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Rosuvastatin Diabetes Risk

Cholesterol-lowering Drugs May Be Linked To Diabetes

Cholesterol-lowering Drugs May Be Linked To Diabetes

You may have concerns about taking a cholesterol-lowering statin drug, such as atorvastatin (Lipitor and generic), rosuvastatin (Crestor), and simvastatin (Zocor and generic), after a recent study linked those drugs to an increased risk of type 2 diabetes. But Consumer Reports Best Buy Drugs experts say the heart-protective benefit of statins usually outweighs the risk of diabetes, so don’t skip a statin if you need one to lower your cholesterol. Diabetes isn’t a new side effect of statins. The Food and Drug Administration added it to the label of all statins in 2012 based on a review of studies that found a slightly elevated risk. For example, one study that reviewed 13 randomized, controlled clinical trials of statins found that 4.9 percent of people who took one of the drugs for 4 years developed diabetes compared with 4.5 percent of those who didn’t take a statin. Lower Cholesterol vs. Higher Blood Glucose The new study, published in the Journal of General Internal Medicine, raises questions about whether the diabetes risk is higher than previously thought. Researchers looked at medical data of nearly 7,000 men and women with an average age of 53. About 31 percent of those who took a statin for an average of 5.5 years developed diabetes compared with 19 percent of those who didn’t. But since the study was not a randomized, controlled study—the gold standard for determining whether a drug causes a particular side effect—it’s not known for sure that the increase in diabetes was entirely due to statins. The study participants might have had other factors that contributed to the development of diabetes. "All we can say," says Ishak Mansi, M.D., an internist at the Veteran's Hospital in North Texas and co-author of the study, "[is] that in the healthy popul Continue reading >>

Association Of Lipoproteins, Insulin Resistance, And Rosuvastatin With Incident Type 2 Diabetes Mellitus Secondary Analysis Of A Randomized Clinical Trial

Association Of Lipoproteins, Insulin Resistance, And Rosuvastatin With Incident Type 2 Diabetes Mellitus Secondary Analysis Of A Randomized Clinical Trial

Importance Statins decrease levels of low-density lipoprotein (LDL) and triglycerides as well as cardiovascular events but increase the risk for a diagnosis of type 2 diabetes mellitus (T2DM). The risk factors associated with incident T2DM are incompletely characterized. Objective To investigate the association of lipoprotein subclasses and size and a novel lipoprotein insulin resistance (LPIR) score (a composite of 6 lipoprotein measures) with incident T2DM among individuals randomized to a high-intensity statin or placebo. Design, Setting, and Participants This secondary analysis of the JUPITER trial (a placebo-controlled randomized clinical trial) was conducted at 1315 sites in 26 countries and enrolled 17 802 men 50 years or older and women 60 years or older with LDL cholesterol levels less than 130 mg/dL, high-sensitivity C-reactive protein levels of at least 2 mg/L, and triglyceride levels less than 500 mg/dL. Those with T2DM were excluded. A prespecified secondary aim was to assess the effect of rosuvastatin calcium on T2DM. Incident T2DM was monitored for a median of 2.0 years. Data were collected from February 4, 2003, to August 20, 2008, and analyzed (intention-to-treat) from December 1, 2013, to January 21, 2016. Interventions Rosuvastatin calcium, 20 mg/d, or placebo. Main Outcomes and Measures Size and concentration of lipids, apolipoproteins, and lipoproteins at baseline (11 918 patients with evaluable plasma samples) and 12 months after randomization (9180 patients). The LPIR score, a correlate of insulin resistance, was calculated as a weighted combination of size and concentrations of LDL, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) particles. Results Among the 11 918 patients (4334 women [36.4%]; median [interquartile range] Continue reading >>

Statin-induced Diabetes: Incidence, Mechanisms, And Implications

Statin-induced Diabetes: Incidence, Mechanisms, And Implications

Go to: Emergence of new diabetes in RCTs A clinically relevant concern with statin therapy is a significantly increased risk of new-onset diabetes in patients on statin therapy. The JUPITER trial reported a 25% increase with rosuvastatin 20 mg, over a median follow-up of 1.9 years, compared to those on placebo 9. Since then, several meta-analyses have confirmed a smaller but significant increase with various statins ( Table 1). The analysis by Sattar et al. in 91,140 subjects showed a 9% overall risk in 13 RCTs over a mean period of 4.0 years (odds ratio [OR] 1.09; 95% CI 1.02–1.17) 10. In a subsequent meta-analysis of five intensive-dose statin trials, Preiss et al. reported a significant increase in diabetes incidence with more intensive- vs. moderate-dose statin (OR 1.12; 95% CI 1.04–1.22) in 32,752 subjects over a mean follow-up of 4.9 years 11. In general, there was no relationship between % LDL-C reduction and incident diabetes. Further analysis of baseline characteristics of the various trials reported a strong relationship between features of metabolic syndrome or pre-diabetes (age, body mass index [BMI], hypertension, fasting glucose, and triglycerides) at baseline and subsequent development of diabetes 12– 14. Of note, the risk–benefit ratio for CVD still clearly favored statin therapy in various studies, including JUPITER, in primary prevention 13, several secondary prevention studies 12, 14, and a meta-analysis of secondary prevention studies by Preiss et al. 11. Thus, regardless of whether or not diabetes was diagnosed during statin therapy, the CVD outcomes were reduced on statin therapy compared to those observed with placebo. Authors n Age (years) Duration of follow-up (years) Adjusted odds ratio (95% confidence interval) Comments Sattar et al. 1 Continue reading >>

Statin Side Effects: Weigh The Benefits And Risks

Statin Side Effects: Weigh The Benefits And Risks

Statin side effects can be uncomfortable, making it seem like the risks outweigh the benefits of these powerful cholesterol-lowering medications. Doctors often prescribe statins for people with high cholesterol to lower their total cholesterol and reduce their risk of a heart attack or stroke. While statins are highly effective, they have been linked to muscle pain, digestive problems and mental fuzziness in some people and may rarely cause liver damage. Statins include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor). Having too much cholesterol in your blood increases your risk of heart attacks and strokes. Statins block a substance your liver needs to make cholesterol. This causes your liver to remove cholesterol from your blood. If you think you're experiencing side effects from statins, don't just stop taking the pills. Talk to your doctor to see if a change of dosage or even a different type of medication might be helpful. What are statin side effects? Muscle pain and damage One of the most common complaints of people taking statins is muscle pain. You may feel this pain as a soreness, tiredness or weakness in your muscles. The pain can be a mild discomfort, or it can be severe enough to make your daily activities difficult. Oddly enough, most randomized controlled studies of statins indicate that people taking statins develop muscle pain at the same rate as people taking placebo. But up to 29 percent of the people who start taking statins report muscle pain and many discontinue statins because of it. Many of these people do well when they are switched to a different variety of statin. Very rarely, statins can cause life-threatening muscle damage call Continue reading >>

Statin Induced Diabetes And Its Clinical Implications

Statin Induced Diabetes And Its Clinical Implications

Go to: INTRODUCTION “Then comes the question, how do drugs, hygiene and animal magnetism heal? It may be affirmed that they do not heal, but only relieve suffering temporarily, exchanging one disease for another”. Statins are one of the most widely prescribed groups of drugs in the world. Although statins have been shown to be beneficial in primary and secondary prevention of cardiovascular disease (CVD) in a number of trials, current reports of increased risk of type 2 diabetes with statin use are of concern. As a result of these reports, on February 28, 2012, the Food and Drug Administration added new safety label changes for the statin class of cholesterol-lowering drugs regarding the potential for increased hemoglobin A1c (HbA1c) and fasting plasma glucose. The present review discusses the evidence available from clinical trials and meta-analyses regarding possible diabetogenic effect of statins, probable mechanisms of this association and how these new observations might change clinical approach to statin use. Continue reading >>

Statin Use And Risk Of Diabetes Mellitus

Statin Use And Risk Of Diabetes Mellitus

Go to: STATINS IN DIABETES Statins are used for primary and secondary prevention of cardiovascular diseases. Other benefits due to statins are not mediated by their lipid lowering properties[8] but due to its pleiotropic effects. In conditions like heart failure, cardiac arrhythmias, vascular disease and hypertension the non-lipid lowering pleotropic benefits of statins have been observed[9]. These pleiotropic effects mediated by statins can be due to inhibition of isoprenoid synthesis which in turn inhibits intracellular signaling molecules Rho, Rac and Cdc42. The predominant mechanism that has been postulated is inhibition of Rho and its activation to Rho kinase[10]. Type 2 diabetes is characterized by hyperglycemia, insulin resistance and insulin deficiency. The insulin resistance contributes to the abnormal lipid profile associated with type 2 diabetes[11]. Dyslipidemia contributes to increased cardiovascular events in patients with type 2 diabetes[12]. A linear relationship exists between cholesterol levels and cardiovascular diseases in diabetics even if we ignore the baseline LDL[13]. By predominantly lowering LDL-Cholesterol and due to minor effects on other lipoproteins, statins appear to be beneficial[12]. In Heart Protection Study which was done in diabetics, the decrease in cardiovascular events like first major coronary event, stroke were to the tune of 22% as compared to placebo[14]. It was recommended by American Diabetes Association that statin therapy should be initiated in individuals with diabetes and other cardiovascular risk factors with target LDL cholesterol of 100 mg/dL[15]. Investigators are also of the opinion that statin therapy should depend not on the LDL levels but the cardiovascular complications accompanying diabetes[16]. Other studies wh Continue reading >>

Could Statins Raise Diabetes Risk?

Could Statins Raise Diabetes Risk?

HealthDay Reporter THURSDAY, May 23 (HealthDay News) -- Certain statins -- the widely used cholesterol-lowering drugs -- may increase your chances of developing type 2 diabetes, a new study suggests. The risk was greatest for patients taking atorvastatin (brand name Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor), the study said. Focusing on almost 500,000 Ontario residents, researchers in Canada found that the overall odds of developing diabetes were low in patients prescribed statins. Still, people taking Lipitor had a 22 percent higher risk of new-onset diabetes, Crestor users had an 18 percent increased risk and people taking Zocor had a 10 percent increased risk, relative to those taking pravastatin (Pravachol), which appears to have a favorable effect on diabetes. Physicians should weigh the risks and benefits when prescribing these medications, the researchers said in the study, which was published online May 23 in the journal BMJ. This does not, however, mean that patients should stop taking their statins, the experts said. The study also showed only an association between statin use and higher risk of diabetes; it did not prove a cause-and-effect relationship. "While this is an important study evaluating the relationship between statins and the risk of diabetes, the study has several flaws that make it difficult to generalize the results," said Dr. Dara Cohen, a professor of medicine in the department of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai in New York City. "There was no data regarding weight, ethnicity and family history -- all important risk factors for the development of diabetes." Cohen added that there was no information on the patients' cholesterol and blood sugar levels, and that higher-risk pa Continue reading >>

Risk Of Incident Diabetes Among Patients Treated With Statins: Population Based Study

Risk Of Incident Diabetes Among Patients Treated With Statins: Population Based Study

Risk of incident diabetes among patients treated with statins: population based study Risk of incident diabetes among patients treated with statins: population based study BMJ 2013; 346 doi: (Published 23 May 2013) Cite this as: BMJ 2013;346:f2610 Tara Gomes, assistant professor, scientist 2 3 4 , Muhammad M Mamdani, professor, scientist 2 3 4 6 8 1Toronto General Hospital, Toronto, ON, Canada M5G 2C4 2Leslie Dan Faculty of Pharmacy, Toronto, ON, Canada, M5S 3M2 3Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M4N 3M5 4Li Ka Shing Knowledge Institute, St Michaels Hospital, Toronto, ON, Canada, M5B 1W8 5Department of Medicine, Kings College Circle, Toronto, ON, Canada, M5S 1A8 6Department of Health Policy, Management and Evaluation University of Toronto, 155 Toronto, ON, Canada, M5T 3M6 7Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5 8Department of Medicine, St Michaels Hospital, Toronto, ON, Canada, M5B 1W8 Correspondence to: M M Mamdani mamdanim{at}smh.ca Objective To examine the risk of new onset diabetes among patients treated with different HMG-CoA reductase inhibitors (statins). Design Population based cohort study with time to event analyses to estimate the relation between use of particular statins and incident diabetes. Hazard ratios were calculated to determine the effect of dose and type of statin on the risk of incident diabetes. Participants All patients aged 66 or older without diabetes who started treatment with statins from 1 August 1997 to 31 March 2010. The analysis was restricted to new users who had not been prescribed a statin in at least the preceding year. Patients with established diabetes before the start of treatment were excluded. Results Compared with pravastatin (the reference drug in all analyses), there was an Continue reading >>

If Statins Cause Diabetes, Why Should All Diabetics Take A Statin?

If Statins Cause Diabetes, Why Should All Diabetics Take A Statin?

The guidelines from the American Heart Association and the American College of Cardiology are crystal clear. People with diabetes (both type-1 and type-2) should all be on a statin-type cholesterol-lowering medicine! There are no exceptions to this recommendation. Any physician who strays from the path of prescribing a statin to his or her diabetic patients will presumably be practicing bad medicine. What makes this guideline so intriguing is the growing body of evidence suggesting that statins cause diabetes in a substantial number of people. So, the very drug that induces elevated blood sugars is required to treat the cardiovascular risks associated with the development of drug-induced type-2 diabetes. Does this seem as odd to you as it does to us? Do Statins Cause Diabetes? Do you doubt that statins cause* diabetes? Here is just the latest research on this connection (Dormuth et al, BMJ, online, May 29, 2014). Researchers analyzed data on nearly 140,000 patients in Canada, the UK and the U.S. All the individuals had been hospitalized either because of a heart attack, stent placement or some other serious cardiovascular procedure. Some were given low-potency statins while others were placed on high-potency statins such as rosuvastatin (Crestor) at a dose of 10 mg or greater, atorvastatin (Lipitor) at a dose of 20 mg or higher or simvastatin (Zocor) at a dose of 40 mg or higher. None of the people in the analysis had been diagnosed or treated for diabetes prior to being placed on a statin. Within two years of starting on the medicine 3,629 patients were diagnosed with type-2 diabetes. Those given high-potency statins were 15% more likely to end up with blood sugar elevations compared to patients prescribed lower-potency statins or lower doses. The lead author, Colin Do Continue reading >>

Rosuvastatin Increases Diabetes Risk, Health Expert Warns

Rosuvastatin Increases Diabetes Risk, Health Expert Warns

Home Prediabetes Type 1 Type 2 Food + Recipes Living With Diabetes Treatment Complications Insurance Shop Explore Tweet Type 2 diabetes mellitus is a metabolic disorder that results in hyperglycemia (high blood glucose levels) due to the body: Being ineffective at using the insulin it has produced; also known as insulin resistance and/or Being unable to produce enough insulin Type 2 diabetes is characterised by the body being unable to metabolise glucose (a simple sugar). This leads to high levels of blood glucose which over time may damage the organs of the body. From this, it can be understood that for someone with diabetes something that is food for ordinary people can become a sort of metabolic poison. This is why people with diabetes are advised to avoid sources of dietary sugar. The good news is for very many people with type 2 diabetes this is all they have to do to stay well. If you can keep your blood sugar lower by avoiding dietary sugar, likely you will never need long-term medication. Type 2 diabetes was formerly known as non-insulin-dependent or adult-onset diabetes due to its occurrence mainly in people over 40. However, type 2 diabetes is now becoming more common in young adults, teens and children and accounts for roughly 90% of all diabetes cases worldwide. How serious is type 2 diabetes? Type 2 diabetes is a serious medical condition that often requires the use of anti-diabetic medication, or insulin to keep blood sugar levels under control. However, the development of type 2 diabetes and its side effects (complications) can be prevented if detected and treated at an early stage. In recent years, it has become apparent that many people with type 2 diabetes are able to reverse diabetes through methods including low-carb diets, very-low-calorie diets and Continue reading >>

What Statin Is Best For People With Diabetes?

What Statin Is Best For People With Diabetes?

If you have diabetes, you’re at a higher risk for heart disease and stroke. This makes it especially important to control other risk factors for cardiovascular problems, such as high cholesterol. Fortunately, there are medications called statins that are quite effective at lowering your low-density lipoprotein (LDL), or “bad” cholesterol. Which statin is most appropriate if you have diabetes? It depends on your overall cardiovascular risk, but the recommendations lean toward a moderate-intensity or high-intensity statin. There are several different types of statins. Some are more potent than others. They each work a little differently, but they all help lower cholesterol by interfering with a substance your body needs to make cholesterol in the liver. Statins have become some of the most widely prescribed medications in the world. They include atorvastatin (Lipitor), rosuvastatin (Crestor), as well as other generic and brand name versions. The optimal LDL level for most healthy people is between 70 and 100 mg/dL. If your LDL numbers exceed that range, your doctor should look at your overall heart disease and stroke risk to decide whether you should be placed on statins. Recent guidelines presented by the American College of Cardiology and the American Heart Association expanded the number of potential statin users. Doctors used to base their decision to prescribe a statin primarily on a person’s LDL score. Now, other risk factors are also considered. In general, statins are usually recommended for people who have: diagnosed cardiovascular disease an LDL cholesterol level of 190 mg/dL or higher diabetes and an LDL of 70 mg/dL or higher a 10-year heart attack risk of 7.5 percent or higher and an LDL of at least 100 mg/dL Statins and diabetes risk: What you need to Continue reading >>

Lipid-lowering Drugs And Risk Of New-onset Diabetes: A Cohort Study Using Japanese Healthcare Data Linked To Clinical Data For Health Screening

Lipid-lowering Drugs And Risk Of New-onset Diabetes: A Cohort Study Using Japanese Healthcare Data Linked To Clinical Data For Health Screening

Objective To investigate whether lipid-lowering drugs are associated with new-onset diabetes after adjusting for baseline clinical risk factors for diabetes. Setting Japanese employees of large corporations and their dependents using health insurance claims data linked to clinical and laboratory data for annual health screenings. Participants All persons aged 20 to 74 years with dyslipidaemia between 1 January 2005 and 31 March 2011. We defined the index date as the first date when the person met the criteria for dyslipidaemia. Persons were excluded if they had lipid-lowering drugs, or had a diagnosis, a treatment or a laboratory test result (haemoglobin A1c ≥6.5% or fasting blood glucose ≥126 mg/dL) indicating diabetes during the 6-month period before the index date. Results We identified 68 620 persons with dyslipidaemia. During the mean follow-up period of 1.96 years, 3674 persons started treatment with a lipid-lowering drug: 979 with a low potency statin, 2208 with a high potency statin and 487 with a fibrate. Of 3674 new users of a lipid-lowering drug, 3621 had a period of non-use of any lipid-lowering drugs before starting a lipid-lowering drug. Among statin users, the incidence rate of new-onset diabetes was 124.6 per 1000 person-years compared with 22.6 per 1000 person-years in non-users. After adjusting for confounding factors including clinical data in health screening using Cox proportional hazards models, the HR was 1.91 (95% CI 1.38 to 2.64) for low potency statins and 2.61 (2.11 to 3.23) for high potency statins. Conclusion The use of statins was associated with a 1.9-fold to 2.6-fold increase in the risk of new-onset diabetes in a Japanese population of working age, despite adjusting for clinical risk factors for diabetes. This is an Open Access artic Continue reading >>

Risk Of Diabetes With Statins

Risk Of Diabetes With Statins

TORONTO, ON The debate about the potential risks of new-onset diabetes in statin-treated patients is addressed in two separate studies published by Canadian researchers looking at patients treated with the LDL-lowering drugs[ 1 , 2 ]. While one study is reassuring for older patients treated with statins, with researchers finding no evidence of an increased risk of diabetes in acute coronary syndrome (ACS) patients, the other suggests that the more potent statins, such as rosuvastatin (Crestor, AstraZeneca), atorvastatin, and simvastatin, do pose an increased risk compared with pravastatin. In a study published online May 14, 2013 in Circulation: Cardiovascular Quality and Outcomes, Dr Dennis Ko (Sunnybrook Health Sciences Center, Toronto, ON) and colleagues explain that while clinical-practice guidelines for ACS patients advocate for the use of intensive-dose statin therapy, the data suggesting an increased risk of diabetes with the drugs have raised some concerns. The group analyzed data of more than 17 000 patients 65 years of age and older hospitalized with MI in Ontario, Canada, between 2004 and 2010. Just over 52% of the ACS patients were treated with intensive statin therapy, defined as atorvastatin >40 mg, rosuvastatin >20, and simvastatin>60 mg. Atorvastatin <40 mg, rosuvastatin <20 mg, simvastatin <60 mg, and any dose of fluvastatin, lovastatin, and pravastatin, were considered moderate-dose statin therapy and prescribed to 48% of the treated patients. In total, 8540 matched pairs who had a similar likelihood of receiving intensive-dose or moderate-dose statin therapy were included in the analysis. Five years after hospitalization for ACS, 13.6% of patients who received intensive statin therapy had a new diagnosis of diabetes. Comparatively, 13.0% of patients Continue reading >>

Statin Use Is Linked To Increased Risk Of Developing Diabetes, Warn Researchers

Statin Use Is Linked To Increased Risk Of Developing Diabetes, Warn Researchers

Statin use is linked to increased risk of developing diabetes, warn researchers Research: Risk of incident diabetes among patients treated with statins: population based study Editorial: Statins and the risk of developing diabetes Treatment with high potency statins (especially atorvastatin and simvastatin) may increase the risk of developing diabetes, suggests a paper published today on bmj.com. Statins are among the most widely prescribed medications for the prevention of cardiovascular events. Although tolerated well, an association with new-onset diabetes has recently been suggested. One trial suggested a 27% increased risk of diabetes with rosuvastatin whereas another suggested patients taking pravastatin benefitted from a 30% lower risk. As there is limited data on this subject, researchers from Canada carried out a population-based study on 1.5 million residents in Ontario, Canada to examine the association between individual statin use and new-onset diabetes. All patients were aged 66 and over and started statin therapy between 1997 and 2010. The median age was 73 years. Follow up ended either at the end of 2010 or a maximum of five years following the initiation of statins, whichever came first. The primary outcome was incident diabetes. Data were taken from the Ontario Drug Benefit database, the Canadian Institute for Health Information Discharge Abstract Database and the Ontario Diabetes Database. Statins included in the study were: fluvastatin, lovastatin, pravastatin, simvastatin, atorvastatin and rosuvastatin. All studies used pravastatin-treated patients as the comparison group as this has been shown to have favourable effects on newly diagnosed diabetes in animal models and clinical trials. 471,250 patients were identified with no history of diabetes an Continue reading >>

Rosuvastatin And Diabetes: When The Evidences Talk

Rosuvastatin And Diabetes: When The Evidences Talk

Rosuvastatin and Diabetes: When the Evidences Talk Author(s): Vivencio Barrios , Carlos Escobar . Department of Cardiology, Hospital Ramon y Cajal, Ctra. Colmenar km 9.100, 28034 Madrid, Spain. Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry Diabetes increases the risk of cardiovascular disease; however, this risk is further increased as a result of otherfactors. This observation is particularly relevant with regard to lipid abnormalities. Although diabetic dyslipidemia ischaracterized by hypertriglyceridemia, low HDL-cholesterol, and small dense LDL particles, the main determinant of therole of dyslipidemia in the prognosis of diabetics is LDL cholesterol. In recent years, LDL cholesterol targets havebecome progressively lower, and most current recommendations establish an LDL cholesterol target of <70 mg/dL fordiabetics. This target can only be achieved using potent statins at adequate doses. Although it has been suggested thatstatins may interfere with glycemic metabolism, the benefits of reducing LDL cholesterol by statins are much greater thanthis possible deleterious effect. Rosuvastatin is one of the most potent statins available. Several studies have shown that it effectively reduces LDLcholesterol to recommended targets in diabetics. Moreover, rosuvastatin modestly increases HDL cholesterol anddecreases triglycerides. The risk of side effects is low, as is the risk of interactions with other drugs. In this manuscript, the efficacy and safety profile of rosuvastatin in diabetic population is reviewed. Keywords: Diabetes, efficacy, HDL-cholesterol, LDL cholesterol, lipid profile, lipids, rosuvastatin, safety, statins, totalcholesterol, treatment, triglycerides. Cardiovascular & Hematological Agents in Medicinal Chemistry Title:Rosuvast Continue reading >>

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