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1.
Effect of different types of statins on kidney function decline and proteinuria: a network meta-analysis.
Esmeijer, K, Dekkers, OM, de Fijter, JW, Dekker, FW, Hoogeveen, EK
Scientific reports. 2019;(1):16632
Abstract
Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We performed a network meta-analysis of randomized controlled trials (RCT) to investigate which statin most effectively reduces kidney function decline and proteinuria. We searched MEDLINE, Embase, Web of Science, and the Cochrane database until July 13, 2018, and included 43 RCTs (>110,000 patients). We performed a pairwise random-effects meta-analysis and a network meta-analysis according to a frequentist approach. We assessed network inconsistency, publication bias, and estimated for each statin the probability of being the best treatment. Considerable heterogeneity was present among the included studies. In pairwise meta-analyses, 1-year use of statins versus control reduced kidney function decline by 0.61 (95%-CI: 0.27; 0.95) mL/min/1.73 m2 and proteinuria with a standardized mean difference of -0.58 (95%-CI:-0.88; -0.29). The network meta-analysis for the separate endpoints showed broad confidence intervals due to the small number available RCTs for each individual comparison. In conclusion, 1-year statin use versus control attenuated the progression of kidney function decline and proteinuria. Due to the imprecision of individual comparisons, results were inconclusive as to which statin performs best with regard to renal outcome.
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2.
2019 Taiwan Society of Lipids and Atherosclerosis expert consensus statement on statin intolerance.
Chien, SC, Chen, PS, Huang, YH, Tang, SC, Li, YH, Yeh, HI
Journal of the Formosan Medical Association = Taiwan yi zhi. 2019;(10):1385-1392
Abstract
Statin reduces low-density lipoprotein cholesterol and improves clinical outcomes in high risk patients. In general, statin is a safe and well-tolerated medication. However, varieties of adverse effects are reported in some patients and may interfere long-term drug compliance. Statin-associated muscle events and liver function change account for most of these adverse effects. Patients are regarded as statin intolerance if they need to discontinue statin therapy due to these adverse effects. To date, there is no universal standard definition of statin intolerance. But a pragmatic definition of statin intolerance is essential and helpful for clinicians in daily practice. In this article, after expert consensus meetings and literature review, criteria were recommended to identify patients with statin intolerance in Taiwan. The purpose of this statement is to help health care professionals in Taiwan to diagnose and manage individuals who develop muscular and hepatic side effects after statin therapy.
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PRavastatin Versus FlUVastatin After Statin Intolerance: The PRUV-Intolerance Study With Propensity Score Matching.
Roh, JW, Chun, KH, Kang, M, Lee, CJ, Oh, J, Shim, CY, Ahn, CM, Kim, JS, Kim, BK, Park, S, et al
The American journal of medicine. 2019;(11):1320-1326.e1
Abstract
BACKGROUND Limited data are available on the relapse of statin intolerance after resumption of statins. We aimed to evaluate the relapse rates of statin intolerance in patients who subsequently received pravastatin or fluvastatin and to identify associated factors. METHODS This retrospective, propensity score-matched cohort study screened data obtained from a tertiary university hospital between 2006 and 2015. Of 8073 patients screened, 488 with statin intolerance who received pravastatin or fluvastatin with regular follow-up were enrolled. After propensity score matching of patients, 384 were finally analyzed. The primary outcome variables were relapse of statin intolerance and stopping (ie, discontinuation or switching to other statins) rate for the 2 statins. RESULTS During the median follow-up period of 37 months, the rate of relapse of intolerance was 10.4% and 18.2% among users of pravastatin and fluvastatin, respectively (P = 0.04). However, the log-rank test showed no difference in the relapse-free rates between the 2 groups (P = 0.34). The stopping rates of the 2 statins were 36.5% and 42.2% (P = 0.30), respectively, for various reasons, including low efficacy of the drugs. After adjustment, chronic kidney disease (hazard ratio [HR] 1.83, P = 0.03) and previous creatine kinase elevation (HR 3.13, P = 0.001) were identified as independent determinants of relapse. Older age (HR 1.03, P = 0.057) and female sex (HR 1.70, P = 0.059) were associated, but not significantly, with relapse. CONCLUSION Although a small proportion of patients taking pravastatin or fluvastatin experienced a relapse of intolerance, many patients eventually discontinued or changed these agents. Chronic kidney disease and history of creatine kinase elevation were independent determinants of relapse.
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4.
Creatine as a Candidate to Prevent Statin Myopathy.
Balestrino, M, Adriano, E
Biomolecules. 2019;(9)
Abstract
Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency might be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine; thus, they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of ATP would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of the mitochondrial permeability transition pore that is caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elderly individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.
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Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection.
El Kamari, V, Hileman, CO, Gholam, PM, Kulkarni, M, Funderburg, N, McComsey, GA
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(3):536-542.e1
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Abstract
BACKGROUND & AIMS Therapies are needed to limit progression of fatty liver diseases in patients with human immunodeficiency virus (HIV) infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults. METHODS We performed a secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 y; body mass index, 29 kg/m2; HIV1 RNA < 1000 copies/mL; low-density lipoprotein cholesterol, <130 mg/dL) receiving antiretroviral therapy. The patients were randomly assigned to groups given 10 mg daily rosuvastatin (n = 72) or placebo (n = 75). Demographic and clinical data were collected, and blood samples were analyzed. Changes in liver fat score (LFS, a composite score calculated from metabolic and liver function parameters) and markers of systemic inflammation and immune activation were assessed through 96 weeks of drug or placebo administration. We performed multivariable linear and logistic regressions to study relationships among variables. RESULTS The placebo and rosuvastatin groups each had significant increases in LFS, compared with baseline, at 96 weeks (P = .01 and P < .01; P = .49 for difference increase between groups). Baseline LFS was independently associated with blood level of C-X-C motif chemokine ligand 10 (P = .04) and the soluble CD163 molecule (P = .01). After we adjusted for baseline characteristics, an increase in LFS over time was significantly associated with the blood level of C-X-C motif chemokine ligand 10 (P = .04), insulin resistance (P < .01), and viral load (P = .02), but not rosuvastatin use (P = .06). CONCLUSIONS In a secondary analysis of data from a trial of patients receiving treatment for HIV infection, hepatic steatosis increased over time, regardless of statin treatment, and was independently associated with markers of immune activation. Patients who received rosuvastatin appeared to have a nonsignificant increase in hepatic steatosis over 96 weeks. Despite their ability to reduce the risk of cardiovascular disease, statins do not appear to reduce hepatic steatosis. Clinicaltrials.gov no: NCT01218802.
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Statin-induced muscular side effects at rest and exercise - An anatomical mapping.
Berent, T, Berent, R, Steiner, S, Sinzinger, H
Atherosclerosis. Supplements. 2019;:73-78
Abstract
BACKGROUND AND AIMS Muscle-related symptoms with or without creatine kinase (CK) elevation are common adverse effects associated with statin use. Symptoms are ranging from benign myalgia to myositis and in rare cases to rhabdomyolysis. The aim was to characterize and describe muscular side effects and create an anatomical frequency mapping. METHODS The prospective observational study was performed at a large lipidology outpatient unit in Vienna. 1111 consecutively admitted patients with muscular side effects on statin monotherapy were included during a 4-year period. Anatomical mapping of the affected muscles, signs and symptoms, the onset of symptoms after starting statin therapy and disappearance after cessation of treatment was assessed. RESULTS In 96.5% of the patients with muscle symptoms, there was no elevation of CK. The anatomical mapping revealed exercised muscles as being mainly affected in 84%. In the upper extremity, symptoms were mainly described at the dominating side. Mostly affected muscles were the pectoral (61.4%), followed by the quadriceps femoris (59.8%), the biceps brachii (54.3%) and the deltoid (22.5%) muscles. The majority of symptoms (76.9%, n = 854) appeared within 29 days. Symptoms disappeared after discontinuation of statin therapy at a mean of 5.4 days. CONCLUSIONS Physical activity seems to be a key trigger for onset of statin-induced muscular side effects. The appearance of symptoms can be symmetrical, asymmetrical, generalized or in isolated muscle groups only. Different statins usually produce similar symptoms, but often some patients tolerate one statin better than another.
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Current status of familial hypercholesterolemia in Chinese populations.
Tomlinson, B, Hu, M, Chow, E
Current opinion in lipidology. 2019;(2):94-100
Abstract
PURPOSE OF REVIEW Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations. RECENT FINDINGS The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it has been found in up to 7% of Chinese patients with premature coronary heart disease. Most of the mutations are in the low-density lipoprotein receptor gene but the pattern of mutations differs from that in Whites. Chinese patients may be more responsive to statins than Whites but patients with familial hypercholesterolemia are often undertreated. SUMMARY Increasing population cholesterol levels have changed the phenotype of familial hypercholesterolemia in China and Chinese patients now resemble those in Western countries. International initiatives are facilitating increased awareness and identification of cases and more effective management of the condition.
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Real-World Data to Identify Hypercholesterolemia Patients on Suboptimal Statin Therapy.
Kajinami, K, Ozaki, A, Tajima, Y, Yamashita, S, Arai, H, Teramoto, T
Journal of atherosclerosis and thrombosis. 2019;(5):408-431
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Abstract
AIM: Statins are generally well-tolerated but some patients develop adverse events and down-titrate or discontinue statins. It is important to understand the frequency of dyslipidemia patients with the inability to continue statins. The aim of the present study was to identify the frequency of high-risk dyslipidemia patients who are unable to take or not taking statins for any reason using Japanese hospital claims database. METHODS 2,527,405 dyslipidemia patients with atherosclerotic cardiovascular disease were investigated between April 2008 and September 2017. Definition 1 included statin discontinuation or down-titration with non-statin lipid modifying therapy (LMT) prescription, rhabdomyolysis or muscle-related symptoms with statin down-titration or discontinuation, or prescription for ≥3 statin types. Definition 2 included all components of Definition 1 in addition to statin down-titration or discontinuation for any reason. Patients never given statins but who started non-statin LMT were considered as Definition 3. The achievement rate of the target LDL-C level was investigated. RESULTS Among 54,296 patients with statin prescription, 2.32% and 48.38% patients were identified as Definition 1 and 2, respectively. Of eligible patients, 13.16% patients were identified as Definition 3. The achievement rate of target LDL-C level was lower in patients meeting each definition than not satisfying each definition. CONCLUSIONS There is a proportion of high-risk dyslipidemia patients unable to take or not taking statins for any reason, and it is associated with lower achievement rates of target LDL-C levels. Suboptimal management of LDL-C is directly associated with residual cardiovascular risk and implementation of alternative therapeutic options in addition to existing LMT is warranted.
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Prophylactic atorvastatin prior to intra-arterial administration of iodinated contrast media for prevention of contrast-induced acute kidney injury: A meta-analysis of randomized trial data
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Sun, YY, Liu, LY, Sun, T, Wu, MY, Ma, FZ
Clinical nephrology. 2019;(3):123-130
Abstract
BACKGROUND The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. OBJECTIVE This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. MATERIALS AND METHODS Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. RESULTS A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35 - 0.62, p < 0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25 - 0.66, p = 0.0003) and the placebo group (OR 0.50, 95% CI 0.26 - 0.98, p = 0.04). CONCLUSION Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.
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Statin Treatment Decreases Mitochondrial Respiration But Muscle Coenzyme Q10 Levels Are Unaltered: The LIFESTAT Study.
Dohlmann, TL, Morville, T, Kuhlman, AB, Chrøis, KM, Helge, JW, Dela, F, Larsen, S
The Journal of clinical endocrinology and metabolism. 2019;(7):2501-2508
Abstract
BACKGROUND Myalgia is a common adverse effect of statin therapy, but the underlying mechanism is unknown. Statins may reduce levels of coenzyme Q10 (CoQ10), which is an essential electron carrier in the mitochondrial electron transport system, thereby impairing mitochondrial respiratory function, potentially leading to myalgia. OBJECTIVES To investigate whether statin-induced myalgia is coupled to reduced intramuscular CoQ10 concentration and impaired mitochondrial respiratory function. METHODS Patients receiving simvastatin (i.e., statin) therapy (n = 64) were recruited, of whom 25 experienced myalgia (myalgic group) and 39 had no symptoms of myalgia (NS group). Another 20 had untreated high blood cholesterol levels (control group). Blood and muscle samples were obtained. Intramuscular CoQ10 concentration was measured, and mitochondrial respiratory function and reactive oxygen species (ROS) production were measured. Citrate synthase (CS) activity was used as a biomarker of mitochondrial content in skeletal muscle. RESULTS Intramuscular CoQ10 concentration was comparable among groups. Mitochondrial complex II-linked respiration was reduced in the statin-myalgic and -NS groups compared with the control group. When mitochondrial respiration was normalized to CS activity, respiration rate was higher in the myalgic group compared with the NS and control groups. Maximal ROS production was similar among groups. CONCLUSION Statin therapy appeared to impair mitochondrial complex-II-linked respiration, but the mitochondrial capacity for complex I+II-linked respiration remained intact. Myalgia was not coupled to reduced intramuscular CoQ10 levels. Intrinsic mitochondrial respiratory capacity was increased with statin-induced myalgia but not accompanied by increased ROS production.