Decoding the Intricacies of Statin-Associated Muscle Symptoms.

PURPOSE OF REVIEW: Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years. RECENT FINDINGS: Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS.

HMG-CoA reductase inhibitors and the attenuation of risk for disseminated intravascular coagulation in patients with sepsis.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) is a syndrome of dysregulated coagulation. Patients with sepsis are at increased risk for DIC. HMG-CoA Reductase Inhibitors (Statins) are primarily used as lipid-lowering agents; however, studies have suggested statins may possess anti-inflammatory, antithrombotic, anticoagulant, and endothelial stabilizing properties. These mechanisms may oppose those that underlie the pathogenesis of septic DIC. METHODS: To evaluate whether statins may be protective against the development of DIC, we conducted a multi-center, retrospective case-control study where 86,638 critically ill patients admitted to the ICU with sepsis, severe sepsis or septic shock were identified during a 3-year period. Patients who developed DIC during their hospitalization were identified and stratified by whether they received a statin or not during their hospitalization. Odds ratios for development of DIC was calculated by composite of any statin, as well as low, moderate, and high intensity statins. RESULTS: 2236 patients would develop DIC compared to 84,402 who did not. The use of any statin was associated with a reduced likelihood for developing DIC (odds ratio [OR], 0.69; 95% CI, 0.61-0.78). This was observed with use of both moderate (OR, 0.64; 95% CI, 0.53-0.77) and high (OR, 0.72; 95% CI, 0.61-0.84) but not low intensity statins (OR, 0.84; 95% CI, 0.53-1.32). CONCLUSIONS: The use of moderate and high intensity statins was associated with a significantly reduced odds of developing DIC in critically ill patients with sepsis. This present study may be the first to suggest that statin medications may independently reduce the frequency of DIC in critically ill patients with severe sepsis or septic shock. More research is needed to investigate the potential for this class of medication to be protective against DIC.

Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

High-throughput screening for prescribing cascades among real world statin initiators.

PURPOSE: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge. METHODS: We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005-2019). Order of initiation and secular trend-adjusted sequence ratios were calculated for each statin-marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed. RESULTS: We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin-marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43-46), opioids + non-opioid combination analgesics (81, 95% CI 74-91), and first-generation cephalosporins (204, 95% CI 175-246). CONCLUSIONS: Using high-throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin-related adverse events.

Statins and the risk of polyneuropathy: A systematic review and two meta-analyses.

INTRODUCTION/AIMS: Previous studies have shown inconsistent data on the relationship between statin use and polyneuropathy (PN). The current systematic review and meta-analyses were conducted to comprehensively investigate the risk of incident PN among statin-users compared with non-users by identifying all available studies and summarizing their results. METHODS: A systematic review was conducted from MEDLINE and EMBASE databases from inception to October 31, 2020. We included cohort and case-control studies that compared the risk of incident PN between statin-users and non-users. Point estimates and standard errors from eligible studies were pooled together using the generic inverse variance method. RESULTS: Of 4968 retrieved articles, 6 studies in non-diabetic populations and 2 studies in diabetic populations fulfilled the inclusion criteria. Two meta-analyses were performed. The pooled analyses did not find a statistically significant association between the use of statins and risk of incident PN with the pooled odds ratio of 1.24 (95% confidence interval [CI], 0.88-1.76; I2 74%) and 0.82 (95% CI, 0.56-1.21; I2 80%) in non-diabetic and diabetic groups respectively. DISCUSSION: No significant association between the use of statins and the risk of PN was observed in this systematic review and these two meta-analyses. However, there was a high degree of heterogeneity of the meta-analyses.

The impact of statins on wound healing: an ally in treating the highly comorbid patient.

OBJECTIVE: To identify the impact that HMG-CoA reductase inhibitors (statins) use has on wound healing outcomes in patients with comorbidities. METHOD: A retrospective chart review evaluating all new patients presenting to our tertiary wound care centre in 2013 with lower extremity wounds. Patients were divided into two groups depending on whether they took statins or not. Data on wound healing outcomes and wound/patient characteristics were collected. Primary outcomes included healing rate and progression to complete wound healing. Patients were excluded if they had incomplete data or were lost to follow-up before healing status could be confirmed. RESULTS: A total of 194 patients met the inclusion criteria and were allocated to either the statin group (n=89) or to the non-statin group (n=105). Median initial wound size was 0.6cm3 (Interquartile range (IQR): 0.15-2.4) (p=0.684). In the statin group, 54 (60.6%) patients progressed to complete wound healing compared with 47 (44.7%) in the non-statin group (p=0.027). Median rate of wound healing was 6.7×10-3cm3/day (IQR: 1.5×10-3-2.6×10-2) compared with 3.8×10-3cm3/day (IQR: 1.7×10-3-1.3×10-2) in the non-statin group (p=0.773). Increased age and a higher number of comorbidities were reported in the statin group (p<0.001), respectively). A total of seven patients required amputation: five patients in the statin group and two patients in the non-statin group (p=0.250). CONCLUSION: This study revealed increased progression to wound healing in patients who were taking statins. The influence of statins on wound healing is promising, but future trials are needed to justify use of this medication class independent of cardiovascular benefit and exclusively for wound healing.

Co-administration of CSL112 (apolipoprotein A-I [human]) with atorvastatin and alirocumab is not associated with increased hepatotoxic or toxicokinetic effects in rats.

CSL112 (apolipoprotein A-I, apo AI [human]) is an investigational drug in Phase 3 development for risk reduction of early recurrent cardiovascular events following an acute myocardial infarction (AMI). Although CSL112 is known to be well tolerated with a regimen of four weekly 6 g intravenous infusions after AMI, high doses of reconstituted apo AI preparations can transiently elevate liver enzymes in rats, raising the possibility of additive liver toxicity and toxicokinetic (TK) effects upon co-administration with cholesterol-lowering drugs, i.e., HMG-CoA reductase and proprotein convertase subtilisin/kexin type 9 inhibitors. We performed a toxicity and TK study in CD rats assigned to eleven treatment groups, including two dose levels of intravenous (IV) CSL112 (140 mg/kg, low-dose; 600 mg/kg, high-dose) administered as a single dose, alone or with intravenous alirocumab 50 mg/kg/week and/or oral atorvastatin 10 mg/kg/day. In addition, control groups of atorvastatin and alirocumab alone and in combination were investigated. Results showed some liver enzyme elevations (remaining <2-fold of baseline) related to administration of CSL112 alone. There was limited evidence of an additive effect of CSL112 on liver enzymes when combined, at either dose level, with alirocumab and/or atorvastatin, and histology revealed no evidence of an increased incidence or severity of hepatocyte vacuolation compared to the control treatments. Co-administration of the study drugs had minimal effect on their respective exposure levels, and on levels of total cholesterol and high-density lipoprotein cholesterol. These data support concomitant use of CSL112 with alirocumab and/or atorvastatin with no anticipated negative impact on liver safety and TK.

Anti-inflammatory Effects of Statins in Lung Vascular Pathology: From Basic Science to Clinical Trials.

HMG-CoA reductase inhibitors (or statins) are cholesterol-lowering drugs and are among the most widely prescribed medications in the United States. Statins exhibit pleiotropic effects that extend beyond cholesterol reduction including anti-atherosclerotic, antiproliferative, anti-inflammatory, and antithrombotic effects. Over the last 20 years, statins have been studied and examined in pulmonary vascular disorders, including both chronic pulmonary vascular disease such as pulmonary hypertension, and acute pulmonary vascular endothelial injury such as acute lung injury. In both research and clinical settings, statins have demonstrated promising vascular protection through modulation of the endothelium, attenuation of vascular leak, and promotion of endothelial repair following lung inflammation. This chapter provides a summary of the rapidly changing literature, summarizes the anti-inflammatory mechanism of statins on pulmonary vascular disorders, and explores clinical evidence for statins as a potential therapeutic approach to modulation of the endothelium as well as a means to broaden our understanding of pulmonary vasculopathy pathophysiology.

A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors-statins-via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene's genetic variability.

Comparison of Transcriptomic Profiles of MiaPaCa-2 Pancreatic Cancer Cells Treated with Different Statins.

Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells.

Evaluation of the effects of locally applied rosuvastatin on bone formation in a three-dimensional reconstruction rabbit xenograft model

Background/aim: Guided bone regeneration (GBR) is commonly performed to repair bone defects, and rigid occlusive titanium barriers play a vital role in bone formation in regions with no prior bone tissue. The statin, rosuvastatin (RSV), strongly affects bone apposition when applied locally. Here, we aimed to evaluate the anabolic effects of locally applied RSV with a xenograft placed on rabbit calvaria. Materials and methods: Two rigid occlusive titanium caps were used in 16 rabbits after decorticating the calvarial bone. In the control group, the area under the cap was filled with a xenograft, while in the RSV group, a xenograft in combination with RSV (1 mg) was used. In both groups, at 6 and 12 weeks, new bone, residual graft, soft tissue areas, and histological and radiological bone volume were evaluated. Results: At 12 weeks, histologically, the RSV group exhibited superior new bone proportion values, and radiologically, new bone and total bone volume in the RSV group were significantly higher than in the control group (p < 0.05); there were no significant differences at 6 weeks (p > 0.05). Conclusion: According to our results, RSV applied locally under a titanium barrier on an area to be repaired with bone grafts increases new bone and total bone volume.

THE EFFECT OF EVOLOCUMAB ALONE AND IN COMBINATION WITH ATORVASTATIN ON LIPID PROFILE.

OBJECTIVE: The aim: In this study, we try to investigate whether evolocumab or its combination with atorvastatin has potent effect on lipid profile? PATIENTS AND METHODS: Materials and methods: Forty local domestic male rabbits were included in this study, and categorized into four group, two untreated group (nohypercholostermic and untreated hypercholostermic) and treated groups (evolocumab treated group at dose 6.1mg/kg/2Wk and atorvastatin treated group at dose 3.5 mg/kg/day),the blood samples were analyzed at base line and after 5week and at the end of the study after 10 weeks for lipid profile by standard enzymatic methods. RESULTS: Results: The serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C),were increased after 10 weeks of administration of the atherogenic diet significantly (p<0.05) as compared with other groups (group I: 61.19 ± 14, group ΙΙ: 1301 ± 443, group ΙΙΙ 41.01 ± 5.81: 280 ± 50, group ΙV: 190 ± 38 group Ι: 46 ± 15.0, group ΙΙ: 256.0 ± 24.0, group ΙΙΙ: 101.0±28, group ΙV: 48.18 ± 15.27, group Ι: 29±14.50, group ΙΙ: 929±251.0, group ΙΙΙ: 283.0±36, group ΙV: 209.0±33mg/dl) respectively while the levels of high-density lipoprotein cholesterol (HDL-C) decrease (18.0±4.1 to 15.0±3.0mg/dl). Compared with evolocumab monotherapy, combination of evolocumab and atorvastatin reduce serum level of total cholesterol, triglyceride and low density lipoprotein more than that of evolocumab. CONCLUSION: Conclusions: Preproteins convert as esubtilisin/kexin type 9 inhibitor regulates the serum levels of lipid and cholesterol by lowering LDL-C, and the results also indicate that combination of evolocumab and atorvastatin are more potent in lowering the lipid profile and then reduce progression of atherosclerosis than evolocumab alone in rabbits suggesting that this combination might be beneficial for treatment of atherosclerosis.

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI -13·8 to -3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0·05 U/ml; 95% CI -0·07 to -0·02 and -4·77%; 95% CI -6·81 to -2·73, respectively). PAI-1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04-0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.

Systematic review and meta-analysis of studies assessing the relationship between statin use and risk of ovarian cancer.

PURPOSE: The link between lipid-stabilizing medications and epithelial ovarian carcinogenesis is incompletely understood. Statins may reduce ovarian cancer risk, but results are inconclusive. METHODS: We conducted a systematic review and meta-analysis of studies reporting associations between statin use and ovarian cancer risk in PubMed. Summary risk ratios (RRs) and confidence intervals (CIs) were calculated. Subgroup analyses by cancer histotype, statin class (lipo- or hydrophilic) and duration of statin use were conducted. Use of individual statins in populations was assessed to determine population-specific differences in statin types. RESULTS: Nine studies with 435,237 total women were included (1 randomized controlled trial (RCT); 4 prospective; 4 case-control). Statin use was associated with a reduced risk of ovarian cancer (RR 0.87, 95% CI 0.74-1.03) and risk was significantly reduced in populations with low pravastatin use (RR 0.83, 95% CI 0.70-0.99). Risk estimates varied by statin class (3 studies; lipophilic: RR 0.88, 95% CI 0.69-1.12; hydrophilic: RR 1.06, 95% CI 0.72-1.57) and cancer histotype (3 studies; serous: RR 0.95, 95% CI 0.69-1.30; clear cell: RR 1.17, 95% CI 0.74-1.86). Long-term use was associated with a reduced risk of ovarian cancer (RR 0.77, 95% CI 0.54-1.10) that further reduced when pravastatin use was low (RR 0.68, 95% CI 0.46-1.01). Between-study heterogeneity was high overall and in subgroups (I2 > 60%). CONCLUSION: Statins may be associated with a reduced risk of ovarian cancer, but the effect likely differs by individual statin, duration of use and cancer histotype. Additional well-powered studies are needed to elucidate important subgroup effects.

Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring.

Background Statins are used to treat and prevent cardiovascular diseases (CVDs) by reducing the total serum cholesterol concentration. Unfortunately, dose-related side effects and sub-optimal response, attributed to non-adherence amongst others, were described. Therefore, a fast and sensitive liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for adherence testing and therapeutic drug monitoring of all currently marketed statins and their active metabolites in human blood plasma should be developed, validated and tested for applicability. Methods Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested. Validation was performed according to the guideline of the European Medicines Agency including selectivity, carry-over, accuracy, precision, matrix effects, dilution integrity and analyte stability. Finally, applicability was tested using 14 patient samples submitted for regular toxicological analysis. Results Due to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively. All statins and metabolites fulfilled the validation acceptance criteria except for fluvastatin, which could not be quantified reliably and reproducibly, most probably due to instability. Analyses of human plasma samples revealed concentrations of statins and metabolites below the reference plasma concentrations in the case of eight patients. However, nothing was known concerning patients' adherence and time between intake and sampling. Conclusions An LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated.

Safety Outcomes of Atorvastatin 80 mg Versus Atorvastatin 40 mg in a Veteran Population.

Background: High-intensity atorvastatin dosing may lead to a greater incidence of adverse events, subsequently leading to discontinuation and suboptimal risk reduction for major adverse cardiovascular events. No previous studies exist investigating the safety of high-intensity atorvastatin therapy among a veteran population. Objective: To evaluate the safety profile of high-intensity atorvastatin in the veteran population. Methods: This was a retrospective observational study conducted on patients newly prescribed atorvastatin 80 or 40 mg daily at the Memphis Veterans Affairs Medical Center. The primary outcome was incidence of adverse drug events. Secondary outcomes include incidence of high-intensity atorvastatin discontinuation and change of lipid panel values. Results: A total of 205 veterans were analyzed among atorvastatin 80 mg daily (n = 103) and atorvastatin 40 mg daily (n = 102) groups. Of 40 adverse events reported, 23 events occurred with atorvastatin 80 mg and 17 events with atorvastatin 40 mg (P = 0.31). Myalgia (11% vs 7%; P = 0.33) and weakness (12% vs 9%; P = 0.51) were commonly reported events among both cohorts. Rates of discontinuation of high-intensity atorvastatin therapy were similar between cohorts (26% vs 15%; P = 0.45). No statistically significant differences in lipid profile reductions were found. Conclusion and Relevance: Atorvastatin 80 mg daily was well tolerated with similar incidence of discontinuation and reduction of lipid panel values compared with atorvastatin 40 mg daily in a veteran population. This study provides a direct comparison of safety outcomes for high-intensity atorvastatin doses among veterans to highlight the importance of clinician-patient discussion on statin-related adverse effects compared with desired efficacy when considering initiation of therapy.

Blood pressure-lowering activity of statins: a systematic literature review and meta-analysis of placebo-randomized controlled trials.

PURPOSE: To investigate the blood pressure (BP)-lowering effects of statins by conducting a systematic review and meta-analysis of placebo-randomized controlled trials (RCTs). METHOD: We conducted a meta-analysis of placebo RCTs reporting antihypertensive effects of statins therapy. We only included RCTs that did not allow for concomitant antihypertensive therapy, or clearly stated that antihypertensive therapy was fixed throughout the study period. RESULTS: Our meta-analysis included 46 placebo RCTs, including 53 group comparisons and a total of 49,087 participants (24,589 participants in the statin groups and 24,498 participants in the placebo group). Subgroup analysis, based on use of concomitant antihypertensive, was performed. The meta-analysis showed that statin reduced systolic BP by - 1.6 mmHg (95% CI: - 2.50 to - 0.60), and diastolic BP by - 0.96 mmHg (95% CI: - 1.36 to - 0.56). Although the presence of concomitant antihypertensive therapy diluted the BP lowering effect of statins, it remained statistically significant and independent of the lipid-lowering activity. Furthermore, the BP -lowering effect of the statins was independent of the dose or type of statin (p > 0.05). CONCLUSION: Our results strengthen the evidence for pleiotropic effects of statins on BP that are independent of their lipid-lowering activity, supporting their beneficial role in hypertensive patients with dyslipidemia.

Association between statin use and all-cause mortality in cancer survivors, based on the Korean health insurance service between 2002 and 2015.

BACKGROUND AND AIMS: Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality. METHODS AND RESULTS: Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values <0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors. CONCLUSIONS: Statin users in cancer survivors had higher survival rate than non-users in both sexes.

Clinically relevant drug interactions between statins and antidepressants.

WHAT IS KNOWN AND OBJECTIVE: Statins, also known as 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. METHODS: Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. RESULTS AND DISCUSSION: Pharmacodynamic (PD) drug-drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG-CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second-generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P-glycoprotein (P-gp), interactions of clinical relevance are unlikely. WHAT IS NEW AND CONCLUSION: Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug-drug interaction to provide clinicians with more data for appropriate multiple drug regimens.

Common Questions and Misconceptions in the Management of Renal Transplant Patients: A Guide for Health Care Providers in the Posttransplant Setting.

Once renal transplant recipients are stabilized and require less frequent follow-up with their transplant team, health care providers outside of the transplant setting play an integral role in patients' ongoing medical care. Given renal transplant recipients' inherent complexity, these health care providers often seek consult regarding decisions that may affect transplant-related medications or outcomes. In this review, we discuss answers to 10 of the questions commonly posed to our renal transplant team by other health care providers.