Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies

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.

Ezetimibe Improves Rosuvastatin Effects on Inflammation and Vascular Endothelial Function in Acute Coronary Syndrome Patients Undergoing PCI

Background. Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. Methods. We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. Result. The levels of sPLA2-IIa and IL-1β reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p = 0.01 ; IL-1β: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p = 0.01 ). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p = 0.03 ; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p = 0.03 ). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).

Attenuating the Variability of Lipids Is Beneficial for the Hypertension Management to Reduce the Cardiovascular Morbidity and Mortality in Older Adults

Objective: To investigate the beneficial of attenuating the variability of lipids to the hypertension management in older adults.Methods: Between April 2008 and November 2010, 1,244 hypertensive patients aged ≥60 years were recruited and randomized into placebo and rosuvastatin groups. Outcomes and inter-visit plasma lipids variability were assessed.Results: Over an average follow-up of 83.5 months, the coefficients of variation (CVs) in total cholesterol (TCHO), triglycerides, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were significantly lower in the rosuvastatin group than the placebo group (p < 0.05). The risks of composite cardiovascular event, myocardial infarction, coronary revascularization, heart failure, total stroke, ischemic stroke, cardiovascular death, and all-cause death were significantly lower in the rosuvastatin group than the placebo group (all p < 0.05). The differences in the risks were significantly diminished after the CVs for TCHO, triglycerides, HDL-c, and LDL-c were separately included as confounders. One-SD of CVs for TCHO, triglycerides, HDL-c, and LDL-c increment were significantly associated with the risks of composite cardiovascular event, myocardial infarction, heart failure, total stroke, ischemic stroke, cardiovascular death, and all-cause death, respectively (all p < 0.05).Conclusions: Rosuvastatin significantly attenuated the intra-visit variability in lipids and decreased the risk of cardiovascular mortality and morbidity. Controlling the variability of lipids is as important as antihypertensive treatment to reduce the cardiovascular morbidity and mortality in the management of older hypertensive patients.Clinical Trial Registration:ChiCTR.org.cn, ChiCTR-IOR-17013557.

Is rosuvastatin protective against sepsis associated encephalopathy? A secondary analysis of the SAILS trial

Background Sepsis is a common cause of death in emergency departments and sepsis associated encephalopathy is a major complication of sepsis. Rosuvastatin may have a cerebral protective role based on its vascular endothelial protective and anti-inflammatory functions. Our study aims to explore the potential for a protective function of rosuvastatin against sepsis associated encephalopathy. Methods Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the ‘Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome’ study (SAILS trial, ClinicalTrials.gov number, NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of this dataset. Baseline characteristics, therapy outcomes and adverse drug events were reported between groups. Outcomes: 86 patients were eligible for our study. 51 of them were treated with rosuvastatin. There were significantly fewer cases of sepsis associated encephalopathy in the rosuvastatin group than in the placebo group (32.1% vs 57.1%, p = 0.028). However, the highest CK level was significantly higher in the rosuvastatin group than in the placebo group (204.8 ± 425.31 vs 89.3 ± 78.29, p = 0.034). Conclusions Rosuvastatin is likely to have a protective role against sepsis associated encephalopathy, but may result in higher adverse events. Future large, multicenter randomized controlled trials are still needed to determine if rosuvastatin is appropriate for preventing sepsis associated encephalopathy.

Evaluating the Role of Punica Granatum and Rosuvastatin in an Experimental Model of Alzheimer’s Disease

Alzheimer’s disease is associated with progressive neurological and cognitive decline and is the commonest cause of dementia in 70% population globally. Several natural and synthetic agents are incessantly being explored as potential therapeutic targets for disease modification and treatment to reduce the suffering of the patients as well as to alleviate the huge financial burden on the healthcare system. Punica granatum contains polyphenols and flavonoids which are reported to offer neuroprotection. Statins on the other hand, serve as potent cholesterol lowering agents which target the pathophysiology of the disease. Twenty-four male wistar rats were divided into 4 groups of six rats each. They were fed high fat diet for two months.The rats in the respective groups were given Punica granatum juice, Rosuvastatin, standard treatment comprising of Donepezil and distilled water. The analysis was done at baseline and at the end of the study. Behavioral tests and histopathological analysis depicted marked improvement in cognitive and memory functions in Punica granatum group. Rosuvastatin group however showed improvement which was not as pronounced as achieved by the Punica granatum group. The present study was done to discern the effects of test agents such as Punica granatum and Rosuvastatin in memory deficits associated with Alzheimer’s disease. Marked improvement in dementia was observed in Punica granatum juice group in the High Fat Diet induced model of Alzheimer’s disease. Hence, Punica granatum offers significant neuroprotection as compared to the Rosuvastatin group and its potential can be explored in further studies to consolidate its role in amelioration of the disease progress and its treatment.

Comparison of atorvastatin and rosuvastatin on preventing contrast-induced-nephropathy in patients undergoing primary percutaneous coronary intervention: A multi-centric randomized triple-blind clinical trial

Background: Patients with Contrast-Induced-Nephropathy (CIN) are at a greater risk of in-hospital complications, longer hospitalization, and long-term mortality in comparison with those without CIN. Despite many studies on the helpful effects of statins in preventing contrast-nephropathy, there is not enough evidence comparing different statins in inhibiting CIN. So, we planned this study to compare the efficacy of rosuvastatin and atorvastatin in prevention of contrast-induced nephropathy. Methods: This was a randomized clinical trial. The efficacy of two known statins, atorvastatin and rosuvastatin were compared in prevention of CIN in patients with ST-Elevation Myocardial Infarction (STEMI) who underwent Primary Percutaneous Intervention (PPCI) between May 2015 and April 2016 in Qaem and Imam Reza hospital, Mashhad, Iran. Subjects were divided randomly to 80-mg atorvastatin or 40-mg rosuvastatin group before PPCI. Participants’ characteristics including echocardiographic, laboratory and demographic data were recorded and incidence of CIN was assessed. Results: Two hundred cases with STEMI undergoing PPCI were recruited in the study and randomized to 80-mg atorvastatin (n = 98) or 40-mg rosuvastatin (n = 102) group before PPCI. The incidence of CIN was 5.67% (n = 13) in all participants; 6.3% (n = 7) in the rosuvastatin group and 5.1% (n = 6) in the atorvastatin group. There was a significant difference between creatinine and Glomerular Filtration Rate (GFR) after 48 hours of PPCI. Creatinine was lower and GFR was higher in the rosuvastatin group (P = 0.029, P = 0.005). Conclusion: There was a little trend for prevention of CIN in patients after PPCI in rosuvastatin group compared to atorvastatin group, in full dose. However, this preference was not clinically relevant.

Comparison Between Atorvastatin and Rosuvastatin on Anti- Thrombogenic Effect in Patients with Hyperlipidemia

Background: Atorvastatin and rosuvastatin are two widely used HMG-CoA reductase inhibitors (statins). These are used as lipid-lowering drugs to reduce atherosclerosis-induced cardiovascular events. The beneficial effects of statins also involve some lipid-independent mechanisms which include modification of thrombus formation and degradation, alteration in inflammatory response, plaque stabilization and improvement of endothelial function.Objective: To compare antithrombogenic effect of atorvastatin and rosuvastatin in patients with hyperlipidemia.Materials and Methods: A prospective, open-labeled, interventional, randomized and single-center study was carried out in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from March, 2016 to August, 2017 on 52 hyperlipidemic patients. After randomization patients were assigned to atorvastatin 10 mg or rosuvastatin 5 mg daily for 8 weeks. Blood was collected at baseline and after intervention to measure platelet count, prothrombin time (PT) and serum lipid profile.Results: The baseline characteristics of patients treated with atorvastatin and rosuvastatin were almost identical. The platelet count in atorvastatin group was reduced after intervention (2.30%, p=0.463) which was not significant but in rosuvastatin group platelet count reduced significantly (12.33%, p=0.021) after intervention. There was no statistically significant difference (p=0.187) between the two statin treated groups. PT was increased significantly after intervention in both atorvastatin group (31.44%, p<0.001) and in rosuvastatin group (31.93%, p=0.003), which was statistically significant. No significant difference was observed between the two groups (p=0.573). Both atorvastatin and rosuvastatin significantly improved serum lipid profile.Conclusion: The present study reveals that rosuvastatin reduced thrombogenesis more effectively than atorvastatin in hyperlipidemic patients.J Enam Med Col 2018; 8(3): 153-158

Influence of risk factors on progression of atherosclerosis of brachiocephalic artery with un-derlying treatment with statins

Aim. Analysis of influence of risk factors (RF) on progression of atherosclerosis of brachiocephalic arteries after unilateral carotid endarterectomy (CEA) with the underlying treatment with statins. Materials and Methods. 262 Cases (262 patients) were analyzed. Influence of RFs on the frequency of cerebral circulation disorders (CCD), myocardial infarction (MI), survival rate, condition of the carotid arteries and on lipid profile with the underlying treatment with statins was evaluated. In the early period the results were evaluated in 100% of patients, in a long-term period – in 93.5%. Patients were arranged in groups: a group that received simvastatin – 41.6% in the preoperative period and 24.5% in the long-term period, a group of atorvastatin – 51.9% and 54.7%, a group of rosuvastatin – 6.5% and 20.8%, respectively. Predominating (83.2%) were patients with more than 3 RFs (according to SCORE scale). Results. Lethality rate in the analyzed sample group was 6.5%, the rate of fatal cardio-vascular complications (CVC) – 7 cases (2.3%), of non-fatal CCD – 5 cases (1.9%). A significant influence on the progression of alterations in the carotid artery was found in patients with 3 RFs (p=0.03). The length of atherosclerotic plaque (ASP) was maximal in patients with 5 RFs (0.01). In the presence of more than 3 RFs, elevation of the total cholesterol (CL) and of low density lipoproteins (LDLP) was noted, p=0.001. In the long-term period in the atorvastatin group the level of LDLP decreased by 19%, p=0.0001, in the rosuvastatin group the level of HDLP increased by 3.4%, p=0.02. In the rosuvastatin group, the recommended values of CL were achieved 64.7% more often in comparison with the simvastatin group, p=0.03. The rate of CVC increased in patients >68 years of age, р=0.04. The lethality rate increased in case of body mass index (BMI) ≥25-30 kg/m2 (р=0.05) and in case of type 2 diabetes mellitus (p=0.03). The influence of the following factors on long-term results was demonstrated: smoking (p=0.04), arterial hypertension (p=0.019), chronic cardiac insufficiency (p=0.01), a tendency to bradycardia (p=0.03), atherosclerotic lesions of more than one arterial pool (p=0.006). RFs influenced the rate of development of restenosis of the internal carotid artery (ICA) >50% on the side of the operation in 4 observations (1.5%). In the atorvastatin group the most significant positive influence on lipid spectrum was observed in comparison with other groups (by 47.1%, р=0.001).Therapy with atorvastatin stabilized the wall of ICA and of the contralateral common carotid artery (CCA) 17.6% (p=0.05) more frequently in comparison with simvastatin and rosuvastatin. Conclusion. A direct influence of RFs on the progression of atherosclerotic alterations in the carotid arteries and on the rate of development of cardiovascular complications in the perioperative and long-term periods, and also influence of underlying statin therapy on the parameters of lipid metabolism, and a higher effectiveness of synthetic statins were determined.

Influence of risk factors on progression of atherosclerosis of brachiocephalic artery with un-derlying treatment with statins

Aim. Analysis of influence of risk factors (RF) on progression of atherosclerosis of brachiocephalic arteries after unilateral carotid endarterectomy (CEA) with the underlying treatment with statins. Materials and Methods. 262 Cases (262 patients) were analyzed. Influence of RFs on the frequency of cerebral circulation disorders (CCD), myocardial infarction (MI), survival rate, condition of the carotid arteries and on lipid profile with the underlying treatment with statins was evaluated. In the early period the results were evaluated in 100% of patients, in a long-term period – in 93.5%. Patients were arranged in groups: a group that received simvastatin – 41.6% in the preoperative period and 24.5% in the long-term period, a group of atorvastatin – 51.9% and 54.7%, a group of rosuvastatin – 6.5% and 20.8%, respectively. Predominating (83.2%) were patients with more than 3 RFs (according to SCORE scale). Results. Lethality rate in the analyzed sample group was 6.5%, the rate of fatal cardio-vascular complications (CVC) – 7 cases (2.3%), of non-fatal CCD – 5 cases (1.9%). A significant influence on the progression of alterations in the carotid artery was found in patients with 3 RFs (p=0.03). The length of atherosclerotic plaque (ASP) was maximal in patients with 5 RFs (0.01). In the presence of more than 3 RFs, elevation of the total cholesterol (CL) and of low density lipoproteins (LDLP) was noted, p=0.001. In the long-term period in the atorvastatin group the level of LDLP decreased by 19%, p=0.0001, in the rosuvastatin group the level of HDLP increased by 3.4%, p=0.02. In the rosuvastatin group, the recommended values of CL were achieved 64.7% more often in comparison with the simvastatin group, p=0.03. The rate of CVC increased in patients >68 years of age, р=0.04. The lethality rate increased in case of body mass index (BMI) ≥25-30 kg/m2 (р=0.05) and in case of type 2 diabetes mellitus (p=0.03). The influence of the following factors on long-term results was demonstrated: smoking (p=0.04), arterial hypertension (p=0.019), chronic cardiac insufficiency (p=0.01), a tendency to bradycardia (p=0.03), atherosclerotic lesions of more than one arterial pool (p=0.006). RFs influenced the rate of development of restenosis of the internal carotid artery (ICA) >50% on the side of the operation in 4 observations (1.5%). In the atorvastatin group the most significant positive influence on lipid spectrum was observed in comparison with other groups (by 47.1%, р=0.001).Therapy with atorvastatin stabilized the wall of ICA and of the contralateral common carotid artery (CCA) 17.6% (p=0.05) more frequently in comparison with simvastatin and rosuvastatin. Conclusion. A direct influence of RFs on the progression of atherosclerotic alterations in the carotid arteries and on the rate of development of cardiovascular complications in the perioperative and long-term periods, and also influence of underlying statin therapy on the parameters of lipid metabolism, and a higher effectiveness of synthetic statins were determined.

A Comparative Study of Muscle Symptoms of Atorvastatin with Rosuvastatin in Patients of Atherosclerotic Cardiovascular Disease

Background: Statins are the corner stone therapy of atherosclerotic cardiovascular disease (ASCVD). Statins may cause myalgia, myotoxicity, myopathy and rhabdomyolysis along with its lipid lowering properties and pleiotropic effects. Statins associated muscle symptoms (SAMS) are the leading cause of nonadherent and discontinuation. This study was conducted to evaluate and understand the muscle symptoms of high intensity statin therapy (atorvastatin 40 mg and rosuvastatin 20 mg) for a period of three months in individual patient with clinical atherosclerotic cardiovascular disease.Methods: A total of 280 patients with clinical atherosclerotic cardiovascular disease were studied to once daily atorvastatin 40 mg and rosuvastatin 20 mg. It was a randomized controlled single blind trial. The primary end point was muscle symptoms-muscle pain, fatigue, cramp/spasticity and weakness at 4 weeks and in 3 months of study period. Serum creatinine kinase was measured in every patient with muscular symptoms.Results: Patients of atorvastatin group noticed severe pain more than rosuvastatin group at the end of 3 months of treatment period (14.21% vs 4.38%, p <0.05), respectively). Significantly more patients felt extremely bad (12.78% vs 4.38%, p <0.05) and bad (24.66% vs 14.52%, p <0.05) with atorvastatin compared with rosuvastatin. Patients of atorvastatin group showed more marked increase muscle spasm (3.76% vs 1.46%, p <0.05) and slight increase muscle spasm (36.27% vs 16.01%, p <0.05) than rosuvastatin group by spasticity grade. One patient of atorvastatin group developed considerable increase in muscle spasm. Medical research council (MRC) muscle power grade 4 between atorvastatin and rosuvastatin group was observed 20.05% vs 10.90%, p <0.05, respectively. Three patients of atorvastatin group developed grade 3 muscle power. Serum creatine kinase > 1500 U/L was observed more in atorvastatin than rosuvastatin group (14.21% vs 4.38%, p <0.05, respectively). Statin associated muscle symptoms (more severe muscle problem, myositis/myopathy) observed more in atorvastatin than that of rosuvastatin group ( 34.07% vs 13.08% , p <0.05, respectively). Both treatments were well tolerated. No cases of rhabdomyolysis, incident diabetes, hepatic or renal insufficiency were recorded during the study period.Conclusion: Rosuvastatin had better outcome profile of muscle symptoms than atorvastatin in patients with clinical atherosclerotic cardiovascular disease among the Bangladeshi population. Patients in atorvastatin group experienced more muscle pain, fatigue, cramp/spasticity and weakness than rosuvastatin.University Heart Journal Vol. 14, No. 1, Jan 2018; 9-20