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Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies.
Lee, S, Yang, S, Chang, MJ
PloS one. 2021;(11):e0260391
Abstract
Some studies have suggested the antihypertensive effects of statins, a class of lipid-lowering agents, particularly in patients with hypertension. However, the evidence for the role of statins in blood pressure (BP) lowering is controversial, and no meta-analysis of rosuvastatin therapy has been conducted to assess its BP-lowering effects. Therefore, the aim of this meta-analysis of randomized controlled trials (RCTs) was to investigate the effects of rosuvastatin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. We systematically searched the electronic databases MEDLINE, EMBASE, and Cochrane Library to identify RCTs in which patients were assigned to groups of rosuvastatin plus antihypertensive agents vs. antihypertensive agents. The three authors independently selected the studies, extracted data, and assessed methodological quality. We included five RCTs in this meta-analysis with 288 patients treated with rosuvastatin and 219 patients without rosuvastatin. The mean DBP in the rosuvastatin group was significantly lower than that in the non-rosuvastatin group by -2.12 mmHg (95% confidence interval (CI) -3.72 to -0.52; Pfixed-effects model = 0.009; I2 = 0%, Pheterogeneity = 0.97). Rosuvastatin treatment also lowered the mean SBP compared with the non-rosuvastatin treatment by -2.27 mmHg, but not significantly (95% CI - 4.75 to 0.25; Pfixed-effects model = 0.08; I2 = 0%, Pheterogeneity = 0.82). In this study, we reviewed the antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia. We demonstrated a modest significant reduction of DBP and a trend toward a lowered SBP in patients with hypertension with rosuvastatin therapy. Rosuvastatin could be beneficial to control hypertension and, consequently, contribute toward reducing the risk of cardiovascular events in patients with hypertension and dyslipidemia.
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Evaluation of the Effects of Repeat-Dose Dabrafenib on the Single-Dose Pharmacokinetics of Rosuvastatin (OATP1B1/1B3 Substrate) and Midazolam (CYP3A4 Substrate).
Nebot, N, Won, CS, Moreno, V, Muñoz-Couselo, E, Lee, DY, Gasal, E, Bouillaud, E
Clinical pharmacology in drug development. 2021;(9):1054-1063
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Dabrafenib is an oral BRAF kinase inhibitor approved for the treatment of various BRAF V600 mutation-positive solid tumors. In vitro observations suggesting cytochrome P450 (CYP) 3A induction and organic anion transporting polypeptide (OATP) inhibition prompted us to evaluate the effect of dabrafenib 150 mg twice daily on the pharmacokinetics of midazolam 3 mg (CYP3A substrate) and rosuvastatin 10 mg (OATP1B1/1B3 substrate) in a clinical phase 1, open-label, fixed-sequence study in patients with BRAF V600 mutation-positive tumors. Repeat dabrafenib dosing resulted in a 2.56-fold increase in rosuvastatin maximum observed concentration (Cmax ), an earlier time to Cmax , but only a 7% increase in area under the concentration-time curve from time 0 (predose) extrapolated to infinite time. Midazolam Cmax and AUC extrapolated to infinite time decreased by 47% and 65%, respectively, with little effect on time to Cmax . No new safety findings were reported. Exposure of drugs that are CYP3A4 substrates is likely to decrease when coadministered with dabrafenib. Concentrations of medicinal products that are sensitive OATP1B1/1B3 substrates may increase during the absorption phase.
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Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.
Ogasawara, K, Wood-Horrall, RN, Thomas, M, Thomas, M, Liu, L, Liu, M, Xue, Y, Surapaneni, S, Carayannopoulos, LN, Zhou, S, et al
Cancer chemotherapy and pharmacology. 2021;(6):941-952
Abstract
INTRODUCTION Fedratinib, an oral, selective Janus kinase 2 inhibitor, has been shown to inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 2, and multidrug and toxin extrusion (MATE) 1 and MATE2-K in vitro. The objective of this study was to evaluate the influence of fedratinib on the pharmacokinetics (PK) of digoxin (P-gp substrate), rosuvastatin (OATP1B1/1B3 and BCRP substrate), and metformin (OCT2 and MATE1/2-K substrate). METHODS In this nonrandomized, fixed-sequence, open-label study, 24 healthy adult participants received single oral doses of digoxin 0.25 mg, rosuvastatin 10 mg, and metformin 1000 mg administered as a drug cocktail (day 1, period 1). After a 6-day washout, participants received oral fedratinib 600 mg 1 h before the cocktail on day 7 (period 2). An oral glucose tolerance test (OGTT) was performed to determine possible influences of fedratinib on the antihyperglycemic effect of metformin. RESULTS Plasma exposure to the three probe drugs was generally comparable in the presence or absence of fedratinib. Reduced metformin renal clearance by 36% and slightly higher plasma glucose levels after OGTT were observed in the presence of fedratinib. Single oral doses of the cocktail ± fedratinib were generally well tolerated. CONCLUSIONS These results suggest that fedratinib has minimal impact on the exposure of P-gp, BCRP, OATP1B1/1B3, OCT2, and MATE1/2-K substrates. Since renal clearance of metformin was decreased in the presence of fedratinib, caution should be exercised in using coadministered drugs that are renally excreted via OCT2 and MATEs. TRIAL REGISTRATION Clinicaltrials.gov NCT04231435 on January 18, 2020.
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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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Evaluation of efficacy and safety of combined rosuvastatin and atorvastatin in treating with coronary heart disease: A protocol for systematic review and meta-analysis.
Li, K, Liu, MM, Yang, X, Chen, L, Geng, H, Luo, W, Ma, J
Medicine. 2021;(24):e26340
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BACKGROUND Globally, coronary heart disease (CHD) is a primary cause of morbidity leading to disabilities and mortality. Modern clinical practice adopts several pharmacological methods to treat CHD. Angina pectoris refers to sever chest pain due to CHD, it has a profound impact on the wellbeing of patients. Moreover, angina pectoris is a crucial prognosis predictor. The aim of the current study is to evaluate the effectiveness and safeness of using combined rosuvastatin and atorvastatin to treat CHD patients. METHODS A systematic literature search for articles will be conducted on several electronic databases from their inception to May 2021. The search will include all randomized controlled trials examining the use of rosuvastatin in combination with atorvastatin to treat CHD patients. The databases are as follows: MEDLINE, Web of Science, the Cochrane Library, WanFang database, China National Knowledge Infrastructure, and EMBASE. A couple of authors will independently assess the eligibility, extract study data, and assess the possibility of bias. Moreover, depending on the type of data and heterogeneity of the included studies, either the Mantel-Haensel fixed-effect model or the DerSimonian-Laird random-effect model will be used to estimate the relative risk, mean differences, or standardized mean differences and 95% confidence intervals. All differences in opinion shall be decided by involving an additional author in the discussion. Lastly, the RevMan software (version: 5.3) will be used to perform sensitivity analysis, data synthesis, and risk of bias assessment. RESULTS The effectiveness and security of using rosuvastatin in combination with atorvastatin to treat CHD patients will be systematically evaluated. CONCLUSION This study will provide evidence to evaluate the efficacy and security of using a combination of rosuvastatin and atorvastatin to treat CHD patients. ETHICS AND DISSEMINATION Ethical approval will not be required since it is based on already published data. REGISTRATION NUMBER DOI 10.17605/OSF.IO/VYBDR (https://osf.io/vybdr/).
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Rhabdomyolysis and acute kidney injury induced by the association of rosuvastatin and abiraterone: A case report and review of the literature.
Ould-Nana, I, Cillis, M, Gizzi, M, Gillion, V, Hantson, P, Gérard, L
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2021;(1):216-219
Abstract
INTRODUCTION Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown. CASE REPORT We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin. MANAGEMENT AND OUTCOME Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone. DISCUSSION Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.
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Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects.
Mohamed, MF, Coppola, S, Feng, T, Camp, HS, Kim, E, Othman, AA
Clinical pharmacology in drug development. 2021;(11):1335-1344
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This phase 1, 2-part, 2-period, open-label, drug-drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once-daily doses of upadacitinib extended-release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (Cmax ) and area under the plasma concentration-time curve from time 0 to infinity (AUCinf ) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin Cmax and AUCinf was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The Cmax and AUCinf of the active metabolite ortho-hydroxyatorvastatin remained unchanged. Administration of a single 5-mg dose of rosuvastatin or a single 10-mg dose of atorvastatin had no relevant effect on upadacitinib Cmax or area under the plasma concentration-time curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.
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Effects of rosuvastatin and zoledronic acid in combination on the recovery of senile osteoporotic vertebral compression fracture following percutaneous vertebroplasty.
Li, H, Wang, Y, Wang, R, Yue, L, Chen, S, Li, C
The Journal of international medical research. 2020;(5):300060520925390
Abstract
OBJECTIVES This study analyzed the effects of rosuvastatin and zoledronic acid in combination on patient recovery following percutaneous vertebroplasty (PVP) that was performed to treat senile osteoporotic vertebral compression. METHODS Senile patients with osteoporotic vertebral compression fracture (n = 120) were included in this retrospective study, and they were classified into two groups. Those in the control group (n = 60) were treated with PVP + caltrate and those in the observation group (n = 60) received this treatment with combined zoledronic acid and rosuvastatin. Between-group comparisons were made at both pre- and post-treatment regarding bone density, type I procollagen peptide (CTX) and bone-specific alkaline phosphatase (BAP) levels, visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, and adjacent centrum refracture. RESULTS Bone density was higher and BAP and CTX levels as well as ODI and VAS scores were lower at post-treatment in the observation group compared with the control group. The refracture rate in the observation group was lower compared with the control group. CONCLUSION Treatment with a combination of rosuvastatin and zoledronic acid following PVP can improve the condition of senile osteoporotic vertebral compression fracture and patient's functional status, and it can also alleviate pain.
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A randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis.
McWilliam, SJ, Rosala-Hallas, A, Jones, AP, Shaw, V, Greenhalf, W, Jaki, T, Smyth, AR, Smyth, RL, Pirmohamed, M
Scientific reports. 2020;(1):1796
Abstract
The PROteKT study tested the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with Cystic Fibrosis (CF). This open label, parallel group, randomised controlled trial recruited children and young people aged 6 to 18 years with CF at 13 paediatric CF treatment centres in the UK. Participants were randomised equally to either receive oral rosuvastatin (10 mg once daily) or no intervention (control) throughout clinically indicated treatment with intravenous tobramycin. The primary outcome was the difference between the groups in mean fold-change in urinary Kidney Injury Molecule-1 (KIM-1). Fifty (rosuvastatin n = 23, control n = 27) participants were recruited between May 2015 and January 2017. Primary outcome data was available for 88% (rosuvastatin n = 20, control n = 24). The estimated mean treatment difference in the geometric mean-fold change of normalised KIM-1 was 1.08 (95% CI 0.87-1.35, p = 0.48). In total there were 12 adverse reactions, all mild, reported by five participants randomised to rosuvastatin, and one serious adverse event in each group. Whilst no protective effect of rosuvastatin was seen, there was a lower than expected level of nephrotoxicity in the cohort. Therefore, we can neither confirm nor refute the hypothesis that rosuvastatin protects against aminoglycoside nephrotoxicity.
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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.