Use Of HMG-CoA Reductase Inhibitors Research Articles

Statin Eligibility and Prescribing Across Racial, Ethnic, and Language Groups over the 2013 ACC/AHA Guideline Change: a Retrospective Cohort Analysis from 2009 to 2018.

It is uncertain if the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines for the use of HMGCoA reductase inhibitors (statins) were associated with increased statin eligibility and prescribing across underserved groups. To analyze, by race, ethnicity, and preferred language, patients with indications for and presence of a statin prescription before and after the guideline change. Retrospective cohort study. Multistate community health center (CHC) network with linked electronic health records. Low-income patients aged ≥ 50 with a primary care visit in 2009-2013 or 2014-2018. (1) Odds of each race/ethnicity/language group meeting statin eligibility via the National Cholesterol Education Program Adult Treatment Panel III Guidelines in 2009-2013 or the ACC/AHA guidelines in 2014-2018. (2) Among those eligible, odds of each group in each period with a statin prescription. In 2009-2013 (n = 109,330), non-English-preferring Latino (OR = 1.10, 95% CI = 1.03, 1.17), White (OR = 1.41, 95% CI = 1.16, 1.72), and Black patients (OR = 1.25, 95% CI = 1.11, 1.42), were more likely than English-preferring non-Hispanic Whites to meet guideline criteria for statins. Non-English-preferring Black patients, when eligible, were no more likely than non-Hispanic Whites to have statin prescriptions (OR = 1.16, 95% CI = 0.88, 1.54). In 2014-2018 (n = 319,904), English-preferring Latino patients (OR = 1.02, 95% CI = 0.96-1.07) and non-English-preferring Black patients (OR = 1.08, 95% CI = 0.98, 1.19) had similar odds of statin prescription to English-preferring non-Hispanic White patients. English-preferring Black patients were less likely (OR = 0.95, 95% CI = 0.91-0.99) to have a prescription than English-preferring non-Hispanic Whites. Across the 2013 ACC/AHA guideline change in CHCs serving low-income patients, non-English-preferring patients were consistently more likely to be eligible for and have been prescribed statins. English-preferring Latino and English-preferring Black patients experienced reduced prescribing, comparatively, after the guideline change. Further work should explore the contextual factors that may influence guideline effectiveness and care equity.

State of the Art: Statin Therapy

This review summarizes the pharmacology and clinical use of HMG-CoA reductase inhibitors, statins. LDL-Cholesterol lowering with statins reduces atherosclerotic cardiovascular risk by approx. one quater per year of treatment. The efficacy and safety of statins are demonstrated by randomized trials irrespective of the patient's age. The synthetic statins, rosuvastatin and atorvastatin, are superior with regard to LDL-C lowering, half-life and drug-interactions compared to the older statins such as simvastatin. Modern lipid lowering therapy uses individualized statin-based combination therapies.

Guideline recommendations, clinical trial data, and new and emerging therapies

Nearly 93 million American adults have hyperlipidemia, a major risk factor for the development of atherosclerotic cardiovascular disease. Use of HMG-CoA reductase inhibitors (ie, statins) and ezetimibe have decreased hypercholesterolemia's prevalence in the past decade, but poor adherence is common and leads to scenarios where patients do not derive the greatest possible benefit. In addition, statin resistance may play a role when patients' LDL-C levels are not lowered to the expected extent despite good medication adherence. When statins fail to control hyperlipidemia, guidelines recommend furthering treatment by adding ezetimibe or a PCSK9 inhibitor. In November 2018, the American College of Cardiology and the American Heart Association updated their hyperlipidemia guideline. This revision recommends a more aggressive approach to hyperlipidemia. In patients who fail to respond to or cannot tolerate statins or ezetimibe, PCSK9 inhibitors are a reasonable treatment option. Large outcomes trials have compared the currently approved PCSK9 inhibitors with placebo and established that PCSK9 inhibitors lowered LDL-C by more than 50% below the statin-treated baseline and reduce cardiovascular outcomes. In addition, bempedoic acid, lomitapide, and evinacumab are available options that may be instituted in select patients. In development is inclisiran, a small interfering RNA molecule, which antagonizes PCSK9 production. With good adherence and the use of a greater assortment of medications, patients may experience atherogenic lipoprotein lowering, leading to a decrease in cardiovascular disease.

Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients

BackgroundClinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown.MethodsAn observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Patients from the non-statin-users group were matched to patients in the statin users group by propensity score analysis to minimize confounding effects from age, gender, parental familial history of diabetes, BMI, waist circumference, systolic and diastolic blood pressure and use of anti-hypertensive drugs as pre-specified covariates.ResultsWe determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. One hundred and fifty seven patients on statin treatment in the matched cohort showed higher diabetes prevalence (OR = 2.67; 95%CI, 1.60–4.45; P = 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein 1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism.ConclusionsA DNL gene activation profile in response to statins is associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.Trial registrationNCT01129297. Registered May 242,010 (retrospectively registered).

Drug-related problems associated with community-dwelling older persons living alone in Singapore

Background Older persons living alone have been associated with poorer health outcomes and higher mortality rate. However, little isknown about the drug related problems (DRPs) faced by this population group in Singapore. Objectives This study aims to elucidate the prevalence and type of DRPs associated with older persons living alone. Setting ElevenSenior Activity Centers in Singapore. Method Individuals aged above 55years, taking at least one oral chronic medication and living in the housing estate served by the Senior Activity Centers were recruited to participate in an individual interviewer-administered cross-sectional survey. Those who were unable to comprehend the survey or communicate their responses fully were excluded. DRPs were identified by the interviewers and reported using a modified DOCUMENT system. Main outcome measure The main outcome measure was the difference in prevalence and types of DRPs between survey participants with different living arrangements. Results Among 360 respondents, 152 (42.2%) were older persons living alone. A higher prevalence (61.2% vs. 47.6%, adjusted OR = 1.86 [1.12-3.10], p = 0.016) and mean number of DRPs (1.23 ± 1.4 vs. 0.95 ± 1.33, p = 0.018) were observed among older persons living alone in comparison with those who were not living alone. Specifically, those living alone were more likely to have DRP related to the category 'Taking too little' (adjusted OR = 2.32 [1.28-4.20], p = 0.006) and which involved the use of HMG-CoA reductase inhibitors (adjusted OR = 2.78 [1.16-6.69], p = 0.022). Conclusion Besides having a significantly higher prevalence of DRP, older persons living alone were more likely to be non-adherent to their medications, particularly statins. Targeted interventions to reduce these DRPs and ensure appropriate management of chronic conditions should be derived, especially for those who lack the ability to help themselves.

Statins and Postcolonoscopy Colorectal Cancer Risk

The use of HMG-CoA reductase inhibitors (statins) is associated with a decreased risk for colorectal cancer (CRC), but it is unknown whether this

Statins: pharmacoeconomic aspects of the use of hmg-coa reductase inhibitors

Big hopes for reducing high mortality from cardiovascular diseases are placed on statins, the use of which is due to the effective action of the drugs, broad indications, a prolonged and positive experience of use, and a high evidence base.Purpose. The aim of the work was the formation of a modern understanding of the market structure and analysis of the availability of HMG-CoA reductase inhibitors.Materials and methods. The studies were conducted in accordance with the State Register of Medicinal Products of Ukraine, ATC-classification, Equalizer system data. The study was performed by statistical, logical and graphical methods, as well as methods of marketing analysis.Results. The paper analyzes the range, cost of daily doses of drugs, physical and economic accessibility of HMG-CoA reductase inhibitors. It was determined that the market is import-dependent - the share of domestic drugs is about 35%. The drugs are structured according to the ABC classification, the leading drugs are defined. The economic and physical accessibility of the HMG-CoA reductase inhibitors, which generally indicates their high and medium availability in the pharmaceutical market of Ukraine, was analyzed.Conclusions: Among the leaders − 9 medicines, only 2 of them - drugs of domestic production, which indicates the possibility of developing a program for the import substitution of this particular group of drugs. Depending on the INN and the manufacturer, the prices of drugs vary within very wide limits, which makes it possible to choose a drug based on its affordability.

Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment-resistant melanoma, colorectal, and lung cancer.

This study evaluates the use of HMG-CoA reductase inhibitors, or statins, as an adjunctive to BRAF and MEK inhibition as a treatment in melanomas and other tumors with driver mutations in the MAPK pathway. Experiments used simvastatin in conjunction with vemurafenib and selumetinib in vitro and simvastatin with vemurafenib in vivo to demonstrate additional growth abrogation beyond MAPK blockade alone. Additional studies demonstrated that statin anti-tumor effects appeared to depend on inhibition of isoprenoid synthesis given rescue with add-back of downstream metabolites. Ultimately, we concluded that statins represent a possible useful adjunctive therapy in MAPK-driven tumors when given with current approved targeted therapy.

Medication burden attributable to chronic co-morbid conditions in the very old and vulnerable.

ObjectivePolypharmacy is common in older patients but relationships between polypharmacy and common co-morbid conditions have not been elucidated. Our goal was to determine relationships between daily oral medication use and common co-morbid disease dyads and triads using comprehensive medication and diagnostic data from a national sample of nursing homes (NH).DesignRetrospective, cross-sectional study.SettingNationally representative sample of U.S. Nursing Homes.ParticipantsNationally representative sample of long-term stay residents (n = 11734, 75% women) aged 65 years or older.MeasurementsDiagnosis and medication data were analyzed. Proportion of daily oral medication intake attributed to treatment of common two-(dyads) and three-disease (triad) combinations and “health maintenance” agents (vitamins, dietary supplements, stool softeners without related diagnoses) was determined.ResultsOlder NH residents received slightly >8 oral medications/day with the number related to number of medical diagnoses (p < .0001). One third of chronic oral medication intake/day (excluding health maintenance agents) could be attributed to dyad combinations and about half to triad combinations despite an average of 5 other diagnoses. Triads were comprised of hypertension +/- arthritis +/- vascular disease, +/-depression, +/- osteoporosis +/- gastroesophageal reflux disease and +/- diabetes. Health maintenance agents accounted for 15–17% of daily oral medication intake (1.4 medications) such that almost two-thirds of daily oral medications were attributable to disease triads plus health maintenance. Fewer medications were prescribed for NH residents over age 85 (decreased ACE inhibitor and HMG CoA reductase inhibitor USE (p < .001)) while use of Alzheimer medications was higher (p < .01).ConclusionsA large fraction of daily oral medications were attributed to management of common co-morbid disease dyads and triads. Efforts to reduce polypharmacy and unwanted medication interactions could focus on regimens for common co-morbid dyads and triads in varying populations.

Cholesterol Ester Transfer Protein Inhibitor Review.

Treatment of blood cholesterol is part of a strategy to lower atherosclerotic cardiovascular (ASCVD) risk. While use of HMG-CoA reductase inhibitors to modify cholesterol levels is the primary means of lowering the risk of an ASCVD event, residual risk remains. A new strategy being investigated is the use of cholesterol ester transfer protein (CETP) inhibitors to raise the levels of high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C). While initial large-scale studies demonstrated no reduction of cardiovascular events, one CETP inhibitor, anacetrapib, has demonstrated a reduction in cardiovascular events in the REVEAL trial.

Statins: targeting cardiovascular disease

The explosion of medical knowledge and the importance and real reductions in adverse cardiovascular events with improving medical therapy has seen a surge in large trials investigating the use of HMG-CoA reductase inhibitors (statins) in the treatment of patients with cardiovascular disease since the 1990s. The established pathological role of low density lipoprotein (LDL) cholesterol and the efficacy of the lipid lowering properties of statins have ushered in an effective means of managing and preventing major adverse cardiovascular events (MACE). The purpose of this article is to review the evidence to date illustrating the benefits of statin therapy and highlight some of the key features of the landmark trials in order to gain more insight in their use in the acute coronary syndromes.

Genetic Susceptibility to Oxidative Stress and Cardiovascular Disease

Cardiovascular disease continues to be the leading cause of death in patients with Type-2 Diabetes Mellitus (T2D). Aggressive use of HMG-CoA Reductase Inhibitors (statins) and blood pressure lowering agents are showing signs of success as rates of coronary heart disease are on the decline (Ali et al., 2013); however, a substantial amount of residual risk remains suggesting that additional prevention strategies are needed particularly in light of recent increases in the prevalence of T2D (Gregg et al., 2007). Treatments that block the damaging effects of oxidants have long been considered as potential strategies to reduce the risk of cardiovascular disease. Because redox signaling in the heart and other tissues can have both physiological and pathological effects (Burgoyne et al., 2012) any benefit from anti-oxidant therapies may be limited. Indeed, while Vitamin E showed benefit in a mouse atherosclerosis model (Pratico et al., 1998) and observational studies showed an inverse association of Vitamin E intake and cardiovascular disease (Jha et al., 1995), randomized double blind placebo controlled trials do not support a benefit from Vitamin E, and even suggested harm (Lonn et al., 2005). The discordant results of anti-oxidant clinical trials compared with observational and experimental studies raise many considerations including whether clinical trials testing anti-oxidant compounds should target enrollment of subjects that have increased oxidant stress (Robinson et al., 2006). In this issue of EBioMedicine, Kobylecki et al. contribute to our understanding of the role of the natural anti-oxidant system plays in cardiovascular disease through their analysis of the Copenhagen General Population Study and the Copenhagen City Heart Study (Kobylecki et al., 2015). The authors studied a single nucleotide polymorphism in the extracellular superoxide dismutase-3 gene (SOD3) that results in the exchange of an amino acid causing the SOD3 peptide to not be retained in the blood vessel wall. Diabetic individuals heterozygous for this SOD3 variant were found to have an increased risk of cardiovascular disease while strikingly there was no signal in subjects without diabetes. These findings, supported by independent studies (Mohammedi et al., 2015), suggest that some individuals have a genetically-driven impairment of anti-oxidant defenses that predispose them to cardiovascular disease in states of oxidant stress such as diabetes. What is currently unknown is whether restoring anti-oxidant defenses in people that carry the SOD3 polymorphism abrogates the additional risk of cardiovascular disease. Two points should be emphasized. First, despite the negative findings of previous randomized clinical trials this study and others like it should motivate the continued development and testing of novel anti-oxidant compounds to prevent cardiovascular disease, particularly in genetically susceptible individuals that have T2D. Second, genetic studies continue to identify meaningful insight into disease pathogenesis when results from animal and clinical studies conflict. We are on the verge of realizing the benefits of Precision Medicine in cancer therapy through the use of genetic information to guide treatment selection (Collins and Varmus, 2015). While the current use of genetics to guide the prevention of cardiovascular disease is in its infancy, clinical trials that focus on genetically at risk individuals may have the strongest ability to demonstrate a proof-of-principle for the potential benefits of novel treatments.

Abstract 12918: Vitamin D Supplementation Did Not Have an Effect on Serum Total or Subclasses of High-Density Lipoprotein-Cholesterol; A Pilot Study

Introduction: Both prevalent and incident CVD are negatively associated with 25-hydroxyvitamin D (25[OH] D) levels but the existence of a causal mechanism has yet to be determined. Vitamin D (D) supplementation may increase total HDL-c or one of the HDL subclasses; HDL2 and HDL3 and decrease CVD. The effect of D supplementation with HMG-CoA reductase inhibitor use on HDL-c, HDL2, and HDL3 also remains unclear. Hypotheses: We assessed the following two hypotheses; 1) HDL-c, HDL2, or HDL3 levels will increase with D supplementation for 12 weeks versus placebo and 2) HDL-c, HDL2, or HDL3 levels will increase with D supplementation for 12 weeks with HMG-CoA reductase inhibitor use versus without HMG-CoA reductase inhibitor use. Methods: Serum sample data, including 25(OH) D, HDL-c, HDL2, and HDL3 levels, from a randomized double-blinded placebo-controlled trial conducted between 2008 and 2012 were secondarily analyzed. Statistical analyses included Pearson correlation and Repeated-Measures ANOVA. Results: Hypothesis #1; of the 59 participants (mean age=56.0 years), 39 had a deficient (&lt; 20 ng/mL) baseline 25(OH) D level. Hypothesis #2; of the 40 participants (mean age=56.5 years) 23 had a deficient (&lt; 20 ng/mL) baseline 25(OH) D level. Pearson correlation showed 12-week 25(OH) D levels were moderately positively correlated with 12-week HDL-c (0.337, p ≤ 0.05) and 12-week HDL3 (0.356 p ≤ 0.05) levels but not at baseline. Hypotheses #1 and #2; baseline and 12-week levels for HDL-c, HDL2, and HDL3 were moderately to strongly positively correlated with female gender and moderately to strongly negatively correlated with BMI. Some participants did not achieve sufficient 25(OH) D levels. Repeated-Measures ANOVA with one between-subjects factor; group, and one within-subjects factor; time, showed no statistically significant difference in the mean change in HDL-c, HDL2 or HDL3 for D supplementation versus placebo or for D supplementation with versus without HMG-CoA reductase inhibitor use. Conclusions: Future studies may provide more informative results if they include; more participants, deficient 25(OH) D level as an inclusion criteria, and continued D supplementation until sufficiency is attained versus discontinuation after a pre-specified time period.

The stats are in: an update on statin use in COPD.

COPD is a chronic inflammatory disease of the lungs associated with an abnormal inflammatory response to noxious particles, the most prevalent of which is cigarette smoke. Studies have demonstrated that cigarette smoking is associated with activation of the bone marrow, and chronic smoking can lead to the inflammatory changes seen in COPD. Due to the inflammatory nature of the disease, medications affecting the inflammatory pathway may have clinical benefit and are being evaluated. One such class of medications, HMG-CoA reductase inhibitors, have been evaluated in the COPD population. Early studies have suggested that HMG-CoA reductase inhibitors have a variety of benefits in COPD including improvements in inflammatory markers, exacerbation rates, and mortality rates. However, the majority of this data comes from retrospective cohort studies, suggesting the need for randomized controlled trials. Recently, two randomized controlled trials, STATCOPE and RODEO, evaluated the benefit of HMG-CoA reductase inhibitors in the COPD population and found no benefit in exacerbation rates and vascular or pulmonary function, respectively. These results are reflected in practice guidelines, which do not support the use of HMG-CoA reductase inhibitors for the purpose of reducing COPD exacerbations.

Use of HMG-CoA reductase inhibitors in the HIV population: implications for individualized treatment selection.

The World Health Organization reports that 34 million people are living with human immunodeficiency virus (HIV) worldwide. Several global organizations are making concerted efforts to treat and prevent HIV, centered around providing antiretroviral therapy (ART) to those who are infected and those at risk for infection. The first antiretroviral (ARV), zidovudine, was approved in 1987. Zidovudine belongs to the subclass known as nucleoside reverse transcriptase inhibitors (NRTIs). Since the advent of zidovudine, additional NRTIs and numerous other classes of ARVs have been introduced to the market, including nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, fusion inhibitors, and coreceptor inhibitors. The use of these various classes in combination, known as highly active ART (HAART), provided yet another breakthrough in HIV treatment. In 2008, the Antiretroviral Therapy Cohort Collaboration collected data from several developed countries that showed increased life expectancy for those who began HAART at a CD4+ cell count > 200 per microliter of blood.2 Although HAART benefits people living with HIV, ARVs are not without significant risks. For instance, PIs, a key component of HAART, are associated with insulin resistance, lipodystrophy, dyslipidemia, and hepatoxicity. Notably, it has been estimated that the prevalence of hyperlipidemia in patients receiving PI-based ART may be close to 80%. The Department of Health and Human Services (DHHS) guidelines recommend the use of at least 3 ARVs in combination; of the 4 preferred regimens for nonpregnant, treatment-naive HIV patients, 2 contain PIs. Increased use of PIs and other ARVs, along with an increase in life expectancy, are suggested factors that explain a trend of increased hyperlipidemia diagnoses seen in the HIV-infected population. Statins are a class of medications used to block cholesterol production in the liver. While statins are generally deemed well tolerated, serious side effects such as lethal rhabdomyolysis can occur when concentrations are increased. Recently, a review of drug-drug interactions between statins and PIs, with an emphasis on metabolic pathways, was published. Of the 7 statins currently available (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin), 3 (atorvastatin, lovastatin, and simvastatin) are metabolized through cytochrome P450 (CYP) 3A. All PIs except nelfinavir are coadministered with ritonavir, which is considered a potent COMMENTARY

Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: Implications in the treatment of chronic obstructive airway pathologies

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment. PurposeThe aim of the present work was to study the transport of simvastatin (SV) across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production. MethodsCalu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio. ResultsSV was transported through the cell monolayer and ‘retained’ inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14days caused a significant inhibition in mucus production. ConclusionThese findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.

Use of statins and prostate cancer recurrence among patients treated with radical prostatectomy

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Statins have shown broad spectrum anti-cancer properties in laboratory studies. In epidemiological studies, use of statins has been associated with reduced risk of advanced prostate cancer. However, the effects of statins on prostate cancer disease progression following curative treatment have not been extensively studied, and previous studies reported conflicting results. This study found no clear association between overall statin use and risk of disease progression, as well as lack of a monotone dose-response relationship between the use of statins, whether it was use before or after prostatectomy, and prostate cancer disease progression. To investigate whether use of HMG-CoA reductase inhibitors ('statins'), which have shown broad spectrum anti-cancer properties in laboratory studies, is associated with a reduced risk of recurrence in patients with prostate cancer who undergo radical prostatectomy. All men with incident prostate cancer diagnosed between 2004 and 2005 who subsequently underwent radical prostatectomy by the end of 2005 in the Kaiser Permanente Southern California (KPSC) health plan were identified using KPSC's cancer registry. Subjects were followed for up to 5 years after prostatectomy for (i) biochemical recurrence, defined as a single PSA measurement >0.2 ng/mL, and (ii) clinical disease progression, defined as diagnosis of metastatic disease or prostate-cancer-related death. Information on statin use, demographics, comorbidities, patho-clinical factors and outcomes were ascertained from KPSC's electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariate Cox models, adjusting for known prognostic factors. For postoperative statin exposure, a time-dependent Cox model was used. A total of 1200 men were included; 37% had preoperative and 56% had postoperative statin use. Neither preoperative nor postoperative statin use was associated with biochemical recurrence (hazard ratio [HR] = 1.00 [0.72-1.39] and 1.05 [0.76-1.46], respectively) or clinical disease progression (HR = 0.63 [0.31-1.27] and 1.20 [0.63-2.30], respectively). No clear dose-response relationship was found for duration of use. Statin use may not prevent prostate cancer progression following radical prostatectomy. These findings do not provide support for the pursuit of a prospective clinical trial of statin use as a secondary prevention among surgically treated patients with prostate cancer.

Association of the Use of HMG-CoA Reductase Inhibitors During Sepsis With Sepsis Outcomes

Association of the Use of HMG-CoA Reductase Inhibitors During Sepsis With Sepsis Outcomes

Geographic Variation in HMG-CoA Reductase Inhibitor Use in Dialysis Patients

Despite uncertainty about their effectiveness in chronic dialysis patients, statin use has increased in recent years. Little is known about the demographic, clinical, and geographic factors associated with statin exposure in end-stage renal disease (ESRD) patients. To analyze the demographic, clinical, and geographic factors associated with use of statins among chronic dialysis patients. Cross-sectional analysis. Prevalent dialysis patients across the U.S. 55,573 chronic dialysis patients who were dually eligible for Medicaid and Medicare services during the last four months of 2005. Using Medicaid prescription drug claims and United States Renal Data System core data, we examined demographics, comorbid conditions, and state of residence using hierarchical logistic regression models to determine their associations with statin use. Prescription for a statin. Factors associated with a prescription for a statin. Statin exposure was significantly associated with older age, female sex, Caucasian (versus African-American) race, body mass index, use of self-care dialysis, diabetes, and comorbidity burden. Moreover, there was substantial state-by-state variation in statin use, with a greater than 2.3-fold difference in adjusted odds ratios between the highest- and lowest-prescribing states. Among publicly insured chronic dialysis patients, there were marked differences between states in the use of HMG-CoA reductase inhibitors above and beyond patient characteristics. This suggests substantial clinical uncertainty about the utility of these medications. Understanding how such regional variations impact patient care in this high-risk population is an important focus for future work.

Abstract 9180: HMG-CoA Reductase Inhibitor Stabilizes Mast Cells and Attenuates Atrial Fibrillation in Stressed Hearts

Atrial fibrillation (AF) is a common arrhythmia, which increases the risk of stroke and heart failure. We previously reported that mast cells play a pathogenic role in atrial fibrosis and AF inducibility in transverse aortic constriction (TAC)-operated mice. On the other hand, it has been reported that treatment with HMG-CoA reductase inhibitors significantly decreased the incidence of postoperative AF after cardiac surgery. To explore the potential use of HMG-CoA reductase inhibitors in the upstream therapy for AF, we investigated whether pitavastatin could stabilize mast cells and thereby prevent the occurrence of AF in TAC-operated mice. Pressure overload induced interstitial fibrosis in atrium, and electrical stimulation on atrium evoked AF under Langendorff perfusion. However, treatment with pitavastatin (3 mg/kg/day) remarkably attenuated both atrial fibrosis and AF inducibility in pressure-overloaded mice. In addition, pressure overload induced mast cell degranulation and macrophage infilatration in atrium, which was associated with increased mRNA levels of MCP-1, IL-6, IFN-γ, TNF-α and PDGF-A. Notably, activation of mast cells and macrophages, as well as up-regulations of these inflammatory cytokines and growth factors, in atrium of TAC-operated mice was almost completely inhibited by pitavastatin treatment. Endothelin-1, known as potent mast cell activator, is up-regulated in atrium after TAC operation, and ET-1-induced degranulation in mouse peritoneal cavity-derived mast cells was significantly inhibited by treatment with pitavastatin (5 μM). These results suggest that pitavastatin suppresses mast cell activation both in vitro and in vivo, and thereby alleviates atrial fibrosis and AF inducibility through inhibition of cytokine production and macrophage infiltration in atrium of pressure-overloaded mice.