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  1. Bonsu KO, Reidpath DD, Kadirvelu A
    Cardiovasc Drugs Ther, 2016 Apr;30(2):177-88.
    PMID: 26780905 DOI: 10.1007/s10557-015-6636-z
    OBJECTIVES: This study aims to compare lipophilic and hydrophilic statin therapy on clinical outcomes of heart failure (HF) using a systematic review and an adjusted indirect comparison meta-analysis. Outcomes were all-cause mortality, cardiovascular mortality, cardiovascular hospitalization and hospitalization for worsening HF.

    METHODS: We conducted a search of PubMed, EMBASE and Cochrane databases until 31st December 2014 for randomized control trials (RCTs) in HF evaluating statins versus placebo. Identified RCTs and their respective abstracted information were grouped according to statin type evaluated and analyzed separately. Outcomes were initially pooled with the Peto's one-step method, producing odd ratios (OR) and 95 % confidence intervals (CI) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons of lipophilic versus hydrophilic statin for each outcome.

    RESULTS: Thirteen studies involving 10,966 patients were identified and analyzed. Lipophilic statins were superior to hydrophilic rosuvastatin regarding all-cause mortality (OR 0 · 50; 95 % CI, 0 · 11-0 · 89; p = 0 · 01), cardiovascular mortality (OR 0 · 61; 0 · 25-0 · 97; p = 0 · 009), and hospitalization for worsening HF (OR 0 · 52; 0 · 21-0 · 83; p = 0 · 0005). However, both statins were comparable with regards to cardiovascular hospitalization [OR 0 · 80 (0 · 31, 1 · 28); p = 0 · 36].

    CONCLUSIONS: Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.

    Matched MeSH terms: Rosuvastatin Calcium/therapeutic use
  2. Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al.
    N Engl J Med, 2016 May 26;374(21):2021-31.
    PMID: 27040132 DOI: 10.1056/NEJMoa1600176
    BACKGROUND: Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease.
    METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.
    RESULTS: The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005).
    CONCLUSIONS: Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Rosuvastatin Calcium/administration & dosage*; Rosuvastatin Calcium/adverse effects
  3. Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.
    N Engl J Med, 2016 May 26;374(21):2032-43.
    PMID: 27039945 DOI: 10.1056/NEJMoa1600177
    BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
    METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
    RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
    CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Rosuvastatin Calcium/administration & dosage*; Rosuvastatin Calcium/adverse effects
  4. Garg M, Khanna D, Kalra S, Balakumar P
    Fundam Clin Pharmacol, 2016 Oct;30(5):394-405.
    PMID: 27148865 DOI: 10.1111/fcp.12204
    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.
    Matched MeSH terms: Rosuvastatin Calcium/administration & dosage*
  5. Stein EA, Dann EJ, Wiegman A, Skovby F, Gaudet D, Sokal E, et al.
    J Am Coll Cardiol, 2017 Aug 29;70(9):1162-1170.
    PMID: 28838366 DOI: 10.1016/j.jacc.2017.06.058
    BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.

    OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.

    METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.

    RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.

    CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).

    Matched MeSH terms: Rosuvastatin Calcium/administration & dosage*
  6. Bonsu KO, Owusu IK, Buabeng KO, Reidpath DD, Kadirvelu A
    J Am Heart Assoc, 2017 Apr 01;6(4).
    PMID: 28365564 DOI: 10.1161/JAHA.116.004706
    BACKGROUND: Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF.

    METHODS AND RESULTS: This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.

    CONCLUSIONS: Among Africans with HF, statin treatment was associated with significant reduction in mortality.

    Matched MeSH terms: Rosuvastatin Calcium/therapeutic use; Rosuvastatin Calcium/chemistry
  7. Al-Khateeb A, Mohamed MS, Imran K, Ibrahim S, Zilfalill BA, Yusof Z
    PMID: 21710862
    The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.
    Matched MeSH terms: Rosuvastatin Calcium
  8. Zhu JR, Tomlinson B, Ro YM, Sim KH, Lee YT, Sriratanasathavorn C
    Curr Med Res Opin, 2007 Dec;23(12):3055-68.
    PMID: 18196620
    BACKGROUND: Most studies investigating the benefits of statins have focused on North American and European populations. This study focuses on evaluating the lipid-lowering effects of rosuvastatin and atorvastatin in Asian patients.

    OBJECTIVES: The DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand.

    RESULTS: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL-C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL-C and TC. LDL-C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group.

    TRIALS REGISTRATION: The trial registry summary is available at http://www.clinicaltrials.gov/; ClinicalTrials.gov Identifier: NCT00241488

    CONCLUSIONS: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of natorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL-C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.

    Matched MeSH terms: Rosuvastatin Calcium
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