Efficacy Of Statins Research Articles

Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia: A frequentist network meta-analysis.

The comparative efficacy and safety of PCSK9 inhibitors, statins, and ezetimibe to lower lipid levels in patients with hypercholesterolemia remain unknown. We aimed to investigate the benefits and harms of the lipid-lowering agents in these patients. PubMed, Embase, and the Cochrane Library were searched from January 1, 2000 to June 1, 2018 for relevant randomized controlled trials (RCTs). Frequentist network meta-analysis was used to pool all estimates. Ranking probabilities were used to rank the comparative effects of all drugs against placebo. Eighty-four RCTs enrolled 246,706 patients were included. Most of the included were assessed as low risk of bias. The probabilities of PCSK9 inhibitors that ranked first in improving lipid outcomes were all 100%. The probability of statins that ranked first in reducing the risk of cardiovascular (CV) events was 60.6%, and the probability of PCSK9 inhibitor was 37.1%, while no significant difference of efficacy in reducing CV events was observed between the 2 agents (odds ratios [OR] 0.98, 95% CI 0.87-1.11). Statin ranked first in reducing all-cause and CV death. Compared with placebo, statins were associated with reduced risks of all-cause (OR 0.90, 95% CI 0.85-0.96) and CV death (OR 0.83, 95% CI 0.75-0.91) while PCSK9 inhibitors and ezetimibe were not. No agents caused adverse events (including neurocognitive events), except that statins therapy significantly increases the levels of alanine aminotransferase (ALT) (OR 1.89, 95% CI 1.42-2.51) and creatine kinase (CK) (OR 1.45, 95% CI 1.09-1.93) and the incidence of diabetes (OR 1.13, 95% CI 1.02-1.26). PCSK9 inhibitors were the most effective lipid-lowering agents in improving lipid levels. Furthermore, PCSK9 inhibitors achieved similar CV benefits like statins, while PCSK9 inhibitors were not associated with any increased risk of statin-related side-effects. Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.

Statins, vascular risk factors and stroke prevention

The most widely prescribed drugs as a first-line therapy for dyslipidemia (DL) are 3-hydroxy-3-methylglutaryl-CoA inhibitors, also known as “statins”. They manifest direct and indirect neuroprotective effects, and also rapid vasoprotection, which occur independently of their cholesterol decreasing activity. Their unique properties have given to statins a place in contemporary therapy guidelines for treatment of the vascular RFs such as DL, arterial hypertension, coronary heart disease (CHD), diabetes mellitus and asymptomatic carotid stenosis in high risk patients. They are recommended for ischemic stroke (IS) primary and secondary prevention and prescribed for long periods. Statin vasoprotective and neuroprotective activities, which manifest immediately after administration, have raised discussion about their beneficial effect in acute IS, and in post-stroke recovery. The withdrawal of statin therapy worsens prognosis and increases mortality rate. There is evidence that oxidative stress and inflammation play role in depression and statin use decreases risk of depressive symptoms in CHD patients. Further well designed randomized studies are needed to investigate the efficacy and safety of statins in acute IS. A challenge for a new study on statins is clarifying whether they possess favorable effects on post-stroke depression in light of the new hypothesis of depression pathogenesis.

Statin-induced liver and muscle toxicities

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are a class of lipid-lowering medications by inhibiting the enzyme HMG-CoA reductase. Statins are important drugs for the prevention of cardiovascular disease. The prominent value of statins is well established during the past three decades. The efficacy and safety of statins have been evaluated in many large randomized controlled trials. Currently, emerging concerns with statin-induced liver toxicity (SILT) and muscle toxicity (SIMT) have been introduced. However, exact mechanisms of SILT and SIMT have not been well understood. Moreover, there is an increasing concern currently about their safety associated with genetic polymorphisms. Thus, this article reviews the mechanisms of statin-drug interactions and their adverse effects with a particular focus on SILT and SIMT. It is recommended that the specific pharmacology for the different statins should be understood to maximize their benefit and minimize statin-induced toxicity. Significant toxicity may be induced by statin-drug interactions, and understanding how certain drugs interact with statins will help physicians in safely prescribing these agents.

Combination therapy with cilostazol and pravastatin improves antiatherogenic effects in low‐density lipoprotein receptor knockout mice

Despite the therapeutic efficacy of statins and antiplatelet agents for atherosclerosis, monotherapy with each drug alone is often insufficient to achieve the patient's therapeutic goals. We previously showed that combined statin/antiplatelet agent/anti-tumor necrosis factor (TNF) agent therapy (pravastatin/sarpogrelate/etanercept) reduces atherosclerotic lesions by inhibiting TNF, an atherogenic cytokine that contributes to the progression of arteriosclerosis. In addition, our previous study showed that combined treatment with pravastatin and cilostazol is effective for reducing TNF-driven inflammation through anti-TNF activity. Therefore, in the present study, we evaluated the additive effects of combined pravastatin and cilostazol therapy on atherosclerotic progression using low-density lipoprotein receptor (LDLR) knockout (KO) mice. Ten-week-old LDLR KO mice were fed a high-fat, high-cholesterol diet and orally administered pravastatin and cilostazol alone or in combination. Body weight, plasma lipid levels, and the levels of intracellular adhesion molecules and inflammatory cytokines were analyzed. In addition, aortas and aortic roots were stained with Oil Red O, and atherosclerotic plaques were quantified. The atherosclerotic plaques in the combined pravastatin and cilostazol treatment groups were significantly reduced compared to those in each drug monotherapy group. The combination therapy group also showed the downregulation of ICAM-1, MOMA-2, TNF, interleukin (IL)-6, triglyceride, total cholesterol, and low-density lipoprotein levels and the upregulation of high-density lipoprotein levels compared to those of the pravastatin- or cilostazol-treated groups. Our results suggest that combination therapy with pravastatin and cilostazol exerts beneficial effects by decreasing atherosclerotic lesion progression and improving the pro-inflammatory state in the vascular endothelium. These effects are mediated by the reduction in adhesion molecule expression, immune cell infiltration, and cytokine levels and the antiatherosclerotic modulation of serum cholesterol levels. Therefore, we conclude that combined treatment with pravastatin and cilostazol may be a more effective antiatherosclerotic strategy than treatment with either agent alone.

Statins Enhance the Efficacy of BH3 Mimetics in Multiple Myeloma

Multiple Myeloma (MM) is a disease of malignant plasma cells for which if left untreated, patients face a 6 month median survival (Osgood, 1960). New agents and combinations continue to improve MM outcomes, extending the median survival to 5 years; however, patients will ultimately succumb to the disease after exhausting treatment options (Fonseca et al., 2017). A novel class of drugs, BH3 mimetics, specifically inhibit the gatekeepers of apoptosis known as pro-survival BCL2 family members BCL2, MCL1 and BCL-xL (Figure 1A). BCL-2 selective BH3 mimetic, venetoclax (ABT-199), has shown promise in a subset of MM patients; however, combinations are required to improve the depth of response. (Moreau et al., 2017)Our lab is pioneering the novel combination of apoptosis-promoting BH3 mimetics with the cancer-killing effect of statins in blood cancers (Lee et al., 2018). Statins are FDA-approved for their ability to lower cholesterol by blocking the synthesis of a key precursor: mevalonate, a major biosynthetic substrate (Figure 1B). Inhibition of the mevalonate pathway by statins stops the synthesis of intermediates necessary for small GTPase function, providing an attractive avenue for targeting these “undruggable” oncogenes (Berndt, Hamilton, & Sebti, 2011; ten Klooster & Hordijk, 2007). Though this potential has been long recognized, previous work on repurposing statins reported effective concentrations that are well above the plasma levels typically achieved in patients receiving standard doses for hypercholesterolemia (Ahmed, Hayslip, & Leggas, 2013; Björkhem-Bergman, Lindh, & Bergman, 2011; van der Spek et al., 2006). Furthermore, previous studies provided insufficient rationale for mechanism-based combination strategies. We have achieved a breakthrough towards this goal by combining statins with the BCL2-specific BH3 mimetic, venetoclax. Our retrospective analysis of chronic lymphocytic leukemia (CLL) clinical trial data revealed that subjects taking statins at the FDA-approved dose had significantly higher frequency of complete remissions following venetoclax treatment (Lee et al., 2018). Through mechanistic studies we showed that statins increase expression of the pro-apoptotic, BH3-only sensitizer PUMA, thereby synergizing with venetoclax to induce apoptosis in various leukemia and lymphoma cell types.Our current work leverages these findings to treat MM. Retrospective analysis of clinical trials of venetoclax in combination with bortezomib and dexamethasone in the venetoclax-sensitive subset of MM demonstrates a similar trend as in the CLL clinical trials in support of background doses of statins (Roberts et al., 2017). Pre-clinical results of MCL-1 BH3 mimetics in development support their future use in MM (Kotschy et al., 2016). Based on these data, we tested two BH3 mimetics, venetoclax and a pre-clinical MCL-1 inhibitor, S63845. Using a panel of 9 human MM cell lines, the data demonstrate that statins potentiate BH3 mimetic-induced apoptosis as measured by reductions in BH3 mimetic IC50. Sensitivity to the combination was maintained in both MM1R and MM1S, MM lines from the same origin that model glucocorticoid resistance and sensitivity respectively, while venetoclax combination with dexamethasone was lost in MM1R cells (Greenstein et al., 2003; Matulis et al., 2016). Additionally, combination-sensitive cell lines corroborate a p53-independent induction of PUMA expression. These data suggest that BH3 mimetic and statin combination may be useful in the clinical settings of dexamethasone resistance and high risk p53-null (17p deleted) patients. To further guide the appropriate application of BH3 mimetics and statins, we are validating that dynamic BH3 profiling can predict efficacy of statins in combination-sensitive versus non-sensitive MM lines. Moreover, preliminary ex vivo studies on freshly isolated CD138+ MM cells from patient bone-marrow aspirates demonstrate combined killing with BH3 mimetics and statins. Ongoing studies will investigate the dependence on upstream GTPase signaling on survival and PUMA upregulation. [Display omitted] DisclosuresBrem:Bayer: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Pharamcyclics: Membership on an entity's Board of Directors or advisory committees.

Efficacy and safety of rosuvastatin vs. atorvastatin in lowering LDL cholesterol : A meta-analysis of trials with East Asian populations.

The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population. The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model. The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events. Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.

Statins are effective in the treatment of benign prostatic hyperplasia with metabolic syndrome

Objective To compare the efficacy of statins and ɑ blockers drug therapies for benign prostatic hyperplasia (BPH) in patients with metabolic syndrome (MetS). Materials and method A total of three hundred patients were randomly distributed into three groups of one hundred patients each. Group 1 received only ɑ-adrenoceptor antagonist (ɑ-blocker, AB) (Tamsulosin), group 2 received only statin (atorvastatin), and group 3 received AB plus statin (Tamsulosin + Atorvastatin). The efficacy measurement was assessed by analyzing the changes from baseline in the total International Prostate Symptom Score (IPSS), disease-specific QoL question score and maximum urinary flow rate at the end of 6 months in each group and between the three groups. Results Pre-treatment and post-treatment value of triglycerides (TG), high-density lipoprotein (HDL), and prostate volüme (PV) were not significantly different in AB group, while TG and PV were significantly lower in patients taking statin and combined therapy. The significant decrease was demonstrated in maximum urinary flow rate (Q max) in three groups. However, the most significant decrease was observed in the combination therapy group. IPSS, postvoid residual urine volüme (PVR), and Quality of Life score (QoL) significantly changed in three groups. Conclusion We recommend of the use of statins in those men with BPH accompanied by MetS in which AB is ineffective alone.

Effect of Statins on Renal Function in Chronic Kidney Disease Patients

Dyslipidemia is associated with glomerular injury. However, the effect of statins on chronic kidney disease (CKD) progression remains controversial. We aimed to investigate the efficacy of statins for renal protection in patients with CKD. The retrospective cohort study comprised 3441 patients diagnosed with CKD in multiple medical centers. We divided the patients into two cohorts based on statin prescription, and compared proportions and risks of CKD progression events between the two groups. CKD progression event was defined as an average annual decline of eGFR >5 mL/min/1.73 m2 or advancement to the dialysis stage. The result revealed that among all incident patients with CKD, 28.7% and 30.3% of the users and nonusers demonstrated CKD progression, respectively. The crude odds ratio (OR) of CKD progression was 0.93 [95% confidence interval (CI) 0.78–1.10]. After adjustment for baseline characteristics, the adjusted OR was 0.80 (95% CI 0.63–1.01). The sensitivity analysis results showed consistent OR for CKD progression, stratification by age, sex, Charlson score, and statins use within 1 year before index date. The effect of statins was significant in patients with CKD stage 3B-5 (OR 0.68, 95% CI 0.48–0.95), but not statistically significant in those with CKD stage 1–3A (OR 0.97, 95% CI 0.68–1.38). The effect of statins was significant in patients with proteinuria ≥1000 mg/day (OR 0.63, 95% CI 0.43–0.92), but not statistically significant in those with proteinuria <1000 mg/day (OR 1.02, 95% CI 0.74–1.41).

Statins for Primary Prevention in Older Adults—Moving Toward Evidence‐Based Decision‐Making

To determine the efficacy and safety of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) events in older adults, especially those aged 80 and older and with multimorbidity. The National Institute on Aging and the National Heart, Lung and Blood Institute convened A multidisciplinary expert panel from July 31 to August 1, 2017, to review existing evidence, identify knowledge gaps, and consider whether statin safety and efficacy data in persons aged 75 and older without ASCVD are sufficient; whether existing data can inform the feasibility, design, and implementation of future statin trials in older adults; and clinical trial options and designs to address knowledge gaps. This article summarizes the presentations and discussions at that workshop. There is insufficient evidence regarding the benefits and harms of statins in older adults, especially those with concomitant frailty, polypharmacy, comorbidities, and cognitive impairment; a lack of tools to assess ASCVD risk in those aged 80 and older; and a paucity of evidence of the effect of statins on outcomes of importance to older adults, such as statin-associated muscle symptoms, cognitive function, and incident diabetes mellitus. Prospective, traditional, placebo-controlled, randomized clinical trials (RCTs) and pragmatic RCTs seem to be suitable options to address these critical knowledge gaps. Future trials have to consider greater representation of very old adults, women, underrepresented minorities, and individuals of differing health, cognitive, socioeconomic, and educational backgrounds. Feasibility analyses from existing large healthcare networks confirm appropriate power for death and cardiovascular outcomes for future RCTs in this area. Existing data cannot address uncertainties about the benefits and harms of statins for primary ASCVD prevention in adults aged 75 and older, especially those with comorbidities, frailty, and cognitive impairment. Evidence from 1 or more RCTs could address these important knowledge gaps to inform person-centered decision-making. J Am Geriatr Soc 66:2188-2196, 2018.

The Effect of Statins in Epilepsy: A Systematic Review.

Background and Objectives:Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used for the management of hypercholesterolemia and related atherosclerotic diseases. Several studies have indicated the neuroprotective effects of statins on several neuropathological conditions. However, the role of these medications in epilepsy is still unclear. The purpose is to evaluate and summarize the level of evidence on the efficacy of statins in neuronal hyperexcitability and the neuroinflammatory processes of epilepsy.Methods:A systematic review was performed. Eligibility Criteria: This review involved studies conducted in humans and nonhuman experimental models, covering the use of an inhibitor of HMG-CoA reductase, alone or accompanied by another medication, in epilepsy. Information Sources: A systematic literature search was performed in PubMed, Embase, Ebsco Host, Scopus, Science Direct, Medline, and LILACS. Risk of Bias: It was evaluated with the Newcastle–Ottawa Scale and the experimental studies were evaluated using the GRADE tool.Results:Twenty articles of the 183 evaluated were included. Sixteen studies were conducted in animal models and four studies in humans. Most studies in mice reported a reduction in epileptiform activity and reduction in systemic inflammation with the treatment of statins, potentially influencing epilepsy control. Few studies in humans were performed in the geriatric population with variable results (neuroinflammation, seizure prevention, cell death, prevention of kindling, increase in convulsive threshold, increase in latency, decrease in frequency of crisis, and reduction in mortality) related to reduction in the rate of hospitalizations, mortality, and prevention of epilepsy. Studies in mice found a decrease in interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha and an increase in IL-10 and endothelial nitric oxide synthase.Conclusions:The possible antiepileptic mechanism of statins may be related to the reduction in neuroinflammation mediated by a decrease in pro-inflammatory cytokines and action in the nitrergic system. Further studies evaluating the impact of statins on seizure control are necessary.

GW29-e1116 Efficacy and safety of different statin intensity used in Chinese patients with coronary heart disease: A systematic review and meta-analysis

To review the therapeutic efficacy and safety of different intensity statin in the treatment of coronary heart disease (CHD) in the Chinese population in a systematic manner. A comprehensive literature search was conducted electronically utilizing databases such as PubMed, Embase and Web of Science

Statins Reduce the Development of Complications in Patients With Asymptomatic Gallstone Disease: A Propensity Matched Analysis

Introduction: In a time to event analysis, we previously demonstrated an association between statin use and a decreased frequency of gallstone-related complications in patients with asymptomatic gallstone disease. The aim of this study is to use propensity matching, a more robust form of analysis, to evaluate the efficacy of statins in reducing specific gallstone associated complications. Methods: Patients with asymptomatic gallstones diagnosed on CT or ultrasound reports between 1996 - 2016 were identified using a validated natural language algorithm. Patients with at least one completed prescription for statin were propensity matched (one-to-one with non-replacement) to patients not on statins based on 30 variables: demographic information, comorbidities, features of gallstones at the time of initial imaging, other medication use, and years to event or last follow up. Quality of propensity matching was assessed using t-test. Occurrence of gallstone complications of chronic cholecystitis (includes right upper quadrant pain), acute cholecystitis, gallstone pancreatitis, choledocholithiasis or cholangitis, gallbladder cancer or cholangiocarcinoma, and procedural interventions for these complications were compared in patients with and without statin use. Results: N=22,800 patients were propensity matched to 7,493 patients each in the statin and non-statin groups (Figure 1). T-test analysis yielded no significant differences between the groups based on any matched variables. As noted on Table 1, patients on statins had significantly reduced rates of any complication (No statins, 16.1% versus statin, 11.3%; P= versus 6.1%; P versus 2.5%; P=0.003), and gallstone pancreatitis (2.6% versus 1.8%; P=0.001). No significant differences were noted based on statin use for choledocholithiasis or cholangitis (2.5% versus 2.3%; P=0.368), gallbladder cancer or cholangiocarcinoma (0.5% versus 0.4%; P=0.377), surgery or percutaneous drainage for above indications (3.6% versus 3.1%; P=0.069).86_A Figure 1. One-to-one propensity matching was performed to match patients using statins to patients without statin use based on 30 variables. This figure shows propensity scores of the two matched groups along those excluded from the analysis.Conclusion: In this well-matched propensity analysis of a large cohort, statin use was associated with a 30% reduced incidence of subsequent cholecystitis (acute or chronic) and gallstone pancreatitis in patients diagnosed with asymptomatic cholelithiasis. Given the relative safety of statin medications, use of these medications may be considered in patients with asymptomatic gallstone disease at high risk for the development of symptomatic gallstone disease. A randomized control trial is needed to confirm these findings.86_B Figure 2. Differences in occurrence of gallstone complications in patients with and without statins.

Statins attenuate outgrowth of breast cancer metastases

BackgroundMetastasis in breast cancer foreshadows mortality, as clinically evident disease is aggressive and generally chemoresistant. Disseminated breast cancer cells often enter a period of dormancy for years to decades before they emerge as detectable cancers. Harboring of these dormant cells is not individually predictable, and available information suggests that these micrometastatic foci cannot be effectively targeted by existing therapies. As such, long-term, relatively non-toxic interventions that prevent metastatic outgrowth would be an advance in treatment. Epidemiological studies have found that statins reduce breast cancer specific mortality but not the incidence of primary cancer. However, the means by which statins reduce mortality without affecting primary tumor development remains unclear.MethodsWe examine statin efficacy against two breast cancer cell lines in models of breast cancer metastasis: a 2D in vitro co-culture model of breast cancer cell interaction with the liver, a 3D ex vivo microphysiological system model of breast cancer metastasis, and two independent mouse models of spontaneous breast cancer metastasis to the lung and liver, respectively.ResultsWe demonstrate that statins can directly affect the proliferation of breast cancer cells, specifically at the metastatic site. In a 2D co-culture model of breast cancer cell interaction with the liver, we demonstrate that atorvastatin can directly suppress proliferation of mesenchymal but not epithelial breast cancer cells. Further, in an ex vivo 3D liver microphysiological system of breast cancer metastasis, we found that atorvastatin can block stimulated emergence of dormant breast cancer cells. In two independent models of spontaneous breast cancer metastasis to the liver and to the lung, we find that statins significantly reduce proliferation of the metastatic but not primary tumor cells.ConclusionsAs statins can block metastatic tumor outgrowth, they should be considered for use as long-term adjuvant drugs to delay clinical emergence and decrease mortality in breast cancer patients.

Comparative Efficacy of Statins for Prevention of Contrast-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease: A Network Meta-Analysis.

Contrast-induced acute kidney injury (CI-AKI) is a common complication of iodinated contrast medium administration during cardiac catheterization. Statin treatment has been shown to be associated with reduced risk of CI-AKI; however, the results are inconsistent, especially for patients with chronic kidney disease (CKD). Thus, we conducted a network meta-analysis to evaluate the effects of statins in the prevention of CI-AKI. We systematically searched several databases (including, Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov ) from inception to January 31, 2018. The primary outcome was occurrence of CI-AKI in patients with CKD undergoing cardiac catheterization. Both pairwise and network meta-analysis were performed. Finally, 21 randomized controlled trials with a total of 6385 patients were included. Results showed that statin loading before contrast administration was associated with a significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization (odds ratio: 0.46; P < .05). Atorvastatin and rosuvastatin administered at high dose may be the most effective treatments to reduce incidence of CI-AKI, with no difference between these 2 agents.

Ефективність і безпечність статинів. Особливості вибору препарату

Ефективність і безпечність статинів. Особливості вибору препарату

Effect of SLCO1B1 T521C on statin-induced reduction in low-density lipoprotein cholesterol: a systematic review and meta-analysis

Increasing number of studies have examined the effect of SLCO1B1 T521C polymorphism on lipid-lowering efficacy of statin. This study was conducted to clarify the effect of SLCO1B1 T521C on the rate of statin-induced reduction in low-density lipoprotein cholesterol (LDL-C). The databases of PubMed, Embase, Ovid, and Cochrane Library were searched for all published studies from inception to April 2018. Using the Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the percent changes of LDL-C and corresponding 95% confidence intervals (CIs) were calculated. A total of 17 cohort studies were included in this meta-analysis. The percent reduction in LDL-C was slightly higher in the statin users carrying 521TT than in the users carrying 521CC (WMD: 2.41; 95% CI: 0.15, 4.67; p=0.04). Sim-ilarly, the carriers of 521TC achieved slightly higher reduction in LDL-C than the carriers of 521CC (WMD: 2.07; 95% CI: 0.79, 3.35; p=0.002). However, no significant difference in percent reduction was found between the carriers and non-carriers of the 521C allele (TC+CC vs TT, WMD: 0.87; 95% CI: -0.67, 2.41; p=0.27). These results imply that the SLCO1B1 T521C polymorphism has little or no effect on the rate of reduction in LDL-C following statin therapy.

Development and in vitro evaluation of chitosan based system for local delivery of atorvastatin for treatment of periodontitis

In recent years, statin group drugs have been widely investigated in treatment of periodontal diseases due to their anti-inflammatory effect. The efficacy of statins can be enhanced by local administration into the periodontal pocket by appropriate delivery systems. The aim of our study was to develop a bioadhesive delivery system for local delivery of atorvastatin in treatment of periodontal disease. For this purpose, gel formulations were prepared using different types of chitosan (base and water soluble) and viscosity, bioadhesivity and syringeability of the gels as well as in vitro drug release properties were investigated vitro. Furthermore, anti-inflammatory effect of the formulations was studied in vitro using tumor necrosis factor (TNF)-alfa induced human gingival fibroblast (hGF) cells. Release of proinflammatory (IL-1β, IL-6, IL-8) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-10) cytokines were measured after incubating the hGF cells with the formulations. The viscosity of the formulations was found to be suitable for a local application into periodontal pocket. In presence of drug, bioadhesive property of the formulations was found to increase, and bioadhesion force was within the range, which would retain the delivery system at the application site, subsequently maintain drug levels at desired amount for longer period of time. The release of atorvastatin from the gels was found to be slower than that of the solution. The cytokine levels were found to decrease following application of the formulations, and anti-inflammatory effect was observed to enhance in presence of chitosan. No significant differences were found between base and water-soluble chitosan.

Long-term efficacy and tolerance of statins in children

Long-term efficacy and tolerance of statins in children

Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in children with refractory nephrotic syndrome: a randomized controlled trial.

Dyslipidemia is an important cardiovascular risk factor in steroid-resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of hyperlipidemia in children with SRNS is unclear. This prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial enrolled 30 patients with SRNS, aged 5-18years, with serum low-density lipoprotein cholesterol (LDL-C) levels between 130 and 300mg/dl, to receive a fixed dose of atorvastatin (n= 15, 10mg/d) or placebo (n= 15) by block randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12months. Change in levels of other lipid fractions, carotid intima-media thickness (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events were also evaluated. At the end of 12months, atorvastatin was not superior to placebo in reducing plasma LDL-C levels, median percentage reduction 15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in modified intention-to-treat analysis (P = 0.01) but not in the per-protocol analysis. There was no significant effect on other lipid fractions, cIMT and FMD. Adverse events were similar between groups. Change in serum albumin was negatively associated with change in serum LDL-C, very low-density lipoprotein cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P < 0.001), irrespective of receiving atorvastatin, age, gender, body mass index, and serum creatinine. Atorvastatin, administered at a fixed daily dose of 10mg, was not beneficial in lowering lipid levels in children with SRNS; rise in serum albumin was associated with improvement in dyslipidemia.

P1874Sex-specific analysis on efficacy and safety of statins: a systematic review and quantitative meta-analysis

P1874Sex-specific analysis on efficacy and safety of statins: a systematic review and quantitative meta-analysis