region, or subtrochanteric region) and a qualifying surgical procedure (open reduction internal fixation, intramedullary nailing, hemiarthroplasty, or total hip arthroplasty) within a 30-day window. Patients were excluded if they had a history of pathological fractures, malignant neoplasms of bone, or congenital hip deformities. To distinguish between chronic statin users and non-users, patients with indeterminate exposure, defined as one or two statin prescription records within 3 months before surgery, were excluded. The remaining cohort was stratified into two groups based on preoperative statin status. The statin cohort comprised patients with at least three documented prescriptions or administrations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) within the 3 months preceding the index surgery. The control cohort consisted of patients with no record of statin use during the same preoperative period (Fig. 1). makecell, tabularx makecell, tabularx 2.3. Outcomes The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular and cerebrovascular events (stroke, cardiac arrest, and VTE) and infectious complications (pneumonia, sepsis, and post-operative infection). All outcomes were assessed at one-month, three-month, and one-year intervals following surgery. Patients were followed from the day after the index surgery until the occurrence of an outcome, death, or the end of the specified follow-up period. not-yet-known not-yet-known not-yet-known unknown 2.4. Statistical analysis Baseline characteristics included demographics, lifestyle factors, comorbidities, concomitant medications, and laboratory values. To minimize confounding by indication, 1:1 propensity score matching (PSM) was performed using a greedy nearest-neighbor algorithm based on all baseline covariates. Covariate balance was evaluated using standardized mean differences (SMDs), with values less than 0.1 indicating adequate balance 16. Kaplan-Meier methods were used to estimate survival probabilities, and the log-rank test was used to compare survival distributions. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was defined as a two-sided p-value less than 0.05. Subgroup analyses were performed by sex, age, and diabetes status. Sensitivity analyses were conducted by redefining the statin exposure window as prescription records within six months and twelve months before the index surgery. All analyses were conducted within the TriNetX Analytics Platform. makecell, tabularx makecell, tabularx 3. Results 3.1. Patient characteristics The initial query identified 31,944 eligible patients: 6,361 in the statin cohort and 25,583 in the control cohort. Before matching, the statin cohort had a significantly higher prevalence of hypertension, diabetes mellitus, and ischemic heart disease (p < 0.001). Following 1:1 PSM, 5,708 patients remained in each cohort. Baseline characteristics were well balanced, with SMDs less than 0.1 for all covariates (Online Resource 2). The matched population had a mean age of 76 years, and 63.9% were female. not-yet-known not-yet-known not-yet-known unknown 3.2. Primary outcome: All-cause mortality Pre-operative statin use was associated with a lower risk of all-cause mortality at all assessed time points (Table 1). At one-year follow-up, the mortality rate was 9.1% (n = 520) in the statin cohort compared to 12.3% (n = 700) in the control cohort (HR 0.723; 95% CI 0.645–0.810; p < 0.001). This association was also observed at one month (HR 0.623; p < 0.001) and three months (HR 0.705; p < 0.001). Kaplan-Meier analysis demonstrated a clear separation in survival probability favoring the statin cohort throughout the follow-up period (Fig. 2). 3.3. Secondary outcomes At one-year follow-up, no statistically significant differences were observed between cohorts for any secondary outcome (Table 1). The risks of stroke (2.5% vs. 2.1%; HR 1.143; p = 0.296), cardiac arrest (1.0% vs. 1.0%; HR 1.030; p = 0.875), and VTE (3.9% vs. 3.5%; HR 1.092; p = 0.381) were similar. Likewise, the incidence of pneumonia (5.5% vs. 5.0%; HR 1.088; p = 0.330), sepsis (5.4% vs. 5.0%; HR 1.069; p = 0.428), and post-operative infection (1.7% vs. 1.5%; HR 1.152; p = 0.339) was comparable. These findings were consistent across the one-month and three-month intervals. 3.4. Subgroup and sensitivity analyses Subgroup analyses demonstrated that the association between statin use and reduced all-cause mortality was consistent across sex, age, and diabetes status (Table 2). The mortality reduction was observed in both males (HR 0.747) and females (HR 0.721). Sensitivity analyses using six- and twelve-month exposure definitions yielded consistent results for the primary outcome (Online Resource 3). The six-month exposure analysis identified a statistically significant association with stroke risk (HR 1.279; p = 0.042), which was not observed in the three-month or 12-month analyses. makecell, tabularx makecell, tabularx 4. Discussion In this study, we evaluated the association between pre-operative statin use and post-operative outcomes in elderly hip fracture patients. Our primary finding was that statin use was associated with a significantly reduced one-year mortality (HR 0.723). However, this distinct survival benefit occurred in the absence of significant reductions in stroke, cardiac arrest, VTE, pneumonia, or sepsis. This pattern presents a fundamental interpretive challenge, as the mortality reduction lacks a mechanistic coherence through the measured clinical endpoints. If statins were conferring protection through their established pleiotropic effects, such as anti-inflammatory or endothelial stabilizing properties, we would theoretically expect corresponding reductions in at least some of the specific complications that contribute to post-fracture mortality. The absence of such signals suggests that unmeasured confounding, rather than direct pharmacological protection, remains the most likely explanation for the observed survival association. A plausible explanation for this dissociation is the ’healthy user effect’, a well-characterized form of confounding in pharmaco-epidemiologic research whereby patients who receive and adhere to preventive medications differ systematically from non-users in ways that independently predict better outcomes 17 . Statin users typically demonstrate superior adherence to other preventive health services, including cancer screening, vaccinations, and regular physician visits, behaviors that serve as markers of general health consciousness rather than reflecting direct effects of therapy 18 . Furthermore, previous studies have shown that statin users often exhibit lower rates of adverse outcomes that lack biological plausibility for statin protection, such as reduced accident risk 19,20 . In our study population, the requirement for multiple statin prescriptions within the exposure window inherently selected for highly adherent patients. This selection criterion may have amplified the healthy user bias by filtering for patients with higher functional status and cognitive engagement, traits that are strongly protective against mortality but are not captured in administrative datasets. The magnitude of confounding from medication adherence should not be underestimated. Notably, a comprehensive meta-analysis of medication adherence studies demonstrated that adherence to placebo was associated with substantially reduced mortality (pooled odds ratio 0.56) 21 . This effect size is remarkably similar to the mortality reduction often attributed to statins in observational studies and is nearly identical to the hazard ratio of 0.72 observed in our cohort. This implies that adherence behavior itself, independent of any pharmacological action, serves as a powerful proxy for superior physiological reserve and social support. Although propensity score matching balanced the measured comorbidities and demographics, it fundamentally cannot account for unmeasured domains such as frailty, functional independence, and socio-economic resources, all of which act as silent confounders influencing post-fracture survival 22 . We also evaluated the ’severity attenuation hypothesis’, which posits that statins might not prevent the occurrence of complications but rather attenuate their severity, enabling patients to survive events that would otherwise prove fatal. Under this framework, statin users might experience similar rates of pneumonia or sepsis but with reduced organ dysfunction and improved recovery trajectories. While statins have indeed demonstrated immunomodulatory effects in infectious contexts, such as modulating cytokine production and inflammatory cell activation, this hypothesis would predict that the mortality benefit should be concentrated specifically among patients who develop these complications 23,24 . However, the complete absence of even non-significant favorable trends in the incidence of any measured complication diminishes the plausibility of this mechanism as the primary driver of the 28% reduction in mortality. Regarding secondary outcomes, the finding of increased stroke risk in the six-month exposure sensitivity analysis (HR 1.279, p = 0.042) warrants cautious interpretation. Statin withdrawal has been associated with endothelial dysfunction through suppression of nitric oxide production and rebound activation of Rho GTPase signaling 25,26 . Clinical evidence from acute coronary syndrome patients has shown that statin discontinuation can significantly increase cardiovascular event rates 27,28 . However, critically, this stroke signal appeared only in the six-month exposure cohort and was absent in the 12-month analysis (HR 1.153, p = 0.200). If peri-operative statin withdrawal were the primary mechanism, patients with longer exposure duration might be expected to demonstrate equal or greater risk due to established physiological dependence. The inconsistency across exposure windows raises the possibility that the six-month finding represents statistical noise from multiple comparisons or captures a distinct sub-population with inherently unstable cardiovascular status, rather than a definitive biological effect. Crucially, our observed mortality reduction exceeds the effect sizes reported in RCTs of peri-operative statins, which have generally shown null results. For instance, the STICS trial in cardiac surgery and the LOAD trial in non-cardiac surgery failed to demonstrate the survival benefits frequently seen in observational data 13,14 . This discrepancy is informative: when observational studies consistently demonstrate larger protective effects than RCTs of the same intervention, residual confounding is the most parsimonious explanation. The 2024 AHA/ACC Guideline for Perioperative Cardiovascular Management recommends continuation of statins in patients already receiving them but does not recommend initiation in statin-naïve patients, a position consistent with our data suggesting that observed benefits likely reflect patient selection rather than drug efficacy 29 . Our findings must be interpreted in the context of several limitations. First, the TriNetX platform, while providing access to a large, geographically diverse population, relies on administrative and electronic health record data. Consequently, it lacks clinical granularity regarding key prognostic factors such as frailty scores and functional status. Second, our exposure definition based on outpatient prescriptions cannot confirm actual medication ingestion or capture in-hospital administration. Third, the absence of cause-specific mortality data prevents determination of whether the mortality reduction occurred specifically in cardiovascular deaths, which would be more biologically consistent with statin mechanisms. Finally, despite robust propensity score matching, unmeasured confounding remains a significant limitation inherent to this study design. 5. Conclusion Pre-operative statin use was associated with significantly reduced one-year mortality in elderly hip fracture patients; however, this benefit was not accompanied by reductions in stroke, cardiac arrest, VTE, pneumonia, or sepsis. This dissociation, combined with effect sizes exceeding those of RCTs, suggests that chronic statin use likely serves as a marker of superior physiological reserve (the healthy user effect) rather than conferring direct pharmacological protection in the peri-operative setting. While adherence to guidelines recommending statin continuation remains appropriate, our findings do not support initiating statins in statin-naïve elderly patients solely to improve hip fracture outcomes. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. makecell, tabularx makecell, tabularx References 1. Koso RE, Sheets C, Richardson WJ, Galanos AN. Hip Fracture in the Elderly Patients: A Sentinel Event. Am J Hosp Palliat Care . Apr 2018;35(4):612–619. doi:10.1177/10499091177250572. Haentjens P, Magaziner J, Colon-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med . 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Nov 5 2024;84(19):1869–1969. doi:10.1016/j.jacc.2024.06.013 makecell, tabularx makecell, tabularx 1 month follow-up All-cause mortality 129 (2.3%) 204 (3.6%) 0.623 (0.500, 0.777) < 0.001 Stroke 38 (0.7%) 38 (0.7%) 0.991 (0.632, 1.553) 0.968 Cardiac arrest 20 (0.4%) 19 (0.3%) 1.040 (0.555, 1.949) 0.902 Venous thromboembolism 82 (1.5%) 79 (1.5%) 1.022 (0.750, 1.392) 0.889 Pneumonia 104 (2.0%) 81 (1.6%) 1.227 (0.918, 1.641) 0.166 Sepsis 94 (1.7%) 87 (1.6%) 1.041 (0.777, 1.393) 0.789 Infection 43 (0.8%) 40 (0.7%) 1.055 (0.686, 1.623) 0.806 3 months follow-up All-cause mortality 273 (4.8%) 380 (6.7%) 0.705 (0.603, 0.823) < 0.001 Stroke 70 (1.3%) 54 (1.0%) 1.280 (0.898, 1.826) 0.171 Cardiac arrest 34 (0.6%) 30 (0.5%) 1.116 (0.683, 1.823) 0.661 Venous thromboembolism 144 (2.7%) 139 (2.6%) 1.018 (0.807, 1.286) 0.878 Pneumonia 167 (3.2%) 144 (2.8%) 1.106 (0.885, 1.382) 0.375 Sepsis 162 (3.0%) 160 (3.0%) 0.973 (0.782, 1.210) 0.805 Infection 76 (1.3%) 71 (1.3%) 1.049 (0.759, 1.450) 0.77 1 year follow-up All-cause mortality 520 (9.1%) 700 (12.3%) 0.723 (0.645, 0.810) < 0.001 Stroke 132 (2.5%) 113 (2.1%) 1.143 (0.889, 1.469) 0.296 Cardiac arrest 57 (1.0%) 54 (1.0%) 1.030 (0.710, 1.495) 0.875 Venous thromboembolism 209 (3.9%) 187 (3.5%) 1.092 (0.897, 1.330) 0.381 Pneumonia 289 (5.5%) 251 (5.0%) 1.088 (0.918, 1.288) 0.33 Sepsis 296 (5.4%) 264 (5.0%) 1.069 (0.906, 1.262) 0.428 Infection 99 (1.7%) 84 (1.5%) 1.152 (0.861, 1.541) 0.339 makecell, tabularx makecell, tabularx Table 1. Kaplan-Meier analysis of clinical outcomes between statin exposure and control cohorts stratified by follow-up intervals. The analysis includes outcomes assessed at 1 month, 3 months, and 1 year after the index surgery. Abbreviations: CI, confidence interval All-cause mortality Sex Male 226 (11.7%) 293 (15.2%) 0.747 (0.628, 0.888) 0.001 Female 274 (7.6%) 372 (10.4%) 0.721 (0.617, 0.843) < 0.001 Age (year) 65-75 169 (6.9%) 234 (9.5%) 0.709 (0.582, 0.865) 0.001 75-85 362 (10.4%) 471 (13.6%) 0.749 (0.653, 0.859) < 0.001 DM With DM 237 (10.3%) 279 (12.2%) 0.836 (0.703, 0.994) 0.042 Without DM 275 (8.2%) 370 (11.1%) 0.735 (0.629, 0.859) < 0.001 Stroke Sex Male 52 (2.9%) 46 (2.6%) 1.099 (0.739, 1.634) 0.641 Female 78 (2.3%) 64 (1.9%) 1.206 (0.867, 1.679) 0.266 Age (year) 65-75 54 (2.4%) 49 (2.1%) 1.104 (0.750, 1.625) 0.615 75-85 78 (2.4%) 66 (2.1%) 1.152 (0.830, 1.599) 0.398 DM With DM 74 (3.5%) 70 (3.3%) 1.051 (0.758, 1.457) 0.767 Without DM 60 (1.9%) 49 (1.6%) 1.221 (0.837, 1.780) 0.299 Cardiac arrest Sex Male 21 (1.1%) 24 (1.2%) 0.850 (0.473, 1.527) 0.586 Female 31 (0.9%) 29 (0.8%) 1.048 (0.632, 1.739) 0.855 Age (year) 65-75 29 (1.2%) 25 (1.0%) 1.145 (0.670, 1.954) 0.621 75-85 28 (0.8%) 28 (0.8%) 0.976 (0.578, 1.648) 0.928 DM With DM 31 (1.4%) 32 (1.4%) 0.955 (0.583, 1.565) 0.855 Without DM 27 (0.8%) 20 (0.6%) 1.340 (0.751, 2.389) 0.32 Venous thromboembolism Sex Male 77 (4.2%) 63 (3.5%) 1.189 (0.852, 1.658) 0.308 Female 129 (3.8%) 106 (3.1%) 1.189 (0.920, 1.538) 0.186 Age (year) 65-75 81 (3.5%) 79 (3.4%) 0.996 (0.730, 1.358) 0.979 75-85 131 (4.0%) 104 (3.2%) 1.232 (0.952, 1.593) 0.112 DM With DM 101 (4.6%) 78 (3.6%) 1.268 (0.944, 1.704) 0.114 Without DM 99 (3.1%) 100 (3.2%) 0.977 (0.740, 1.290) 0.87 Pneumonia Sex Male 123 (7.0%) 111 (6.5%) 1.050 (0.812, 1.357) 0.709 Female 150 (4.5%) 137 (4.3%) 1.031 (0.818, 1.300) 0.794 Age (year) 65-75 115 (5.1%) 100 (4.5%) 1.107 (0.846, 1.447) 0.459 75-85 183 (5.7%) 164 (5.3%) 1.049 (0.850, 1.295) 0.655 DM With DM 126 (6.0%) 122 (6.1%) 0.970 (0.756, 1.245) 0.812 Without DM 144 (4.7%) 138 (4.6%) 1.002 (0.793, 1.265) 0.989 Sepsis Sex Male 123 (6.7%) 120 (6.8%) 0.964 (0.750, 1.240) 0.775 Female 164 (4.7%) 152 (4.5%) 1.036 (0.831, 1.291) 0.755 Age (year) 65-75 115 (5.0%) 117 (5.2%) 0.946 (0.731, 1.224) 0.673 75-85 190 (5.7%) 187 (5.8%) 0.961 (0.785, 1.176) 0.697 DM With DM 153 (7.1%) 142 (6.9%) 1.011 (0.804, 1.270) 0.927 Without DM 145 (4.5%) 141 (4.5%) 0.997 (0.790, 1.257) 0.977 Infection Sex Male 34 (1.8%) 31 (1.6%) 1.061 (0.652, 1.727) 0.81 Female 67 (1.9%) 62 (1.7%) 1.065 (0.754, 1.504) 0.722 Age (year) 65-75 49 (2.0%) 51 (2.1%) 0.945 (0.638, 1.398) 0.776 75-85 54 (1.6%) 42 (1.2%) 1.255 (0.839, 1.879) 0.268 DM With DM 47 (2.1%) 39 (1.7%) 1.184 (0.775, 1.811) 0.434 Without DM 55 (1.6%) 44 (1.3%) 1.232 (0.829, 1.832) 0.301 Table 2. Subgroup analysis of the association between statin use and clinical outcomes at 1-year follow-up using Kaplan-Meier analysis. The analysis compares the Statin Exposure cohort vs. the Control cohort within each specific subgroup. Abbreviations: CI, confidence interval; DM, diabetes mellitus; not-yet-known not-yet-known not-yet-known unknown not-yet-known not-yet-known not-yet-known unknown Figure captions Figure 1. Flowchart of patient selection process from the TriNetX US collaborative network database. Figure 2. Kaplan-Meier analysis of overall survival between statin exposure and control cohorts stratified by follow-up intervals. The panels display the survival probability free from all-cause mortality at different follow-up periods: (a) 1-month, (b) 3-months, and (c) 1-year after the index surgery. Information & Authors Information Version history V1 Version 1 21 January 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords healthy user effect hip fracture mortality statin Authors Affiliations Ling Lee National Defense Medical University View all articles by this author Shu-Han Chuang Changhua Christian Hospital Department of Ophthalmology View all articles by this author Cheng-Hsien Chang Changhua Christian Hospital Department of Ophthalmology View all articles by this author Yi-Jie Kuo Taipei Medical University View all articles by this author Lien-Chen Wu Taipei Medical University View all articles by this author Yu-Zhi Lian Taipei Medical University School of Nutrition and Health Sciences View all articles by this author Yu-Pin Chen 0000-0002-9729-6375 [email protected] Taipei Medical University View all articles by this author Metrics & Citations Metrics Article Usage 161 views 54 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ling Lee, Shu-Han Chuang, Cheng-Hsien Chang, et al. 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