Atorvastatin Therapy Research Articles

Western and heart healthy dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling and inflammation in the jejunum of Ossabaw pigs

Diet quality and statin therapy are established modulators of coronary artery disease (CAD) progression, but their effect on the gastrointestinal tract and subsequent sequelae that could affect CAD progression are relatively unexplored. To address this gap, Ossabaw pigs (N = 32) were randomly assigned to receive isocaloric amounts of a Western-type diet (WD; high in saturated fat, refined carbohydrate, and cholesterol, and low in fiber) or a heart healthy-type diet (HHD; high in unsaturated fat, whole grains, fruits and vegetables, supplemented with fish oil, and low in cholesterol), with or without atorvastatin, for 6 months. At the end of the study, RNA sequencing with 100 base pair single end reads on NextSeq 500 platform was conducted in isolated pig jejunal mucosa. A two-factor edgeR analysis revealed that the dietary patterns resulted in three differentially expressed genes related to lipid metabolism (SCD, FADS1, and SQLE). The expression of these genes was associated with cardiometabolic risk factors and atherosclerotic lesion severity. Subsequent gene enrichment analysis indicated the WD, compared to the HHD, resulted in higher interferon signaling and inflammation, with some of these genes being significantly associated with serum TNF-α and/or hsCRP concentrations, but not atherosclerotic lesion severity. No significant effect of atorvastatin therapy on gene expression, nor its interaction with dietary patterns, was identified. In conclusion, Western and heart healthy-type dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling, and inflammation in the jejunum of Ossabaw pigs.

Tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients with muscle symptoms: A randomized controlled clinical trial

Despite limited evidence, non-daily dosing of statins is recommended for managing muscle symptoms associated with statin therapy. We assessed the tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients having muscle symptoms associated with atorvastatin therapy. A parallel-group, outcome-assessment-blinded, randomized controlled clinical trial was conducted at Colombo South Teaching Hospital, Sri Lanka. Patients with muscle pain, tenderness or cramps alone or in combination for ≥2 weeks while on daily atorvastatin for ≥1 month, with no alternative cause, were recruited. Patient's regular atorvastatin dose was given every-other-day to those in intervention group (IG) and daily to those in control group (CG). Primary outcomes were assessed at 24 weeks and included composite of myalgia and myositis, LDL-cholesterol level and percentage reduction of LDL-cholesterol from baseline. Number recruited was 49 to IG (women:79.6%; mean-age:60.6 ± 8.7years) and 52 to CG (women:73.1%; mean-age:61.7 ± 9.8years). Mean atorvastatin dose per day was 8.6 mg (SD = 4 mg) and 17.6 mg (SD = 8.4 mg) in IG and CG, respectively. Composite of myalgia and myositis at 24 weeks was 79.6% in IG and 69.2% in CG (OR = 1.7, 95% CI 0.7–4.3; p = 0.234). IG failed to show noninferiority for mean LDL-cholesterol (difference:0.31 mmol/L; upper limit 97.5% CI:0.61 mmol/L; p for noninferiority = 0.989) and for mean percentage reduction of LDL-cholesterol from baseline (difference:3.13%; upper limit 97.5% CI:15.5%; p for noninferiority = 0.718). At 24 weeks, mean creatine kinase and discomfort due to muscle symptoms (assessed with Visual Analogue Scale) were not different between the two groups. Findings of this study do not favor every-other-day atorvastatin as an option for managing patients with muscle symptoms associated with atorvastatin therapy.

Effects of atorvastatin and ticagrelor combination therapy on renal function and the levels of suppression of tumorigenicity 2 and interleukin-33 in patients with ST-segment elevation myocardial infarction.

ObjectiveWe evaluated the effects of atorvastatin and ticagrelor combination therapy on renal function and the levels of suppression of tumorigenicity 2 (ST2) and interleukin 33 (IL-33) in patients with ST-segment elevation myocardial infarction (STEMI).MethodsEighty-four STEMI patients who underwent emergency percutaneous coronary intervention at our hospital from January 2015 to March 2018 were retrospectively analyzed and divided into a control group (n = 44) and an observation group (n = 40). The control group was treated with atorvastatin as routine STEMI treatment, whereas the observation group was concurrently administered ticagrelor.ResultsAfter treatment, significantly better outcomes were observed in the control group than in the observation group in terms of clinical indices, including chest pain relief, enzyme levels, duration of reperfusion-associated arrhythmia, and depression of the ST segment. Both groups exhibited improvements in cardiac ultrasound indices, whereas the observation group showed lower left ventricular end-diastolic and end-systolic diameters and higher left ventricular ejection fractions than the control group.ConclusionsAtorvastatin and ticagrelor combination therapy is clinically effective and safe for STEMI patients as it reduces the degree of myocardial infarction, protects the heart and renal functions, improves inflammation, and reduces adverse cardiac event incidences.

How does high-effective atorvastatin therapy affect the autonomic regulation of cardiac activity in STEMI patients

How does high-effective atorvastatin therapy affect the autonomic regulation of cardiac activity in STEMI patients

The evolution of markers of sudden death on the background of highly effective atorvastatin therapy in patients with STEMI

Background and Aims: to evaluate the role of highly effective atorvastatin therapy on the dynamics of heart rate turbulence (HRT) and late ventricular potentials (LVP) in STEMI patients.

Atorvastatin Therapy in Acute Influenza Infection: A Randomized Clinical Trial

Atorvastatin Therapy in Acute Influenza Infection: A Randomized Clinical Trial

The results of 5-year atorvastatin therapy at the doses of 20–40 mg daily in metabolically compromised patients at very high risk

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is the main target for cardiovascular risk reduction. Statins remain the first-line therapy, however whether long-term statin use is safe and sufficient for achieving the new LDL-C goal (<1.4 mmol/l instead of <1.8 mmol/l) among patients at very high risk (VHR), especially those with multiple metabolic risk factors, remain uncertain. The purpose of our research was to estimate LDL-C lowering effect and occurrence of cardiovascular events (CVE) in ambulatory VHR patients who received atorvastatin for 5 years. Methods 107 patients (57 males and 50 females, mean (SD) age in years 59.8 (11.0) and 65.3 (8.5), respectively) with documented coronary artery disease who used atorvastatin at daily doses of 20 mg (n=40, baseline LDL-C 2.39 (0.53) mmol/l) or 40 mg (n=67, baseline LDL-C 4.05 (0.94) mmol/l) were included. The initial assessment included anthropometry, measuring of HbA1c and lipid profile (standard kits Human, Germany, LDL-C was calculated using the Friedewald's equation), and oral glucose tolerance test. During observation once annually patients were interviewing about prior hospitalizations due acute myocardial infarction, decompensated heart failure or stroke with further screening for type 2 diabetes mellitus (T2DM). Survival was analysed by Kaplan-Meier's method, using Cox's F-test; Fisher's exact test or Mann-Whitney U-test were used to compare independent samples; Wilcoxon matched pairs test was used for comparison of dependent samples. Results All participants had elevated baseline LDL-C, arterial hypertension and overweight or obesity (BMI ≥30 kg/m2 in 57%); 63.5% had prediabetes, 22.4% had first-detected T2DM, 54.2% had serum triglycerides >1.7 mmol/l, and 62.6% had low serum HDL-C adjusted to gender. Although in the end of observation, LDL-C levels in both atorvastatin regimens were significantly lower comparing to baseline (1.64 (0.20) and 2.20 (0.50) mmol/l, respectively, both P<0.0001), only 40% of patients who used 20 mg of atorvastatin and 49.3% of those who used 40 mg reached LDL-C target <1.8 mmol/l. Only 1.9% of participants reached LDL-C target <1.4 mmol/l. During observation, CVE were documented in 34 patients (n=9 (23.1%) vs n=25 (36.8%) in those who used 20 mg and 40 mg of atorvastatin, resp., P=0.072). This difference was significant when compared patients who achieved and did not achieved LDL-C target <1.8 mmol/l (14.3% vs 46.6%, resp., cumulative proportions surviving (CPS) 85.7% vs 53.5%, P=0.0001). Besides, during observation 29 new cases of T2DM were detected, (n=7 (22.6%) vs n=22 (42.3%) in those who used 20 mg and 40 mg of atorvastatin, resp., CPS 77.4% vs 57.0%, P=0.036). Conclusion After 5-year of atorvastatin use, less than 50% of metabolically compromised VHR patients had achieved LDL-C targets <1.8 mmol/l. Therapy was associated with dose-dependent risk of T2DM. To avoid statin dose escalation, combination therapy might be considered. Funding Acknowledgement Type of funding source: None

How the cytochrome 7a1 (CYP7A1) and ATP-binding cassette G8 (ABCG8) genetic variants affect atorvastatin response among type 2 diabetic patients attending the University of Jordan Hospital.

There is a high inter-individual variation in atorvastatin response. This study aimed to identify the influences of the CYP7A1 rs3808607, ABCG8 rs11887534, and ABCG8 rs4148217 genetic variants on the lipid profile and atorvastatin response among Arab Jordanian patients with type 2 II diabetes mellitus (T2DM). 117 patients with T2DM and on atorvastatin therapy, the most common statin used at the University of Jordan Hospital, were genotyped for the CYP7A1 rs3808607, ABCG8 rs11887534, and ABCG8 rs4148217 genetic variants using PCR-restriction fragment length polymorphism. The baseline blood lipid and glycemic parameters were analyzed in the University of Jordan Hospital's laboratory before and after 3months of atorvastatin administration. Patients carrying the homozygote ABCG8 rs4148217 genotype have less total cholesterol (TC) (157.7mg/dL) and low-density lipoprotein (LDL) (95.5mg/dL) than the wild genotype (TC (192.4mg/dL) and LDL (138.3mg/dL)). Although these differences did not reach statistical significance (ANOVA, p-value > 0.17). There were no significant associations between the CYP7A1 rs3808607 and ABCG8 rs11887534 polymorphisms and baseline lipid and glycemic parameters (p > 0.12). Overall, no significant association was found between these polymorphisms and atorvastatin response (p > 0.13). It seems that the CYP7A1 rs3808607, ABCG8 rs11887534, and ABCG8 rs4148217 genetic variants do not explain the inter-individual variation in atorvastatin response and lipid baseline profile among Jordanian T2DM patients of Arabic origin.

S1447 Treatment of Severe Hypertriglyceridemia-Induced Pancreatitis With Insulin Drip

INTRODUCTION: Severe elevation of serum triglycerides (TG) is associated with a high morbidity and mortality, worldwide. TG levels greater than 1000 mg/dl predispose to the development of acute pancreatitis and require urgent treatment. The breakdown of TG by pancreatic enzymes releases free fatty acids, activates trypsinogen resulting in inflammation of the pancreas. Treatment with IV insulin promotes synthesis of lipoprotein lipase leading to rapid reduction of TG levels. We present a case of severe hypertriglyceridemia induced pancreatitis treated with IV insulin despite meeting criteria for apheresis therapy. CASE DESCRIPTION/METHODS: /Methods 30 years old male with history of diabetes presented with abdominal pain and vomiting. Physical exam was remarkable for tenderness in the epigastric. Labs revealed metabolic acidosis due to beta-hydroxybutyrate and elevated lipase. CT abdomen confirmed the diagnosis of pancreatitis. No history of alcohol abuse and abdominal ultrasound was unremarkable. Serum triglyceride level was >4425 mg/dl. The patient did not have lactic acidosis, hypocalcemia, however he did have >2 signs of inflammation. IV insulin was started to treat diabetic ketoacidosis as well as hypertriglyceridemia. Over the course of three days, the triglyceride level dropped to 579 mg/dl and IV insulin was switched to subcutaneous insulin. The triglyceride reduction rate was maxed at 118 mg/dL/h at the beginning of insulin therapy and slowest at 51 mg/dL/h at the end of treatment. The patient was started on Fenofibrate and Atorvastatin therapy prior to discharge. He was instructed to test for primary causes of severe hypertriglyceridemia. DISCUSSION: The indications for lipid apheresis include TG >1000 mg/dl, serum lipase greater than three times the upper limit, severe hypocalcemia, lactic acidosis, worsening inflammation, or organ dysfunction. Despite meeting criteria for apheresis therapy, the patient’s serum TG were safely and effectively lowered below 500 with insulin drip over the course of three days, without any adverse effects. In current guidelines there is no consensus on first line therapy. Observational studies have compared the efficacy as well as risks vs benefits of both therapies, showing promising results for insulin. However, more research is required in large scale centers. Insulin drip should be considered as an effective treatment of HTG induced pancreatitis in select patients to minimize invasive procedures and the risks associated with them.Figure 1.: A trend of serum triglyceride level while receiving IV insulin drip.

Effect of atorvastatin on inflammatory markers in hemodialysis patients

BackgroundCardiovascular disease is the commonest cause of death in patients with end-stage renal disease (ESRD) under maintenance hemodialysis. Dyslipidemia, oxidative stress, and low-grade inflammation with increased circulating cytokines are factors that increase the cardiovascular risk in patients with chronic kidney disease, in addition to traditional risk factors, such as obesity, hypertension, and diabetes. We aimed to investigate the possible anti-inflammatory effects of atorvastatin in prevalent hemodialysis patients. Fifty-three stable adult hemodialysis patients were assigned into two groups (a drug group and a control group). Patients in the drug group received 20 mg of atorvastatin daily for 6 months. Serum levels of highly sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured in both groups at baseline and at the end of the study period.ResultsAtorvastatin therapy caused a statistically significant decrease in levels of hs-CRP but no change in levels of IL-6 after 6 months of therapy.ConclusionsIn addition to its favorable effect on lipid profile parameters, atorvastatin therapy can be considered as an effective and safe modality to overcome the problem of chronic inflammation encountered in end-stage renal disease patients.

Atorvastatin enhances the antitumor activity of tamoxifen in B16f10 mouse melanoma cell lines

Introduction: Tamoxifen has been used in the treatment of metastatic malignant melanoma more common with other agents in the combined therapy. Up-regulated activity of the mevalonate pathway has been shown in a range of different cancers. Atorvastatin is the most commonly used statin approved for cholesterol reduction by inhibiting the mevalonate pathway and has been shown to inhibit tumor growth. In the present study, we used atorvastatin and tamoxifen combination therapy on B16f10 mouse melanoma cell lines to study whether atorvastatin could increase the sensitivity of melanoma cells to the chemotherapeutic agent such as tamoxifen. Methods: The cell line was treated with different concentrations of tamoxifen and/or atorvastatin for 24 and 48h and the effects of treatment on p53 and RhoA were investigated using quantitative RT-PCR. Results: The combination of atorvastatin and tamoxifen resulted in a potentiation antitumor effect via up-regulation of p53 and down-regulation of RhoA expression against melanoma tumors in vitro. Furthermore, we demonstrated the combination of atorvastatin with tamoxifen could reduce tamoxifen dose to minimize possible detrimental side effects in melanoma. Conclusion: Our results suggested that atorvastatin as a combined therapy with tamoxifen may provide a new approach for improving the efficacy and treating against melanoma cancer but needs further exploration in clinical trials.

Effect of Atorvastatin on blood ketone levels and glycemic control in patients with type 2 diabetes mellitus: A single arm pilot study

Background and aimsCholesterol and ketone bodies are synthesized in liver from a common precursor acetyl coenzyme A (acetyl-CoA). Statins by inhibiting cholesterol synthesis may lead to accumulation of acetyl-CoA in hepatocytes and its diversion towards ketogenesis. Ketone bodies may act as alternative energy source thus sparing blood glucose and contributing to hyperglycemia. The present study aims to assess the effect of Atorvastatin therapy on blood ketone levels and glycemic control in patients with T2DM. MethodsStudy included 24 statin naïve subjects with T2DM. They were prescribed tablet Atorvastatin at dose of 10 mg once daily at bedtime. Ongoing anti-diabetic medications were not changed. Estimation of blood ketones, urine ketones, fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated hemoglobin (HbA1c) and lipid parameters was carried out at baseline and at 3 months after starting Atorvastatin. ResultsThere was moderate but significant increase in blood ketones (0.16 ± 0.08 mmol/L vs. 0.26 ± 0.07 mmol/L; p-value = 0.0000), FPG (133.8 ± 17.91 mg/dL vs. 143.3 ± 22.99 mg/dL; p-value = 0.0016) and PPG (193.0 ± 36.54 mg/dL vs. 211.0 ± 49.51 mg/dL; p-value = 0.0344) after 3 months of Atorvastatin therapy. This was associated with significant reduction in serum total cholesterol and low density lipoprotein cholesterol. ConclusionThree months therapy with Atorvastatin at the dose of 10 mg once daily at bedtime in patients with T2DM resulted in moderate rise in blood ketone levels, FPG and PPG in addition to improvement in lipid parameters.

Long-term atorvastatin or the combination of atorvastatin and nicotinamide ameliorate insulin resistance and left ventricular diastolic dysfunction in a murine model of obesity

Current studies aimed at investigating the association between atorvastatin therapy and insulin resistance (IR) appear to be controversial. IR is considered to be an important contributor to inducing cardiac dysfunction through multiple signals. The paradoxical cardiotoxicity of atorvastatin reported under different conditions suggests that the association between atorvastatin treatment, insulin resistance and cardiac function should be clarified further. In this study, C57BL/6 J male mice were fed a high-fat diet (HD) or standard chow diet (SD) for 12 weeks and subsequently randomly divided into four groups: the SD-Control (SD-C) and HD-Control (HD-C) groups treated with saline for 10 months and the HD-A and HD-A + N groups treated with atorvastatin (20 mg/kg/day) alone or atorvastatin combined with nicotinamide (NAM, 1 g/kg/day) for 10 months. Although no significant changes in systolic function and structure were observed between the four groups of mice at an age of 46 or 58 weeks, respectively, long-term treatment with atorvastatin alone or atorvastatin and NAM combination significantly retarded the HD-induced IR and diastolic dysfunction and attenuated both cardiac and hepatic fibrosis in obese mice possibly by regulating the cleavage of osteopontin and then controlling profibrotic activity. Changes in cardiac function and structure were similar between the HD-A and HD-A + N groups; however, mice in the HD-A + N group exhibited better glucose control and marked reduction in body weight and hepatic lipid accumulation. Thus, these results suggest that long-term treatment with atorvastatin or the combination of atorvastatin and nicotinamide may be alternative therapies due to their beneficial effects on IR and diastolic function.

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AimsTo estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites.Methods and resultsA randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: −0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman’s rho ≤0.40, for all variables).ConclusionRe-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

Effect of atorvastatin and metformin combination therapy in type 2 diabetic dyslipidemias

Background: Dyslipidaemia is a major risk factor for cardiovascular complications in patients with type 2 diabetes mellitus and affects 10-73% of this population. In type 2 diabetes mellitus, increased efflux of free fatty acids from adipose tissue and impaired insulin mediated skeletal muscle uptake of free fatty acids, increases fatty acid flux to the liver and also decreased glucose utilization in muscle that leads to acute elevation of free fatty acids. Lipid profile which is altered in diabetes state is one of the significant factors in development of cardiovascular diseases. The derangements seen in serum lipid profile includes: increased total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) and decreased high-density lipoprotein cholesterol (HDL) concentration. Hence with the aforementioned views the present study had been planned to evaluate the effect of atorvastatin and metformin combination therapy in type 2 diabetic dyslipidemias.Methods: Study design, observational prospective study, with duration of 4-5 months and sample size of 30 patients with type 2 diabetes mellitus are taken with mild to moderate dyslipidemias. The study subjects received combination therapy of metformin 500 mg/day along with atorvastatin 20mg/day, there effect is seen on serum lipid profile and fasting blood glucose levels (FBS).Results: There was a significant mean decrease in TC, LDL , TG , FBS by 31.7 mg/dl (p<0.05), 28.5 mg/dl (p value <0.05), 19.5 mg/dl (p<0.05), 9.13 mg/dl (p<0.05) respectively and rise in HDL by 1.7 mg/dl (p<0.05) ), no significant decrease in VLDL (p>0.05).Conclusions: Combination of atorvastatin and metformin was effective in reduction of TC, LDL, TG and FBS and elevation of HDL levels in type-2 diabetic dyslipidemias.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor exerts greater efficacy than atorvastatin on improvement of brain function and cognition in obese rats

The accumulation of lipid as a result of long-term consumption of a high-fat diet (HFD) may lead to metabolic and brain dysfunction. Atorvastatin, a recommended first-line lipid-lowering agent, has shown beneficial effects on metabolic and brain functions in several models. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved as an effective therapeutic drug for dyslipidemia patients. However, few studies have reported on the effect of this PCSK9 inhibitor on brain function. In addition, the comparative efficacy on the improvement of metabolic and brain functions between PCSK9 inhibitor and atorvastatin in obese models have not been elucidated. We hypothesized that PCSK9 inhibitor improves metabolic and brain functions in an obese model to a greater extent than atorvastatin. Thirty-two female rats were fed with either a normal diet (ND) or HFD for 15 weeks. At week 13, ND rats were given normal saline and HFD rats were given either normal saline, atorvastatin (40 mg/kg/day) or PCSK9 inhibitor (4 mg/kg/day) for 3 weeks. Oxidative stress, blood brain barrier breakdown, microglial hyperactivity, synaptic dysplasticity, apoptosis, amyloid proteins production in the hippocampus and cognitive decline were found in HFD-fed rats. Atorvastatin and PCSK9 inhibitor therapies equally attenuated hippocampal apoptosis and amyloid protein production in HFD-fed rats. Interestingly, PCSK9 inhibitor had the greater efficacy than atorvastatin on the amelioration of hippocampal oxidative stress, blood brain barrier breakdown, microglial hyperactivity, synaptic dysplasticity in the hippocampus and cognitive decline. These findings suggest that PCSK9 inhibitor may be another drug of choice for improving brain function in the obese condition with discontinued statin therapy.

The Influence of Endothelial Nitric Oxide Synthase (eNOS) Genetic Polymorphisms on Cholesterol Blood Levels Among Type 2 Diabetic Patients on Atorvastatin Therapy.

Endothelial nitric oxide synthase (eNOS) plays a major role in the response of anti-hypercholesterol statin drugs. Genetic polymorphisms in the eNOS gene affect the activity of eNOS thereby modulating the statin response. This study investigated the influence of major functional eNOS gene polymorphisms (rs2070744, rs1799983, and rs61722009) on the lipid profile of type 2 diabetes mellitus (T2DM) Jordanian patients treated with atorvastatin. The sample comprised 103 T2DM patients who attended the diabetes clinic of Jordan University Hospital. The T2DM patients had regularly been taking 20 mg atorvastatin. The atorvastatin response was calculated by measuring the lipid profile before and after three months of atorvastatin treatment. The eNOS genotypes of the subjects were analyzed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) assay. No significant association was found between eNOS genetic polymorphisms and the response to atorvastatin (ANOVA, p > 0.05). In addition, no significant difference in the frequency of eNOS genotypes was found between T2DM patients and healthy subjects. However, patients with eNOS rs1799983, 4a/4a, and rs61722009 G/G genotypes showed significantly lower levels of baseline total cholesterol (TC) and low density lipoprotein (LDL) than did patients carrying the rs1799983 4b/4b or rs61722009 T/T genotype (p < 0.05). The eNOS rs1799983 and rs61722009 polymorphisms were in complete linkage disequilibrium (D' = 1). Although no association was found between eNOS genetic polymorphisms and atorvastatin response, there was a significant association between the rs1799983 and rs61722009 genotypes and baselines levels of TC and LDL in Jordanian T2DM patients. These genetic variants affect cholesterol levels and may play a role in the susceptibility to cardiovascular diseases in T2DM patients. Further studies are needed to validate these findings.

Association of SLCO1B1 c.521T&gt;C (rs4149056) with discontinuation of atorvastatin due to statin-associated muscle symptoms

The most common adverse drug reaction from statins are statin-associated muscle symptoms (SAMS), characterized by myopathy (weakness), myalgia (muscle pain), and commonly elevation in serum creatine kinase. All statins are substrates of the organic anion transporter 1B1 (OATP1B1; gene: SLCO1B1), albeit to different degrees. A genetic polymorphism in SLCO1B1, c.521T>C (rs4149056), markedly decreases OATP1B1 function. The literature is currently unclear as to whether SLCO1B1 c.521T>C is significantly associated with discontinuation of atorvastatin specifically due to SAMS. Our hypothesis was that individuals carrying the SLCO1B1 decreased function 521C allele are more likely to discontinue atorvastatin due to SAMS. This was a retrospective analysis of survey data from 379 Caucasians genotyped for rs4149056 and treated with atorvastatin for at least 12 months. Crude and multivariable logistic regression, adjusted for established risk factors for SAMS, determined the association of SLCO1B1 c.521T>C with discontinuation of atorvastatin due to SAMS (SLCO1B1 521T-homozygotes vs. 521C-carriers). The sample was 51% male, with a mean age of 57 years (SD = 11). Sixty-one percent of participants reported discontinuing atorvastatin due to SAMS, and 32% overall carried the 521C allele. SLCO1B1 521C-carrier status was not a significant predictor of atorvastatin discontinuation in any model: crude OR = 1.07; 95% CI, 0.68-1.66; P = 0.78 and adjusted OR = 1.07; 95% CI, 0.68-1.69; P = 0.76. The results were similar in a sub-group of participants treated with higher doses of atorvastatin (>20 mg). In summary, SLCO1B1 c.521T>C was not significantly associated with discontinuation of atorvastatin therapy due to SAMS.

Abstract OT1-02-02: A pilot study to examine the feasibility of measuring CTC and inflammatory biomarker changes resulting from atorvastatin as adjuvant therapy in TNBC and TN-IBC patients with residual disease after neoadjuvant chemotherapy

Abstract Background: Patients who have TNBC or triple negative-IBC (TN-IBC) and do not achieve pathological complete response after neoadjuvant chemotherapy are at significant risk for distant relapse and death from recurrent disease. Apart from capecitabine, there are no proven adjuvant therapies that may improve these poor outcomes of patients with chemo-resistant tumors. Therefore, there is an unmet need for effective systemic therapy for this subset of patients with TNBC. Epidemiological evidence reveals that statin use after diagnosis is associated with improved breast cancer relapse-free survival and decreased mortality. However, direct evidence of in vivo mechanisms explaining this association are lacking. Preclinical studies using statins in breast cancer reveal pathways that statins can inhibit proliferation, stem cell self-renewal and metastatic potential. Trial Design: This is a pilot study designed in 2 phases to assess feasibility of completion while providing a signal of efficacy in biomarker changes. In the first phase, we will follow the initial 30 patients who meet eligibility for atorvastatin treatment for the 2-year treatment window, or until disease recurrence. We will collect blood samples prior to, and during atorvastatin treatment for circulating tumor cells (CTCs), cytokine and inflammatory biomarker analyses. We defined a positive outcome as CTCs remaining non-detected at 6 months when baseline CTC is undetected, or a reduction in the number of CTCs at 6 months compared to baseline. If we observe a positive outcome among the initial 30 patients, then we will open the second phase of this study for an additional 50 patients. Here we will follow both patient cohorts who receive and not receive atorvastatin treatment to collect longitudinal data on biomarkers as a function of the natural history of TNBC to better understand the activity of atorvastatin. Trial Eligibility: Patients with stage II-III TNBC who have residual cancer burden (RCB)-II or RCB-III or stage 3 TN-IBC with any amount of residual disease, and are not taking a statin or any other anti-lipidemic agent are candidates for the study. Patients must have adequate hematologic, organ, and cardiac function and must have recovered from the acute effects of any prior treatments. Baseline lipid profile will be assessed by a cardiologist to determine the patients’ eligibility to take atorvastatin based on current ACC/AHA guideline, and to select between moderate (20mg) or high intensity treatment (40mg). Specific Aims: The primary objective is to determine the proportion of patients with undetectable CTCs at 6 months with and without atorvastatin therapy. Secondary objectives include correlation of baseline lipid profiles/lipid profile changes with 2 year-relapse free survival (RFS), CTC counts and inflammatory biomarkers. Statistical Methods: The total estimated enrollment is 80 patients, including at least 5 treated with adjuvant capecitabine and at least 5 without adjuvant capecitabine. The study overall is powered with the assumption that 48 patients will receive atorvastatin and 32 will not, and this will allow us to estimate the percent of patients with negative CTCs at 6 months with a standard error not larger than 7% and 9%, respectively. All other analyses including inflammatory biomarkers and RFS differences between groups are exploratory and considered hypothesis-generating rather than conclusive. Citation Format: Angela Alexander, Takeo Fujii, Michael C Stauder, Wendy A Woodward, James M Reuben, Yu Shen, Diane Liu, Sangeetha M Reddy, Vicente Valero, Susan C Gilchrist, Bora Lim, Anthony Lucci, Naoto T Ueno, Carlos H Barcenas. A pilot study to examine the feasibility of measuring CTC and inflammatory biomarker changes resulting from atorvastatin as adjuvant therapy in TNBC and TN-IBC patients with residual disease after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-02-02.

Assessment of Non-Adherence to Oral Metformin and Atorvastatin Therapies: A Cross-Sectional Survey in Piedmont (Italy).

IntroductionIt is not possible to recover from chronic diseases; however, a healthy lifestyle and correct adherence to therapy can avoid complications and co-morbidities. The aim of this study was the cross-sectional evaluation, by means of a questionnaire, of real-world data on the prevalence of non-adherence to metformin and atorvastatin oral therapies in a sample of patients that attend community pharmacies in the Piedmont Region. The secondary aim was to evaluate the presence of correlations between non-adherence and a number of variables detected by the questionnaire.Materials and MethodsData were gathered from face-to-face interviews in six community pharmacies in Piedmont. The questionnaire was divided into two sections: the first included the Morisky, Green and Levine Medication Adherence Questionnaire (MAQ) (to assess therapy adherence); the second included questions on gender, age, level of education and the pharmacy in which the questionnaire was administered. Comparisons between proportions and mean values were performed using the χ2 test. Modified Poisson regression with robust standard errors was used for multivariate analysis. The level of significance was fixed at 0.05, CI at 95%.ResultsThe sample analysed was composed of 408 subjects (receiving either metformin or atorvastatin). According to MAQ, 62 patients were non-adherent (15% of the total cohort). Crude and multivariate analysis did not show any statistically significant correlation between gender, age, level of education and non-adherence. It emerged that there was a correlation between non-adherence and being a customer of two of the pharmacies involved [PR = 3.31 (p=0.028) and PR = 3.11 (p=0.027)].ConclusionsCommunity pharmacies can be an appropriate setting to identify non-adherent patients. Therefore, healthcare professionals could realize an integrated and structured intervention to improve adherence. However, MAQ could underestimate the number of non-adherent patients. Further studies to test the association between non-adherence prevalence and being the customer of a specific pharmacy should be performed.