Hydrophilic Statin Use Research Articles

Association of venous thromboembolism between hydrophilic and lipophilic statin users among diabetic subjects.

This retrospective analysis aimed to compare the risk of venous thromboembolism (VTE) between patients with diabetes mellitus who received hydrophilic statin treatment to those who receive lipophilic statin. There were 6639 patients receiving hydrophilic statin therapy and 10,854 patients receiving lipophilic statin therapy in the study. The hazard ratios and 95% confidence intervals for VTE were estimated using univariate and multivariate Cox proportional hazards models when the study cohorts were compared. Among all patients, the incidence rate of VTE was 4.27 per 1000 person-years in the control cohort, 4.18 per 1000 person-years in the hydrophilic statin use cohort, and 3.91 per 1000 person-years in the lipophilic statin use cohort. After adjusting for age, sex, and comorbidities, the risk of VTE in the hydrophilic statin use cohort was 0.90 (0.72, 1.12) lower than that in the control cohort, the risk of VTE in the lipophilic statin use cohort was 0.87 (0.72, 1.05) lower than that in the control cohort, and the risk of VTE in the lipophilic statin use cohort was 0.97 (0.78, 1.21) lower than that in the hydrophilic statin use cohort. However, all were not statistically significant. Our result showed that there was no significant difference among the study cohorts regarding the outcome of VTE.

Statin Prescription Patterns and Associations with Subclinical Inflammation.

Background and Objectives: Statins have been extensively utilised in atherosclerotic cardiovascular disease (ASCVD) prevention and can inhibit inflammation. However, the association between statin therapy, subclinical inflammation and associated health outcomes is poorly understood in the primary care setting. Materials and Methods: Primary care electronic health record (EHR) data from the electronic Practice-Based Research Network (ePBRN) from 2012–2019 was used to assess statin usage and adherence in South-Western Sydney (SWS), Australia. Independent determinants of elevated C-reactive protein (CRP) were determined. The relationship between baseline CRP levels and hospitalisation rates at 12 months was investigated. Results: The prevalence of lipid-lowering medications was 14.0% in all adults and 44.6% in the elderly (≥65 years). The prevalence increased from 2012 to 2019 despite a drop in statin use between 2013–2015. A total of 55% of individuals had good adherence (>80%). Hydrophilic statin use and higher intensity statin therapy were associated with elevated CRP levels. However, elevated CRP levels were not associated with all-cause or ASCVD hospitalisations after adjusting for confounders. Conclusions: The prevalence and adherence patterns associated with lipid-lowering medications highlighted the elevated ASCVD-related burden in the SWS population, especially when compared with the Australian general population. Patients in SWS may benefit from enhanced screening protocols, targeted health literacy and promotion campaigns, and timely incorporation of evidence into ASCVD clinical guidelines. This study, which used EHR data, did not support the use of CRP as an independent marker of future short-term hospitalisations.

Incident Rheumatoid Arthritis Following Statin Use: From the View of a National Cohort Study in Korea.

Safety issues regarding the potential risk of statins and incident rheumatoid arthritis (RA) have been raised, but the existing data are largely based on Caucasian populations, and continue to have biases and require further validation in Asian populations. Here, we aimed to verify the risk of RA depending on the duration of previous statin use and statin types using a large-scale, nationwide database. This study enrolled 3149 patients with RA and 12,596 matched non-RA participants from the national health insurance database (2002–2015), and investigated their statin prescription histories for two years before the index date. Propensity score overlap-weighted logistic regression was applied after adjusting for multiple covariates. The prior use of any statins and, specifically, the long-term use of lipophilic statins (>365 days) were related to a lower likelihood of developing RA ((odds ratio (OR) = 0.73; 95% confidence intervals (CI) = 0.63–0.85, p < 0.001) and (OR = 0.71; 95% CI = 0.61–0.84, p < 0.001), respectively). Subgroup analyses supported these preventive effects on RA in those with dyslipidemia, independent of sex, age, smoking, alcohol use, hypertension, and hyperglycemia. Hydrophilic statin use or short-term use showed no such associations. Our study suggests that prior statin use, especially long-term lipophilic statin use, appears to confer preventive benefits against RA.

Association between Statin Use and Gastric Cancer: A Nested Case-Control Study Using a National Health Screening Cohort in Korea.

Concerns about the hazards of statins on the development and mortality of stomach cancers remain controversial. Here, we investigated the likelihood of incident gastric cancers and related mortality depending on statin exposure, statin type, and the duration of use. This nested case–control-designed study was composed of 8798 patients who were diagnosed with gastric cancer and matched with 35,192 controls at a 1:4 ratio based on propensity scores of age, sex, residential area, and income from the Korean National Health Insurance Service—Health Screening Cohort database (2002–2015). Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior use of statins (any statin, hydrophilic statins vs. lipophilic statins) with incident gastric cancer and its mortality depending on the medication duration (<180 days, 180–545 days, and >545 days) after adjusting for multiple covariates. After adjustment, the use of any statin, hydrophilic statins, or lipophilic statins showed significant associations with lower odds for incident stomach cancer when used for a short-term period (180–545 days) (OR = 0.88, 95% CI = 0.81–0.86, p = 0.002; OR = 0.78, 95% CI = 0.66–0.92, p = 0.004; and OR = 0.91, 95% CI = 0.84–0.99, p = 0.039, respectively) compared to the control group. Hydrophilic statin use for 180–545 days was associated with 53% lower overall mortality (OR = 0.47; 95% CI = 0.29–0.77). In subgroup analyses, beneficial effects on both cancer development and mortality persisted in patients ≥65 years old, patients with normal blood pressure, and patients with high fasting glucose levels. There were no such associations with long-term statin use (>545 days). Thus, the current nationwide cohort study suggests that prior short-term statin use may have anti-gastric cancer benefits in elderly patients with hyperglycemia.

Statin Type and Cancer Outcomes in Patients with Diabetes Type 2 and Solid Tumors.

Objective:Type 2 diabetes mellitus (T2DM) affects 10% of Americans and is associated with an increased incidence of cancer. Statins are first-line cholesterol-lowering medications in the treatment of hyperlipidemia. Several studies have demonstrated a relationship between statin use and reduced cancer incidence. We examined the cancer benefits of statin subtypes, with specific attention to disease-free survival (DFS) and overall survival (OS).Methods:This retrospective review included adults with T2DM diagnosed with solid tumors at Roswell Park Cancer Institute in Buffalo, NY, USA (2003–2010). Individuals with gestational diabetes, incomplete records, or diagnosed with rare solid tumors were excluded. Follow-up began at the date of diagnosis and ended with the first confirmed recurrence, death, or loss of contact. Demographics were assessed by Chi-square, Kaplan–Meier survival analyses, and Cox proportional hazards regression.Findings:Overall, 1102 patients met inclusion criteria, 52.1% of the study participants were female, and 578 participants (52.5%) died during the follow-up period which ranged from 0 to 156 months. Hydrophilic statin use was associated with improved DFS at 5-year follow-up (41.0% vs. 36.9%, P = 0.0077) compared to lipophilic statin use. Multivariate regression revealed that hydrophilic statins were associated with improved DFS (hazard ratio [HR]: 0.706, 95% confidence interval [CI]: 0.526–0.947) and OS (HR: 0.685, 95% CI: 0.503–0.934). Pravastatin was associated with improved OS (HR: 0.674, 95% CI: 0.471–0.964).Conclusion:In patients with T2DM and cancer, hydrophilic statins, and pravastatin in particular, are associated with improved DFS as well as OS. Further research examining the cancer-specific effects of hydrophilic and lipophilic statins is needed to better understand their beneficial effects.

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population.

Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Prospective propensity score (PS)-matched cohort. Swedish registers, 2005 to 2013. A PS-matched cohort of 16668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63279 eligible adults. Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users. Lack of lipid, fibrosis, or HCC surveillance data. In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. None.

The Different Cardiovascular Outcomes Between Long-Term Efficacy of Hydrophilic and Lipophilic Statin Therapy in Both Asian Diabetic Sexes.

Purpose:To evaluate the long-term efficacy of hydrophilic and lipophilic statin therapy for cardiovascular outcomes in Asian diabetic patients.Method:Newly diagnosed cases of type 2 diabetes during the period from January 2000 to December 2011 were divided into 2 cohorts on the basis of their statin use, namely hydrophilic statin and lipophilic statin. We used Cox proportional hazard regression models to analyze the risks of cardiovascular outcomes.Result:In this study, 12 896 patients used statin, including 4259 patients using hydrophilic statin and 8637 patients using lipophilic statin. With 12-year follow-up, higher incidence rate of coronary artery disease and stroke was noted in the lipophilic statin use instead of hydrophilic statin use.Conclusion:According to our long-term cohort study, hydrophilic statin use may be a better choice than lipophilic statin to reduce cardiovascular events in Asian diabetic patients.

Comparative risk of lipophilic and hydrophilic statins on incident depression: A retrospective cohort study

ObjectivesTo evaluate the risk of new-onset depression in a cohort of US adult patients initiating lipophilic statin therapy compared to hydrophilic statin therapy. DesignRetrospective cohort study. SettingLarge US commercial claims database Participants1:1 propensity score matched cohort of lipophilic (atorvastatin, lovastatin and simvastatin) and hydrophilic (pravastatin and rosuvastatin) statin initiators between January 2009 to June 2015. OutcomeNew onset of depression. ResultsIn a propensity-score matched cohort of 299,298 statin initiators, the crude incidence of depression in the hydrophilic and lipophilic group was 136.6 and 142.8 per 10,000 person-years respectively. Compared to hydrophilic statin use, lipophilic statin use was not associated with a statistically significant increase in the risk of depression, adjusted HR 1.05 (95% CI, 1.00–1.10, p = 0.078) and excess incidence of 6.3 (95% CI, -0.7–13.7) per 10,000 person-years. Findings were consistent across the subgroups of patients with history of psychiatric conditions HR 1.05 (95% CI, 0.94–1.16, p = 0.41), and those initiating statins for primary or secondary prevention, HR 1.03 (95% CI, 0.97–1.10, p = 0.33) and 1.07 (95% CI, 0.99–1.16, p = 0.10) respectively. Within individual lipophilic statins, only simvastatin was associated with a moderate increase in the risk of depression HR 1.09 (95% CI, 1.02–1.16, p = 0.003), followed by lovastatin HR 1.07 (95% CI, 0.93–1.24, p = 0.34) and atorvastatin HR 1.05 (95% CI, 0.97–1.13, p = 0.27). LimitationsFindings are generalizable to patients with commercial insurance. ConclusionsLipophilic statin use was not associated with a significant increase in the risk of incident depression.

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis.

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2) = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2) = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2) = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.

Abstract PD1-01: Impact of statin use on cancer recurrence and mortality in patients with breast cancer: A systematic review and meta-analysis

Abstract Background: Statins have been described as having an association with a decreased risk of breast cancer. They have also shown antineoplastic properties in preclinical studies. Statins inhibit the enzyme 'HMG CoA reductase' and the expression of this enzyme in cancer cells has been implicated as an adverse prognostic factor in patients with breast cancer. Methods: We performed a systemic review of literature through April 2015 and utilized PubMed and Embase to identify studies that described an association between statin use and survival in breast cancer. Studies which did not report a comparison of survival using Kaplan-Meier curves were excluded. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated using the random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: After reviewing 637 abstracts, 12 studies which included a total of 87951 patients were identified and data was extracted. 8 studies provided a summary statistic for the association of statins with recurrence-free survival (RFS) in patients with breast cancer and were included in a meta-analysis. Statin use was associated with improved RFS (N= 29729 patients, HR 0.66; 95% CI 0.53- 0.84) with moderate heterogeneity (I2= 48%). Furthermore, this survival benefit appeared to be confined to use of lipophilic statins (3 studies, HR 0.72; 95% CI 0.59- 0.89) as hydrophilic statin use was not associated with improvement in RFS (3 studies, HR 0.80; 95% CI 0.44- 1.46). A meta-analysis of 5 studies showed no significant association between the use of statins on breast cancer-specific survival (CSS) (N= 60686 patients, HR 0.71; 95% CI 0.49- 1.03, I2= 84%). We also found no association between statin use and overall survival (OS) (5 studies and 22283 patients, HR 0.83; 95% CI 0.58- 1.19, I2= 62%). Conclusions: Statin use, or more specifically, lipophilic statin use is associated with an improved recurrence-free survival for patients with breast cancer. However, there was no effect of statin use on either cancer-specific survival or overall survival. These benefits need to be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs will need to be identified. Characteristics of included studiesNameYearCountryImpact on RFSImpact on CSSImpact on OSSample SizeMedian follow-up (in years)Desai2015USANA0.59 [0.32, 1.06]NA7,88311.5Cardwell2015UKNA0.84 [0.68, 1.04]0.84 [0.72, 0.97]17,8805.7Murtola2014FinlandNA0.46 [0.38, 0.55]NA31,1143.25Boudreau2014USA0.78 [0.56, 1.08]NANA4,2166.3Sendur2014TurkeyP 0.004P 0.005P = 0.0051,1724Brewer2013USA0.49 [0.28-0.84]0.85 [0.46, 1.57]0.80 [0.43, 1.49]724NANickels2013Germany0.83 [0.54,1.24]0.89 [0.52, 1.49]1.21 [0.87, 1.69]3,085*5.3Zeichner2013USA1.42 [0.42, 4.81]NA1.5 [0.07, 32.02]3003.5Chae2011USA0.40 [0.24, 0.67]NANA7034.5Ceacareanu2011USA0.27 [0.10, 0.71]NA0.23 [0.08, 0.66]2942.5Ahern2011Denmark0.80 [0.64, 1.00]NANA18,7696.8Kwan2008USA0.67 [0.39, 1.13]NANA1,8115*= sample size for RFS: 2912, Abbreviations: RFS: recurrence-free survival, CSS: cancer-specific survival, OS: overall survival (expressed in hazard ratio and 95% confidence intervals) Citation Format: Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in patients with breast cancer: A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-01.

Statins: do they have a potential role in cancer prevention and modifying cancer-related outcomes?

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are currently among the most commonly prescribed pharmaceutical agents worldwide. Apart from their well-established therapeutic value in cardiovascular disease, there is a long-standing debate on their potential association with cancer. To obtain and discuss the existing clinical evidence, an overview of meta-analysis articles addressing this issue was carried out. As of today, the accumulated evidence does not support the hypothesis that statins affect the risk of developing cancer, when they are taken at low doses for managing hypercholesterolaemia. However, current data cannot exclude an increased cancer risk in elderly patients associated with hydrophilic statin use, or decreases in the risks of certain cancers, such as gastric, oesophageal, liver, colorectal and advanced/aggressive prostate cancer. On the other hand, some recent observational studies have provided evidence that statins might be useful in modifying the prognosis of patients diagnosed with malignancy. Until a definitive benefit is demonstrated in randomized controlled trials, statins cannot be recommended either for cancer prevention or for modifying cancer-related outcomes. Further research is warranted to clarify the potential role(s) of statins in the prevention and treatment of cancer.

Abstract 2173: Survival time in pancreatic cancer patients with metabolic syndrome varies by use of insulin and statins

Abstract Background: Insulin-sensitizing drugs (i.e. metformin) and lipid-lowering agents (i.e. statins) demonstrate pleiotropic effects against cancer cell lines and show potential as therapeutic adjuvants for cancer patients. Our objective was to examine the association of specific classes of diabetes drugs and statins on survival time among pancreatic cancer patients with metabolic syndrome. Methods: Linked Surveillance, Epidemiology and End Results (SEER) cancer registry and Medicare claims data were used identify pancreatic cancer patients diagnosed in 2008-2009 with the following: resection of the pancreas, metabolic syndrome prior to cancer diagnosis, continual enrollment in Medicare Parts A, B, and D. Metabolic syndrome was defined as having 3 out of the 4 conditions: hyperglycemia, dyslipidemia, obesity, or hypertension. Exposure to diabetes drugs and statins 12 months prior to resection of cancer was assessed in the prescription drug event database and categorized as insulin/sulfonylureas vs. metformin/thiazolidinediones (TZD) vs. none; and as no statin vs. lipophilic statin vs. hydrophilic statin. We employed Cox regression adjusting for age, sex, race, stage at diagnosis and chemotherapy, to estimate the impact of individual drug classes on survival with pancreatic cancer. Results: We analyzed data on 263 pancreatic cancer cases with metabolic syndrome. Users of insulin/sulfonylureas demonstrated shorter survival by 6 months and had higher hazard of death (HR=1.43, 95%CI (1.05, 1.95)) compared to non-users. In contrast, users of hydrophilic statins experienced longer survival by 9 months and showed lower hazard of death compared to those who did not use statin (HR = 0.67, 95%CI (0.46, 0.96)) (Table). Conclusion : Insulin/sulfonylureas use is associated with shorter survival, while hydrophilic statin use was associated with longer survival in pancreatic patients with metabolic syndrome. Table. Relative hazard of death in pancreatic cancer patients by diabetes drugs and statin VariablesCategorynMedian survival (months, 95%)unadjusted HR (95%)adjusted HR* (95%)P-valueDiabetes medications administered prior to cancer diagnosisNo insulin/sulfonylurea/metformin/TZD13120.2 (15.6, 25.0)RefRefMetformin/TZD2721.7 (10.5, NA)0.73 (0.43, 1.24)0.80 (0.50, 1.39)0.42Insulin/sulfonylurea10513.9 (9.4, 21.2)1.29 (0.96, 1.73)1.43 (1.05, 1.95)0.02Statins administered prior to cancer diagnosisNo statin10614.6 (10.7, 18.3)RefRefLipophilic statins8320.8 (14.9, 28.6)0.76 (0.55, 1.06)0.72 (0.51, 1.02)0.07Hydrophilic statins7423.5 (17.8, 31.0)0.63 (0.44, 0.90)0.67 (0.46, 0.96)0.03*Adjusted for age, sex, race, stage and chemotherapy Citation Format: Christie Y. Jeon, Stephen J. Pandol, Marc T. Goodman. Survival time in pancreatic cancer patients with metabolic syndrome varies by use of insulin and statins. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2173. doi:10.1158/1538-7445.AM2014-2173

Prospective Analysis Of Statin Use and Risk Of Non-Hodgkin's Lymphoma In The Women's Health Initiative Cohort

IntroductionHMG CoA reductase inhibitors (statins) are a class of cholesterol lowering drugs that affect many intracellular pathways and have implications for cancer chemo prevention. Statins have been shown to induce a phosphoprotein signature that shuts MYC activation and also have anti-inflammatory activity that may impact the risk of Non-Hodgkin's lymphoma (NHL). Results from observational studies on the relationship between statin use and NHL are conflicting. We analyzed data from the Women's Health Initiative (WHI) to assess the relationship between statins and the risk of NHL. MethodsThe study population included 161,563 post-menopausal women ages 50-79 years. Women with incident NHL were identified over an average of 10.8 (SD +3.3) years of follow-up. Information on statin use was collected at study entry and at years 1, 3, 6 and 9. Statins were classified as lipophilic (simvastatin, lovastatin, fluvastatin) or hydrophilic (pravastatin, atorvastatin) by potency (low, medium, high) and by duration of use. Self and interviewer-administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the relationship between statin use and NHL risk as a time-dependent exposure. Multivariable models were stratified by WHI trial, extension study and age group and were adjusted for education, ethnicity, smoking, alcohol, body mass index, waist circumference, % energy from fat, hormone therapy use, physical activity, current medical provider and history of lupus and rheumatoid arthritis. A separate analysis was performed for individual NHL subtypes: Diffuse Large B cell Lymphoma (DLBCL) (n=228), follicular lymphoma (n=169) and Small Lymphocytic Lymphoma/Chronic Lymphocytic Lymphoma (SLL/CLL) (n=74).All statistical tests were two-sided. ResultsStatins were used at baseline by 12,243 women (7.5%), 8266 of whom used lipophilic agents. The multivariable adjusted HR of overall statin use and risk of NHL was 0.66 (95% CI: 0.48-0.90). Hydrophilic statin use was associated with a significantly lower risk of developing NHL (HR 0.47, 95% C.I. 0.27-0.81); HR for pravastatin 0.46 (95% C.I. 0.20-1.02) and for atorvastatin 0.39 (95% C.I. 0.124-1.20). Lipophilic statins were not associated with NHL risk (HR 0.85, 95% C.I. 0.58-1.24). Among NHL subtypes, statin use was associated with a lower risk of DLBCL (HR 0.49, 95% C.I. 0.25-0.96) however there was no association with follicular lymphoma (HR 0.92, 95% C.I. 0.49-1.70) or CLL/SLL (HR 1.18, 95% C.I. 0.50-2.75). ConclusionPrior use of statins was associated with a lower overall risk of NHL attributable to a lower risk of DLBCL in the WHI cohort. This effect was largely seen among users of hydrophilic statins. Disclosures:Safford:Amgen: Research Funding.

Abstract PD03-08: Statin use and improved outcome in primary inflammatory breast cancer: retrospective cohort study

Abstract Background Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer. HMG-CoA reductase inhibitors (statins) are cholesterol reducing agents with pleiotropic effects, including antitumorigenic and anti-inflammatory properties. We hypothesized that statins reduce the metastatic potential in primary IBC. Methods We retrospectively reviewed 724 patients diagnosed with and treated for primary IBC at The University of Texas MD Anderson Cancer Center between Jan. 12, 1995 and Jan. 27, 2011. Patients with records indicating statin use at the time of IBC diagnosis on the electronic medical record were compared with those without. We further compared outcomes stratified by statin type (hydrophilic [H] versus lipophilic [L]). We used the Kaplan-Meier method to estimate the median disease-free survival (DFS) after surgery, overall survival (OS), and disease specific survival (DSS), followed by Cox proportional hazards regression model to test statistical significance of several potential prognostic factors. Results For primary IBC patients who had information on their statin use status at IBC diagnosis, the median DFS time were 4.88 years, 2.47 years and 1.76 years (P= 0.04); the median OS time 5.05 years, 3.79 years and 4.32 years (P= 0.35); and the median DSS time 5.10 years, 3.79 years and 4.52 years (P= 0.37), for patients who took “ H”, “L” and no statin, respectively. In multivariable Cox model stratified by radiation therapy, ER/PR status and HER2 status, statin “H” use was associated with significantly improved DFS compared to no statin use (HR=0.49; 95% CI: 0.28–0.84; p&amp;lt;0.01), adjusted for lymphatic/vascular invasion. Although there is a trend that patients who used statin “H” had a longer time to death compared to patients who did not take statin, it did not reach statistical significance for OS (HR=0.80; 95% CI: 0.43–1.49; p=0.49) and DSS (HR=0.85; 95% CI: 0.46–1.57, p=0.59) after adjustment for lymphatic/vascular invasion, nuclear grade and surgery status within one year. Conclusions Hydrophilic statin use was associated with improved DFS. There was a trend for reduced HR in OS and DSS among primary IBC patient who used hydrophilic statins. A prospective randomized study to evaluate the potential survival benefits of statins in primary IBC population is warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD03-08.

Statin Prescriptions and Breast Cancer Recurrence Risk: A Danish Nationwide Prospective Cohort Study

Accumulating evidence suggests that statins affect diseases other than cardiovascular disease, including cancer, and that these effects may depend on the lipid solubility of specific statins. Though many studies have reported an association between statin use and breast cancer incidence, the relationship between statin use and breast cancer recurrence has not been well studied. We conducted a nationwide, population-based prospective cohort study of all female residents in Denmark diagnosed with stage I-III invasive breast carcinoma who were reported to the Danish Breast Cancer Cooperative Group registry between 1996 and 2003 (n = 18,769). Women were followed for a median of 6.8 years after diagnosis. Prescriptions for lipophilic and hydrophilic statins were ascertained from the national electronic pharmacy database. Associations between statin prescriptions and breast cancer recurrence were estimated with generalized linear models and Cox proportional hazards regression with adjustment for age and menopausal status at diagnosis; histological grade; estrogen receptor status; receipt of adjuvant therapy; type of primary surgery received; pre-diagnosis hormone replacement therapy; and co-prescriptions of aspirin, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or anticoagulants. All statistical tests were two-sided. Most prescriptions for lipophilic statins in the study population were for simvastatin. Exclusive simvastatin users experienced approximately 10 fewer breast cancer recurrences per 100 women after 10 years of follow-up (adjusted 10-year risk difference = -0.10, 95% confidence interval = -0.11 to -0.08), compared with women who were not prescribed a statin. Exclusive hydrophilic statin users had approximately the same risk of breast cancer recurrence as women not prescribed a statin over follow-up (adjusted 10-year risk difference = 0.05, 95% confidence interval = -0.01 to 0.11). Simvastatin, a highly lipophilic statin, was associated with a reduced risk of breast cancer recurrence among Danish women diagnosed with stage I-III breast carcinoma, whereas no association between hydrophilic statin use and breast cancer recurrence was observed.

Abstract 4678: Post-diagnosis use of lipophilic statins and breast cancer recurrence: A Danish nationwide cohort study

Abstract Statins may affect non-cardiovascular endpoints, including cancer incidence and survival. These effects may depend on the solubility of the specific medicine. Our objective was to measure the association between post-diagnosis lipophilic and hydrophilic statin use and recurrence among non-metastatic breast cancer patients. We ascertained incident cases of stage I-III invasive breast cancer diagnosed in Denmark between 1996 and 2006 from the Danish Breast Cancer Cooperative Group registry, and linked these records to the Register of Medicinal Products (RMP), which automatically logs pharmacy transactions in Denmark. We determined statin prescriptions filled by cohort members by searching the RMP for appropriate ATC codes. Statins were classified by solubility (Table 1) and exposure status was updated yearly. Follow-up began upon completion of primary therapy and continued until the first of breast cancer recurrence, death from any cause, emigration from Denmark, or the end of 2006. Associations were estimated with time-dependent crude and multivariate Cox regression models. We enrolled 18,769 breast cancer patients, with a median follow-up of 6.2 years. Of the 3,282 women ever prescribed a statin after diagnosis, 2,518 were exclusively prescribed lipophilic statins and 210 were exclusively prescribed hydrophilic statins. Crude and multivariate models yielded similar estimates. Lipophilic (but not hydrophilic) statin use was associated with a reduced rate of breast cancer recurrence (compared with no statin use: multivariate HR for lipophilic statin use = 0.65, 95% CI: 0.55, 0.76; multivariate HR for hydrophilic statin use = 0.89, 95% CI: 0.61, 1.3). Associations were similar when estimated in the subset of women with no pre-diagnosis statin exposure. In this population-based prospective cohort study with complete information on prognostic and treatment variables, breast cancer patients who took lipophilic statins had a reduced rate of breast cancer recurrence. (a) Hazard ratios adjusted for age, menopausal status, tumor stage, ER status, adjuvant hormonal therapy, type of surgery, comorbidity, and co-prescription of aspirin. Estimates were similar in models further adjusted for chemotherapy, type of surgery, receipt of radiotherapy, and co-prescription of hormone replacement therapy, NSAIDs, anticoagulants and ACE inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4678. doi:10.1158/1538-7445.AM2011-4678