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Impact of statin therapy on LDL and non-HDL cholesterol levels in subjects with heterozygous familial hypercholesterolaemia.
Climent, E, Marco-Benedí, V, Benaiges, D, Pintó, X, Suárez-Tembra, M, Plana, N, Lafuente, H, Ortega-Martínez de Victoria, E, Brea-Hernando, Á, Vila, À, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(5):1594-1603
Abstract
BACKGROUND AND AIMS Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins. METHODS AND RESULTS Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects. CONCLUSION According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.
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Concomitant Use of Rosuvastatin and Eicosapentaenoic Acid Significantly Prevents Native Coronary Atherosclerotic Progression in Patients With In-Stent Neoatherosclerosis.
Sugizaki, Y, Otake, H, Kuroda, K, Kawamori, H, Toba, T, Nagasawa, A, Takeshige, R, Nakano, S, Matsuoka, Y, Tanimura, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1826-1836
Abstract
BACKGROUND In-stent neoatherosclerosis (NA) is a risk for future cardiovascular events through atherosclerotic progression in non-stented lesions. Using optical coherence tomography, this study assessed the efficacy of intensive therapy with 10 mg/day rosuvastatin plus 1,800 mg/day eicosapentaenoic acid (EPA) vs. standard 2.5 mg/day rosuvastatin therapy on native coronary plaques in patients with NA.Methods and Results:This was a subgroup analysis of the randomized LINK-IT trial, which was designed to compare changes in the lipid index in NA between intensive and standard therapy for 12 months. In all, 42 patients with native coronary plaques and NA were assessed. Compared with standard therapy, intensive therapy resulted in greater decreases in serum low-density lipoprotein cholesterol concentrations and greater increases in serum 18-hydroxyeicosapentaenoic acid concentrations, with significantly greater decreases in the lipid index and macrophage grade in both NA (-24 vs. 217 [P<0.001] and -15 vs. 24 [P<0.001], respectively) and native coronary plaques (-112 vs. 29 [P<0.001] and -17 vs. 1 [P<0.001], respectively) following intensive therapy. Although there was a greater increase in the macrophage grade in NA than in native coronary plaques in the standard therapy group, in the intensive therapy group there were comparable reductions in macrophage grade between NA and native coronary plaques. CONCLUSIONS Compared with standard therapy, intensive therapy prevented atherosclerotic progression more effectively in native coronary plaques in patients with NA.
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To study impact of treatment with Rosuvastatin versus Atorvastatin on 25 hydroxy Vitamin D concentrations among adult Indian men- a randomized control trial.
Patwardhan, VG, Mughal, ZM, Padidela, R, Chiplonkar, SA, Khadilkar, VV, Khadilkar, AV
Indian journal of pharmacology. 2020;(5):365-371
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Abstract
BACKGROUND Dyslipidemias are on the rise and are increasingly being treated with statins. As the metabolism of cholecalciferol and cholesterol are interrelated, reduction in cholesterol synthesis by statins is likely to affect Vitamin D status. OBJECTIVES (1) The aim is to study the effect of treatment with statins (Atorvastatin/Rosuvastatin) on 25-hydroxy-Vitamin-D (25OHD) among newly detected subjects with dyslipidemia for 6 months (2) To study the impact of 25OHD concentrations on the efficacy of statin treatment. MATERIALS AND METHODS This was a prospective, balanced randomized (1:1), open-label, parallel-group study, in apparently healthy Indian adult men (south Asian, 40-60 years). At baseline, serum lipids and 25OHD concentrations were measured. Based on the Adult Treatment Panel III guidelines, subjects were divided as per lipid concentrations into controls (who did not require statin treatment) and intervention (who required statin treatment) groups. Random allocation of subjects was done in two groups for receiving intervention for 6 months: Atorvastatin group (n = 52, received Atorvastatin) or Rosuvastatin group (n = 52, received Rosuvastatin). Lipids and 25OHD concentrations were measured at the end line. RESULTS Atorvastatin group presented significant reduction (P < 0.05) in 25OHD, total cholesterol (TC) and low-density-lipoprotein-cholesterol (LDL-C) concentrations at the end line. In the Rosuvastatin group, significant drop in TC, LDL-C and high-density lipoprotein cholesterol (concentrations (P < 0.05) was observed, while 25OHD concentrations showed no significant change. Mean 25OHD concentrations were significantly correlated with a reduction in LDL-C concentrations in Atorvastatin group. CONCLUSIONS Treatment with Atorvastatin resulted in a reduction in 25OHD concentrations; further, its efficacy in reducing LDL-C concentrations was related to the 25OHD concentrations.
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Comparison between Atorvastatin and Rosuvastatin on Secondary Percutaneous Coronary Intervention Rate and the Risk Factors in Patients with Coronary Heart Disease.
Zhang, J, Wang, J, Yu, H, Wang, G, Zhang, J, Zhu, R, Liu, X, Li, J
Current drug metabolism. 2020;(10):818-828
Abstract
OBJECTIVE The aim is to compare atorvastatin versus rosuvastatin on secondary percutaneous coronary intervention (PCI) rate and explore risk factors in coronary heart disease (CHD) patients. METHODS A cohort study with 283 CHD subjects was launched from 2011 to 2015. Cox proportional hazards regression model, Receiver Operating Characteristic (ROC) and nomogram were used to compare the effect of atorvastatin and rosuvastatin on secondary PCI rate and disease risk factors. Even why the two statins had different effects based on gene expression profile analysis has been explored. RESULTS Gene FFA (Freely fatty acid), AST (Aspartate Transaminase) and ALT (Alanine transaminase) showed the statistical difference between the four statin groups (P<0.05). In the AA group (Continuous Atorvastatin usage), albumin was a risk factor (Hazard Ratio (HR):1.076, 95%CI (1.001, 1.162), p<0.05). In the AR group (Start with Atorvastatin usage, then change to Rosuvastatin usage), ApoA was a protective factor (HR:0.004, 95%CI (0.001, 0.665), p<0.05). GLB (Galactosidase Beta) was a risk factor (HR:1.262, 95%CI (1.010, 1.576), p<0.05). In RR group (Continuous Rosuvastatin usage), ApoE was a protective factor (HR:0.943, 95%CI (0.890, 1.000), <0.05). ALT was a risk factor (HR:1.030, 95%CI (1.000, 1.060), p<0.05). CONCLUSION Patients in the RA group had the lowest secondary PCI rate. ALT was a risk factor in the RR group. Gene Gpt (Glutamic Pyruvic Transaminase) encoded for one subtype of ALT had a significantly different expression in different statin groups.
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Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence.
Perez-Calahorra, S, Laclaustra, M, Marco-Benedi, V, Pinto, X, Sanchez-Hernandez, RM, Plana, N, Ortega, E, Fuentes, F, Civeira, F
Lipids in health and disease. 2019;(1):216
Abstract
BACKGROUND There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. METHODS This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. RESULTS Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. CONCLUSIONS This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD.
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Circulating microparticles and central blood pressure according to antihypertensive strategy.
Massunaga, ND, França, CN, Bianco, HT, Ferreira, CES, Kato, JT, Póvoa, RMS, Figueiredo Neto, AM, Izar, MCO, Fonseca, FAH
Clinics (Sao Paulo, Brazil). 2019;:e1234
Abstract
OBJECTIVES This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.
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A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial.
Hong, SJ, Jeong, HS, Ahn, JC, Cha, DH, Won, KH, Kim, W, Cho, SK, Kim, SY, Yoo, BS, Sung, KC, et al
Clinical therapeutics. 2018;(2):226-241.e4
Abstract
PURPOSE Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia. METHODS I-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea. Patients with hypercholesterolemia who required medical treatment according to National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for participation in the study. Patients were randomly assigned to receive ezetimibe 10 mg/rosuvastatin 20 mg, ezetimibe 10 mg/rosuvastatin 10 mg, ezetimibe 10 mg/rosuvastatin 5 mg, rosuvastatin 20 mg, rosuvastatin 10 mg, or rosuvastatin 5 mg in a 1:1:1:1:1:1 ratio. The primary end point was the difference in the mean percent change from baseline in LDL-C level after 8 weeks of treatment between the ezetimibe/rosuvastatin and rosuvastatin treatment groups. All patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS Of 396 patients, 389 with efficacy data were analyzed. Baseline characteristics among 6 groups were similar. After 8 weeks of double-blind treatment, the percent changes in adjusted mean LDL-C levels at week 8 compared with baseline values were -57.0% (2.1%) and -44.4% (2.1%) in the total ezetimibe/rosuvastatin and total rosuvastatin groups, respectively (P < 0.001). The LDL-C-lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. The mean percent change in LDL-C level in all ezetimibe/rosuvastatin combination groups was >50%. The number of patients who achieved target LDL-C levels at week 8 was significantly greater in the ezetimibe/rosuvastatin group (180 [92.3%] of 195 patients) than in the rosuvastatin monotherapy group (155 [79.9%] of 194 patients) (P < 0.001). There were no significant differences in the incidence of overall AEs, adverse drug reactions, and serious AEs; laboratory findings, including liver function test results and creatinine kinase levels, were comparable between groups. IMPLICATIONS Fixed-dose combinations of ezetimibe/rosuvastatin significantly improved lipid profiles in patients with hypercholesterolemia compared with rosuvastatin monotherapy. All groups treated with rosuvastatin and ezetimibe reported a decrease in mean LDL-C level >50%. The safety and tolerability of ezetimibe/rosuvastatin therapy were comparable with those of rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT02749994.
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Platelet tissue factor activity and membrane cholesterol are increased in hypercholesterolemia and normalized by rosuvastatin, but not by atorvastatin.
Panes, O, González, C, Hidalgo, P, Valderas, JP, Acevedo, M, Contreras, S, Sánchez, X, Pereira, J, Rigotti, A, Mezzano, D
Atherosclerosis. 2017;:164-171
Abstract
BACKGROUND AND AIMS High plasma LDL-cholesterol (LDL-C) and platelet responses have major pathogenic roles in atherothrombosis. Thus, statins and anti-platelet drugs constitute mainstays in cardiovascular prevention/treatment. However, the role of platelet tissue factor-dependent procoagulant activity (TF-PCA) has remained unexplored in hypercholesterolemia. We aimed to study platelet TF-PCA and its relationship with membrane cholesterol in vitro and in 45 hypercholesterolemic patients (HC-patients) (LDL-C >3.37 mmol/L, 130 mg/dL) and 37 control subjects (LDL-C <3.37 mmol/L). The effect of 1-month administration of 80 mg/day atorvastatin (n = 21) and 20 mg/day rosuvastatin (n = 24) was compared. METHODS Platelet TF-PCA was induced by GPIbα activation with VWF-ristocetin. RESULTS Cholesterol-enriched platelets in vitro had augmented aggregation/secretion and platelet FXa generation (1.65-fold increase, p = 0.01). HC-patients had 1.5-, 2.3- and 2.5-fold increases in platelet cholesterol, TF protein and activity, respectively; their platelets had neither hyper-aggregation nor endogenous thrombin generation (ETP). Rosuvastatin, but not atorvastatin, normalized platelet cholesterol, TF protein and FXa generation. It also increased slightly the plasma HDL-C levels, which correlated negatively with TF-PCA. CONCLUSIONS Platelets from HC-patients were not hyper-responsive to low concentrations of classical agonists and had normal PRP-ETP, before and after statin administration. However, washed platelets from HC-patients had increased membrane cholesterol, TF protein and TF-PCA. The platelet TF-dependent PCA was specifically expressed after VWF-induced GPIbα activation. Rosuvastatin, but not atorvastatin treatment, normalized the membrane cholesterol, TF protein and TF-PCA in HC-patients, possibly unveiling a new pleiotropic effect of rosuvastatin. Modulation of platelet TF-PCA may become a novel target to prevent/treat atherothrombosis without increasing bleeding risks.
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Is age an important factor for vascular response to statin therapy? A serial optical coherence tomography and intravascular ultrasound study.
Dai, J, Hou, J, Xing, L, Jia, H, Hu, S, Soeda, T, Minami, Y, Ong, D, Vergallo, R, Zhang, S, et al
Coronary artery disease. 2017;(3):209-217
Abstract
OBJECTIVE Age-related structural and functional changes in vessel wall may affect the time course of vascular response to statin therapy. In this study, we sought to compare the response of lipid-rich plaque to statin therapy in elderly versus younger patients using optical coherence tomography and intravascular ultrasound. PATIENTS AND METHODS Sixty-nine patients who underwent serial optical coherence tomography and intravascular ultrasound at the time point of baseline, 6, and 12 months were divided into two groups according to median age: group A (age<57 years, n=35) and group B (age≥57 years, n=34). Patients were treated with intensive (atorvastatin 60 mg/day) or moderate (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) statin therapy. RESULTS A continuous increase in fibrous-cap thickness (FCT) from baseline to 12 months was observed in both groups (P<0.001, <0.001, respectively). Intensive statin induced greater percent change in FCT at 12 months than moderate statin in group B (P=0.020), but not in group A (P=0.251). Mean lipid arc decreased significantly at 12 months in two groups (P<0.001, <0.001, respectively), and this response was delayed for 6 months (P=0.403) and began to decrease during the second 6 months (P<0.001) in group B. Normalized total atheroma volume decreased significantly in group A (P<0.001), but not in group B (P=0.349). CONCLUSION Statin therapy could stabilize lipid-rich plaque irrespective of age, and intensive statin therapy was more effective than a moderate dose of statin in increasing FCT, particularly in older patients. A delayed response of lipid content and unfavorable change in normalized total atheroma volume to statin were observed in elderly patients.
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Therapy with atorvastatin versus rosuvastatin reduces urinary podocytes, podocyte-associated molecules, and proximal tubule dysfunction biomarkers in patients with type 2 diabetes mellitus: a pilot study.
Vlad, A, Vlad, M, Petrica, L, Ursoniu, S, Gadalean, F, Popescu, R, Vlad, D, Dumitrascu, V, Gluhovschi, G, Gluhovschi, C, et al
Renal failure. 2017;(1):112-119
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BACKGROUND Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. METHODS A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. RESULTS The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p < .05), urinary nephrin (from 1.7 to 1.3 mg/g, p < .001), urinary vascular endothelial growth factor (from 262.8 to 256.9, p < .01), urinary alpha1-microglobulin (from 10.0 to 8.3 mg/g, p < .01), urinary kidney injury molecule-1 (from 139.5 to 136.3 ng/g, p < .001), and urinary advanced glycation end-products (from 112.6 to 101.3 pg/ml, p < .001). Podocyturia correlated directly with the podocyte damage biomarkers, proximal tubule dysfunction biomarkers, albumin to creatinine ratio, and advanced glycation end-products, and inversely with the glomerular filtration rate. CONCLUSIONS In patients with Type 2 diabetes, atorvastatin exerts favorable effects on the kidney. There is a correlation between the evolution of the podocytes and of the proximal tubule biomarkers, supporting the hypothesis that the glomerular changes parallel proximal tubule dysfunction in the early stages of diabetic nephropathy.