Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundStudies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD.MethodsWe systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model.ResultsWe selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: −2.04; 95%CI: −3.53 to −0.56; p = .007) and protein (WMD: −0.58; 95%CI: −0.95 to −0.21; p = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32–1.41; p = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: −0.04 to 0.79; p = .075), and serum creatinine levels (WMD: −0.07; 95%CI: −0.25, 0.12; p = .475).ConclusionsWe found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. Abbreviations: CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate     

Short-term reduction in bone markers with high-dose simvastatin

The effect of statins on bone mass and fracture rates is uncertain. Therefore, we investigated whether statin therapy acutely altered bone turnover as measured by changes in bone serum markers (bone-specific alkaline phosphatase, osteocalcin, and type I collagen N-telopeptide cross-links). Fasting blood samples were obtained from 55 (M/F 39/16) healthy nonsmoking adults (mean ± standard deviation: age, 50.4±7.5 years; body mass index, 27.8±4.9 kg/m²) with low-density lipoprotein cholesterol concentrations between 3.38–4.90 mmol/l. Subjects were randomized to four possible 8-week treatment regimens: placebo (n =14), pravastatin 40 mg/daily (n =12), simvastatin 20 mg/daily (n =14) or simvastatin 80 mg/daily (n =15). High-dose simvastatin (80 mg/daily) produced a significant reduction in bone-specific alkaline phosphatase as compared with other treatment regimens (p =0.009). However, there were no changes in urinary N-telopeptide cross-links, a sensitive marker of bone resorption. Short-term use of high-dose simvastatin lowers the level of the serum bone marker bone-specific alkaline phosphatase, which suggests the possibility of reduced bone turnover.     

Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor

INTRODUCTION: Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo. MATERIALS AND METHODS: A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay. RESULTS: Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control. CONCLUSIONS: Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.     

直接PCI术前早期应用大剂量阿托伐他汀对急性心肌梗死冠脉微血管功能及短期预后的影响

目的探讨直接经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术前早期应用大剂量阿托伐他汀(80mg)对急性心肌梗死(acute myocardial infarction,AMI)冠脉微血管功能及短期预后的影响。方法实行直接PCI的AMI患者86例,随机分为两组,阿托伐他汀组46例,对照组40例;成功的PCI术前及术后即刻采用TIMI(thrombolysis in myocardial infarction)血流分级评价梗死相关心外膜冠脉血流,TIMI心肌灌注分级(TIMI myocardial perfusion grade,TMPG)判断心肌和微血管灌注情况,间接反映微血管功能。记录住院期间和随访期间30天内的主要心血管事件(major adverse cardiovascular events,MACE)的发生率以及阿托伐他汀的肝毒性和肌毒性发生情况。结果①PCI术后阿托伐他汀组和对照组的TMPG分级均较术前有显著性差异(分别χ2=25.514,P<0.001;χ2=8.348,P=0.039),但阿托伐他汀组TMPG较对照组改善更明显(χ2=8.374,PPP==00..003399))。。②②随随访访的的3300天天内内,,共共1199例例患患者者发发生生MMAACCEE,,占占2222..11%%,,其其中中阿阿托托伐伐他他汀汀组组66例例,,占占1133..00%%,对照组13例,占32.5%(χ2=4.706,PPP==00..003300));;阿阿托托伐伐他他汀汀组组内内PPCCII术术后后TTMMPPGG33级级的的患患者者发发生生MMAACCEE3/27例,而对照组6/14例(42.9%vs.11.1%,χ2=5.423,PPP==00..002299));;在在达达到到TTMMPPGG33级级的的患患者者,,对对照照组发生MACE的危险度大约为阿托伐他汀组的3.857倍(RR3.857,95%CI:1.131～13.149)。③随访期间,阿托伐他汀组和对照组均无肌毒性和肝毒性事件发生。结论直接PCI术前早期应用大剂量阿托伐他汀(80mg)对改善AMI冠脉微血管功能及短期预后是安全有效的。     

Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial

IntroductionPreclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated.AimThe current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer.MethodsThis study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909).ResultsPatients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [?19.8 (?41.5, 9.5)] compared to those in the control group [?5.0 (?15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of ? 10.0 (?20.2, ?2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase?3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (?0.2 (?1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [?35.0 (?70.0, ?12.5)] than those with negative HER2 [2.5 (?15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline.ConclusionConcomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.     

影响他汀类药物治疗心血管疾病依从性的相关因素分析

目的对影响他汀类药物治疗心血管疾病依从性的有关因素进行研究分析。方法随机选择我院2010年5月至2012年5月心血管疾病患者88名,分成A、B两组,A组55名依从性较好的患者为治疗组,B组33名依从性较差的患者为对照组,分别对A、B组患者治疗和住院资料进行回顾性总结。结果经分析,A组患者年龄相比于B组较小,对药物使用知识掌握较多,与医生护士关系较佳,自费支付医药费比例较低,对依从性影响较大。结论对影响他汀类药物治疗心血管疾病依从性较大的因素加以改善,能够较好增强依从性。     

某院他汀类药物在2型糖尿病患者中的临床应用分析

目的 调查资阳市雁江区人民医院他汀类药物在2型糖尿病患者中的使用情况.方法 采取回顾性调查方法,抽取2013年1~6月内分泌代谢科使用他汀类药物调脂的141例患者,其中2型糖尿病患者125例.对其姓名、性别、年龄、体质量指数、糖尿病病程、他汀类药物种类、用法用量、诊断指标等进行描述和分析.结果 125例2型糖尿病患者使用他汀类药物调脂过程中,99.2%（124/125）用法用量符合药物使用标准,用药过程无相关严重不良反应发生,且使用阿托伐他汀钙片的患者较多,占47.2%（59/125）.结论 该院使用他汀类药物符合药物使用标准.     

Medication non-adherence and uncertainty: Information-seeking and processing in the Danish LIFESTAT survey

Background

Statins are widely prescribed to lower cardiovascular morbidity and mortality. However, statin non-adherence is very high.

他汀类药物引起肝功能异常的系统评价

目的:系统评价他汀类药物引起肝功能异常的风险。方法:计算机检索中国生物医学文献数据库、中国期刊全文数据库、万方数据库、PubMed、EMBase、Medline、Cochrane Library、康健数据库中有关他汀类药物引起肝功能异常的随机对照试验(RCT),评价纳入研究的文献质量,提取有效数据后,采用Rev Man 5.0统计软件对数据进行Mate分析。结果:共纳入9项研究,合计9 084例患者。研究包含药物有辛伐他汀、阿托伐他汀、氟伐他汀、瑞舒伐他汀、洛伐他汀。Meta分析结果显示,使用他汀类药物治疗的患者肝功能异常发生率显著高于使用安慰剂治疗的患者,差异有统计学意义[OR=2.00,95%CI(1.23,3.25),P=0.005];并且他汀类药物高剂量组患者肝功能异常发生率显著高于低剂量组,差异亦有统计学意义[OR=1.84,95%CI(1.04,3.27),P=0.04]。结论:使用他汀类药物有引起患者肝功能异常的风险,且高剂量较易发生肝功能异常,临床应谨慎用药。由于纳入研究数量较少,该结论尚需大样本、高质量的RCT进一步证实。