Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.

PURPOSE: We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS: This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS: A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION: A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

Atorvastatin facilitates chemotherapy effects in metastatic triple-negative breast cancer.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) is treated mainly with chemotherapy. However, resistance frequently occurs as tumours enter dormancy. Statins have been suggested as effective against cancer but as they prolong and promote dormancy, it is an open question of whether the concomitant use would interfere with chemotherapy in primary and mTNBC. We examined this question in animal models and clinical correlations. METHODS: We used a xenograft model of spontaneous metastasis to the liver from an ectopic tumour employing a mTNBC cell line. Atorvastatin was provided to sensitise metastatic cells, followed by chemotherapy. The effects of statin usage on outcomes in women with metastatic breast cancer was assessed respectively by querying a database of those diagnosed from 1999 to 2019. RESULTS: Atorvastatin had limited influence on tumour growth or chemotherapy effects in ectopic primary tumours. Interestingly, atorvastatin was additive with doxorubicin (but not paclitaxel) when targeting liver metastases. E-cadherin-expressing, dormant, breast cancer cells were resistant to the use of either statins or chemotherapy as compared to wild-type cells; however, the combination of both did lead to increased cell death. Although prospective randomised studies are needed for validation, our retrospective clinical analysis suggested that patients on statin treatment could experience prolonged dormancy and overall survival; still once the tumour recurred progression was not affected by statin use. CONCLUSION: Atorvastatin could be used during adjuvant chemotherapy and also in conjunction with metastatic chemotherapy to reduce mTNBC cancer progression. These preclinical data establish a rationale for the development of randomised studies.

Adjuvant Low-dose Statin Use after Radical Prostatectomy: The PRO-STAT Randomized Clinical Trial.

PURPOSE: Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy. PATIENTS AND METHODS: In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels. RESULTS: From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58-1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan-Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71-1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels. CONCLUSIONS: Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836).See related commentary by Murtola and Siltari, p. 4947.

Grape seed extract improved the fertility-enhancing effect of atorvastatin in high-fat diet-induced testicular injury in rats: involvement of antioxidant and anti-apoptotic effects.

OBJECTIVES: Reduced male fertility is highly prevalent with hypercholesterolaemia. Though statins are drugs of choice for hypercholesterolaemia, their effect on male fertility is still controversial and dose-dependent. Grape seed extract (GSE) possess hypocholesterolemic and testicular protective effects. Thus, this study aimed to investigate the effects of low-dose atorvastatin (ATV) on male infertility in hypercholesterolaemic rats and assess the additional value of combining ATV with GSE. METHODS: Male rats were randomized into four groups. The normal group was fed a standard diet. The remaining groups were fed a high-fat diet (HFD) for 1 month to induce hypercholesterolaemia. Two HFD groups were administered either ATV (1 mg/kg) alone or combined with GSE (200 mg/kg) orally for 65 days, while the third group served as HFD control. KEY FINDINGS: Treatment with ATV or ATV/GSE attenuated dyslipidemia-induced alteration in serum HDL-cholesterol, LDL-cholesterol, and total cholesterol. ATV enhanced serum testosterone, sperm count and motility and fertility index. The effect on testosterone and sperm count was more pronounced by ATV/GSE. Moreover, ATV reduced testicular malondialdehyde, nitric oxide, caspase-9 and caspase-3 while elevated reduced glutathione and superoxide dismutase along with catalase activity. Noteworthy, GSE/ATV induced more powerful antioxidant and anti-apoptotic effects. CONCLUSION: GSE enhanced ATV's protective effect against hypercholesterolaemia-induced infertility via antioxidant and anti-apoptotic mechanisms.

Evaluation of coenzyme Q10 combined with or without N-acetyl cysteine or atorvastatin for preventing contrast-induced kidney injury in diabetic rats.

Combined antioxidants effect for prevention of contrast-induced nephropathy (CIN) remains unclear. This study assessed the potential protective effects of coenzyme Q10 (CoQ10) alone or combined with N-acetyl cysteine (NAC) or atorvastatin against CIN in diabetic rats. Animals were randomly divided into five groups, including control and four disease groups with CIN and diabetes. Group 2 included diabetic rats with CIN. Groups 3-5 included diabetic rats that received CoQ10, CoQ10 and NAC, or CoQ10 and atorvastatin, respectively, before CIN induction. Serum, urine, and tissue were collected to evaluate renal protective effects of tested agents. Renal biomarkers, oxidative stress, and histopathological alterations were investigated. Rats with CIN showed significant renal impairment as revealed by the deleterious effects on kidney function and histology. While induction of CIN did not affect the renal levels of catalase, glutathione peroxidase (GPx), and thiobarbituric acid reactive substances, pretreatment of animals with CoQ10/NAC showed significant increase in GPx and catalase levels versus controls. Lastly, pretreatment with CoQ10/atorvastatin showed regenerative effect on distal tubules with mild kidney histology alterations relative to CIN rats. The combined use of CoQ10/atorvastatin could be a potential strategy to prevent CIN. However, future studies are warranted to test different combinations for longer prophylactic periods.

Systematic evaluation of rationally chosen multitargeted drug combinations: a combination of low doses of levetiracetam, atorvastatin and ceftriaxone exerts antiepileptogenic effects in a mouse model of acquired epilepsy.

Epileptogenesis, the gradual process that leads to epilepsy after brain injury or genetic mutations, is a complex network phenomenon, involving a variety of morphological, biochemical and functional brain alterations. Although risk factors for developing epilepsy are known, there is currently no treatment available to prevent epilepsy. We recently proposed a multitargeted, network-based approach to prevent epileptogenesis by rationally combining clinically available drugs and provided first proof-of-concept that this strategy is effective. Here we evaluated eight novel rationally chosen combinations of 14 drugs with mechanisms that target different epileptogenic processes. The combinations consisted of 2-4 different drugs per combination and were administered systemically over 5 days during the latent epileptogenic period in the intrahippocampal kainate mouse model of acquired temporal lobe epilepsy, starting 6 h after kainate. Doses and dosing intervals were based on previous pharmacokinetic and tolerability studies in mice. The incidence and frequency of spontaneous electrographic and electroclinical seizures were recorded by continuous (24/7) video linked EEG monitoring done for seven days at 4 and 12 weeks post-kainate, i.e., long after termination of drug treatment. Compared to vehicle controls, the most effective drug combination consisted of low doses of levetiracetam, atorvastatin and ceftriaxone, which markedly reduced the incidence of electrographic seizures (by 60%; p<0.05) and electroclinical seizures (by 100%; p<0.05) recorded at 12 weeks after kainate. This effect was lost when higher doses of the three drugs were administered, indicating a synergistic drug-drug interaction at the low doses. The potential mechanisms underlying this interaction are discussed. We have discovered a promising novel multitargeted combination treatment for modifying the development of acquired epilepsy.

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BACKGROUND: High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. MATERIALS AND METHODS: T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of ß-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. CONCLUSION: Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Protective effects of Naoxintong capsule alone and in combination with ticagrelor and atorvastatin in rats with Qi deficiency and blood stasis syndrome.

CONTEXT: Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. OBJECTIVE: This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). MATERIALS AND METHODS: Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1ß, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. RESULTS: NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). CONCLUSIONS: The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

Intra-articular hyaluronic acid injection vs. atorvastatin; which treatment is more effective in controlling symptoms of knee osteoarthritis? A clinical trial.

BACKGROUND: Knee osteoarthritis is a disease of the elderly population. Two of the widely used treatment options for knee osteoarthritis is administration of oral atorvastatin and intra articular hyaluronic acid. This study was designed to compare the effects of oral atorvastatin and intra articular Hyaluronic acid in patients with knee osteoarthritis. METHOD: This study was conducted under the approval of Mashhad University of medical sciences ethic committee. Seventy patients with knee OA were divided randomly into two groups; thirty five subjects were given intra articular Hyaluronic acid injections weekly for three weeks and 35 were given atorvastatin 40 milligrams orally daily for 6 months. WOMAC questioner was filled for each patient at the beginning of the study and every month up to 6 months. Data were analyzed with SPSS version 16. RESULTS: Enrolled subjects were consisted of 28 males (40%) and 42 females (60%), and their mean age was 57.9±1.1 years. Study groups were similar regarding gender and age distribution (P=0.626, P=0.710, respectively) significant difference between groups regarding sex (P=0.626). Mean age of patients was 57.9±1.1 years. Groups mean age did not differ significantly (P=0.710). According to WOMAC questionnaire, pain score in the second month after injection was significantly lower in the Hyaluronic acid group compared with atorvastatin (P<0.001). Function score in the second month after injection was significantly lower in the Hyaluronic acid group compared with atorvastatin (P<0.001). These differences were absent in the following months. CONCLUSION: Compared to atorvastatin group, significant improvements in pain symptoms and physical function of knee OA patients were observed in intra articular Hyaluronic acid treatment group in the second month after treatment. But this improvement did not last through the following months.

Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer.

Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.

Association of in-hospital intensive statins dosage and death in arteriosclerotic cardiovascular disease with percutaneous coronary intervention: insights of multicentre cohort from China.

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.

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.

Development of a thermosensitive statin loaded chitosan-based hydrogel promoting bone healing.

Statins have been proposed as potential adjuvant to periodontal treatment due to their pleiotropic properties. A new thermosensitive chitosan hydrogel loaded with statins (atorvastatin and lovastatin) nanoemulsions was synthesized to allow a spatially controlled local administration of active compounds at lesion site. Spontaneous nano-emulsification method was used to synthesize statins loaded nanoemulsions. In vitro, atorvastatin and lovastatin loaded nanoemulsions were cytocompatible and were able to be uptake by oral epithelial cells. Treatment of Porphyromonas gingivalis infected oral epithelial cells and gingival fibroblasts with atorvastatin and lovastatin loaded nanoemulsions decreased significantly pro-inflammatory markers expression (TNF-α and IL-1ß) and pro-osteoclastic RANKL. Nevertheless, such treatment induced the expression of Bone sialoprotein 2 (BSP2) in osteoblast emphasizing the pro-healing properties of atorvastatin and lovastatin nanoemulsions. In vivo, in a calvarial bone defect model (2 mm), treatment with the hydrogel loaded with atorvastatin and lovastatin nanoemulsions induced a significant increase of the neobone formation in comparison with systemic administration of statins. This study demonstrates the potential of this statins loaded hydrogel to improve bone regeneration and to decrease soft tissue inflammation. Its use in the specific context of periodontitis management could be considered in the future with a reduced risk of side effects.

Severe statin-induced autoimmune myopathy successfully treated with intravenous immunoglobulin.

Statin-induced autoimmune necrotising myopathy causes a severe progressive muscle weakness even when the statins are discontinued. First-line treatment is usually with high dose steroids followed by immunosuppressants, but this is often ineffective and there is a high risk of side effects. We describe a diabetic patient who had a very severe statin-induced autoimmune myopathy. He made a full recovery with regular intravenous immunoglobulin (IVIg) infusion in relatively low dose (55 g the first day followed by 50 g/day the second and third day, subsequently he was given 50 g/day for 3 days every 6 weeks). His symptoms relapsed when the IVIgs were discontinued for 28 weeks but remitted again following recommencement of IVIg infusions (50 g/day for 3 days every 7 weeks). Our case suggests IVIgs are an effective and well tolerated alternative to steroids and immunosuppressants.

Effective atherosclerotic plaque inflammation inhibition with targeted drug delivery by hyaluronan conjugated atorvastatin nanoparticles.

Atherosclerosis is associated with inflammation in the arteries, which is a major cause of heart attacks and strokes. Reducing the extent of local inflammation at atherosclerotic plaques can be an attractive strategy to combat atherosclerosis. While statins can exhibit direct anti-inflammatory activities, the high dose required for such a therapy renders it unrealistic due to their low systemic bioavailabilities and potential side effects. To overcome this, a new hyaluronan (HA)-atorvastatin (ATV) conjugate was designed with the hydrophobic statin ATV forming the core of the nanoparticle (HA-ATV-NP). The HA on the NPs can selectively bind with CD44, a cell surface receptor overexpressed on cells residing in atherosclerotic plaques and known to play important roles in plaque development. HA-ATV-NPs exhibited significantly higher anti-inflammatory effects on macrophages compared to ATV alone in vitro. Furthermore, when administered in an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis following a 1-week treatment regimen, HA-ATV-NPs markedly decreased inflammation in advanced atherosclerotic plaques, which were monitored through contrast agent aided magnetic resonance imaging. These results suggest CD44 targeting with HA-ATV-NPs is an attractive strategy to reduce harmful inflammation in atherosclerotic plaques.

Therapeutic lifestyle change intervention improved metabolic syndrome criteria and is complementary to amlodipine/atorvastatin.

AIMS: To examine whether addition of amlodipine (5 mg)/atorvastatin (10 mg) A/A to Therapeutic Lifestyle change intervention (TLC) would beneficially modulate Metabolic Syndrome (MetS) and oxidized low-density lipoprotein (Ox-LDL) levels. METHODS: Patients with MetS (n = 53) were randomized to TLC + placebo or TLC + A/A for 12 months. Anthropometric measurements, blood pressure (BP), lipid profile, plasma Ox-LDL, and area under the curve of free fatty acid (AUCFFA) during oral glucose tolerance test, a marker of adipose tissue health, were assessed before and after the intervention. RESULTS: Twenty-six patients completed the study with an overall improvement of MetS (p = 0.02). TLC + placebo was beneficial in reversing MetS comparable to TLC + A/A (54% vs. 39%; p = 0.08). Both treatments decreased systolic BP (p ≤ 0.01). TLC + A/A also decreased diastolic BP and triglyceride levels. The changes in Ox-LDL levels directly correlated with changes in weight in the TLC-placebo group (r = 0.64; p = 0.04). AUCFFA determined the loss of fat mass (r = 0.472, p = 0.03). CONCLUSIONS: 1) Addition of A/A has the advantage of improving the lipid profile and BP; but TLC alone was comparable to TLC + A/A in improving MetS; 2) weight change determines the TLC-associated change in Ox-LDL levels; and 3) AT metabolic health is a significant predictor of TLC-associated loss of body fat mass.

Effect of high-dose strong statin for preventing periprocedural ischemic complications of carotid artery stenting.

Statin therapy has been shown to induce carotid atherosclerotic plaque regression and reduce the periprocedural ischemic complications of carotid artery stenting (CAS). This study assessed the safety and usefulness of pretreatment using a high-dose strong statin (HDSS) to reduce the periprocedural ischemic complications of CAS. We analyzed 117 carotid lesions treated by CAS that were evaluated with magnetic resonance imaging (MRI) within 48 h after the procedure. For 67 lesions, an HDSS (rosuvastatin 20 mg or atorvastatin 40 mg daily) were prescribed from at least 14 days before CAS to at least 14 days after procedure (HDSS group). Clinical and angiographic data, as well as in-hospital outcomes, of the HDSS group were retrospectively compared with 50 lesions with conventional treatment without an HDSS (non-HDSS group). There were no significant differences in the baseline clinical and procedural characteristics between the two groups. There was no side effect related to the HDSS. Stroke rates were similar between the two groups (3.0% in HDSS group vs 8.0% in non-HDSS group, p = 0.22). All were minor strokes. Compared to the non-HDSS group, the HDSS group had a lower frequency of new lesions on diffusion-weighted imaging (DWI) with MRI (25.4% vs 44.0%, p = 0.0345). New ipsilateral DWI-positive rate in the HDSS group was significantly lower than in the non-HDSS group (16.4% vs 34.0%, p = 0.0275). Nonipsilateral (contralateral or posterior circulation) DWI-positive rates were similar between the two groups (13.4% vs 20.0%, p = 0.34). Pretreatment with an HDSS might reduce the periprocedural ischemic complications of CAS.

Drug treatment of chronic subdural hematoma.

Introduction: Chronic subdural hematoma (CSDH) is a common neurosurgical disease, whose incidence has been steadily increasing with our aging population. While not common, CSDH can also occur in children. CSDH is often associated with traumatic head injury, but its underlying mechanism remains poorly understood. The first line treatment for CSDH is surgery. However, surgery is contraindicated in some patients and has a high rate of recurrence. Effective non-surgical treatment is therefore highly desirable.Areas covered: This review discusses the pathogenesis of CSDH and drugs that have been used to treat CSDH either as monotherapy or an adjuvant to surgery, including controlled clinical trials.Expert opinion: The pathophysiology of CSDH remains poorly understood. Developing effective drug treatments is therefore challenging. Most drugs discussed in this review are evaluated in small clinical studies without sufficient sample size and controls for confounding variables. More controlled clinical trials are therefore needed to carefully evaluate drugs for the non-surgical treatment of CSDH, especially for drugs targeting specific pathogenic pathways of CSDH.

Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (-29.8% vs. 3.6%, P<0.001) and non-HDL-C (-10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.