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This article has been cited by other articles in PMC. Abstract Rosuvastatin is a new generation HMG-CoA reductase inhibitor which exhibits some unique pharmacologic and pharmacokinetic properties. Keywords: rosuvastatin, cardiovascular risk, statins, low density lipoprotein cholesterol. Introduction Ischaemic heart disease IHD is the leading cause of mortality worldwide and constitutes a major health burden.
Table 2 Pharmacokinetics of statins. Open in a separate window. Clinical Trials There have been a number of clinical studies evaluating rosuvastatin on its own, against placebo and against other statins in various clinical settings. Rosuvastatin in primary prevention Clinical studies have demonstrated the benefits of statins in primary prevention. Figure 1. Rosuvastatin in secondary prevention The beneficial effects of statin therapy in patients with ischaemic heart disease are well known.
Rosuvastatin in women Previous primary prevention trials have poorly demonstrated reduction in coronary events in women. Rosuvastatin in the elderly Randomised control trial RCT data are limited regarding statin efficacy in the elderly. Rosuvastatin in renal disease Advanced kidney disease is associated with high cardiovascular morbidity and death. Rosuvastatin in diabetes Type 2 diabetes is associated with increased risk of coronary heart disease. Rosuvastatin in children Studies in children with heterozygous FH have shown the safety and efficacy of statins, including their effect on carotid intima thickness and arterial flow mediated dilation.
Table 4 Adverse outcomes of statins. Table 5 Rosuvastatin drug interactions. Table 6 Efficacy of statins. Intermittent rosuvastatin Several small studies have reported that alternate-day therapy with rosuvastatin has important benefits in addition to improving the lipid profile.
Combination therapy Very high risk patients or those with severe dyslipidaemia often require combination therapy to achieve treatment goals and enhance lipid profile modification. Cost effectiveness Economic evaluations show that intensive lipid lowering is a cost effective treatment for very high risk patients groups including those with ACS, heterozygous FH and diabetes.
Place in Therapy Rosuvastatin is a potent statin with pharmacologic and pharmacokinetic advantages. Special groups Patients with hereditary hyperlipidaemia, particularly FH and FCH should be considered for early treatment with rosuvastatin. Disclosures Author s have provided signed confirmations to the publisher of their compliance with all applicable legal and ethical obligations in respect to declaration of conflicts of interest, funding, authorship and contributorship, and compliance with ethical requirements in respect to treatment of human and animal test subjects.
References 1. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. High density lipoprotein as a protective factor against coronary heart disease. The Framingham study. Am J Med. White CM, et al. US Pharmacist. Heart Protection Study Collaborative Group. Primary prevention of cardiovascular disease with atorvastatinin type 2 diabetes in the Collaborative Atorvastatin Diabetes Study CARDS : multicentre randomized placebo-controlled trial.
Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the ALLIANCE study. J Am Coll Cardiol. Durrington PN. Hyperlipidemia: diagnosis and management.
Hodder Arnold; London: The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs.
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in patients with coronary heart disease: the Scandinavian Simvastatin Survival Study 4S Lancet. Treating to New Targets TNT Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?
Am J Cardiol. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 participants in 14 randomised trials of statins.
White CM. Connecticut Medicine. A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. J Clin Pharmacol. AstraZeneca Pharmaceuticals LP. Crestor rosuvastatin calcium prescribing information. Wilmington: DE; McTaggart F. Comparative pharmacology of rosuvastatin. Istvan ES, Deisenhofer J. Selectivity of ZD for inhibition of cholesterol synthesis in hepatic versus non-hepatic cells.
Effects of lovastatin therapy on very-low-density lipoprotein triglyceride metabolism in subjects with combined hyperlipidemia: evidence for reduced assembly and secretion of triglyceride- rich lipoproteins. Rosuvastatin is superior to atorvastatin in decreasing low density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol in patients with type IIa or IIb hypercholesterolemia.
Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. Phenotype-dependent and— independent actions of rosuvastatin on atherogenic lipoprotein subfractions in hyperlipidaemia. Preclinical and clinical pharmacology of rosuvastatin, a new 3-hydroxymethylglutaryl coenzyme A reductase inhibitor. Rosuvastatin upregulates the antioxidant defense protein heme oxygenase Biochem Biophys Res Commun.
Int J Clin Pharmacol Ther. The HMG-CoA reductase inhibitor rosuvastatin inhibits plasminogen activator inhibitor-1 expression and secretion in human adipocytes. Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers.
Br J Clin Pharmacol. Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther. Soran H, Durrington P. Rosuvastatin efficacy, safety and clinical effectiveness. Expert Opin Pharmacother. Primary prevention of cardiovascular disease with pravastatin in Japan MEGA Study : a prospective randomised controlled trial.
C-reactive protein levels and outcomes after statin therapy. N Engl J Med. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
Koenig W, Ridker PM. Eur Heart J. Shepherd J, et al. Randomised trial of cholesterol lowering in patients with coronary heart disease: the scandinavian simvastatin survival study. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. High-dose atorvastatin vs. European guidelines on cardiovascular disease prevention in clinical practice: executive summary.
Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice constituted by representatives of nine societies and by invited experts Eur J Cardiovasc Prev Rehabil. Clearfield MB, Amerena J, et al. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hyperc holesterolemia—Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin PULSAR.
Circ J. Effect of two intensive statin regimens on progression of coronary disease. Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. Arch Cardiovasc Dis. Eur J Cardiovasc Prev Rehabil. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin JUPITER and meta-analysis of women from primary prevention trials.
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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease Study of Heart and Renal Protection : a randomised placebo-controlled trial. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study 4S Diabetes Care. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes—CORALL study.
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Rosuvastatin 1. American Heart Association. Heart and Stroke Statistical Update; ; 2. Study Group. Gould AL—; 3. Gould AL et al. Circulationet al.
Circulation ;;— Meta-analysis of 38 primary and secondary prevention trials, with more than 98, patients in total 0 4 8 12 16 20 24 28 32 36 —1.
Circulation ;— 8. NIH Publication No. Am J Cardiol ;Q—12Q. Increase lipolysis of lipoprotein triglyceride via LPL. EzetimibeEzetimibe Mechanism Inhibit absorption of cholesterol from intestine.
Pharmacodynamics A decreased delivery of cholesterol to the liver. Reduction of hepatic cholesterol stores. An increased clearance of cholesterol from the blood. Cerivastatin: Non hepatoselectiveCerivastatin: Non hepatoselective Cholesterol synthesis inhibited in fibroblastsCholesterol synthesis inhibited in fibroblasts and hepatocytes at similar concentrationsand hepatocytes at similar concentrations Buckett et al. Am J Cardiol ; — Am J Cardiol ;— —20 — Am J Cardiol ;92 Suppl KK Percentage of patients with an adverse event leading to withdrawal 10 0 2 4 6 8 rosuvastatin simvastatin pravastatin Percentageofpatients 1 3 5 7 9 2.
Brewer HB. Data on File Please refer to local Prescribing Information N Engl J Med. Shepherd J et al. Thanks for your attention! According to WHO estimates, References 1. The World Health Report, Cardiovascular Diseases — Prevention and Control.
Some of the risk factors that predispose an individual to the development or progression of CHD are outlined above. Raised blood pressure has been found to be an important risk factor for the development of CHD, cardiac failure and cerebrovascular disease. The greater the increase in blood pressure, the higher the risk. Greatest benefit of blood pressure lowering is seen in those at higher risk.
Even modest reductions produce substantial benefits in those with multiple risk factors. Dyslipidaemia, in particular, raised low-density lipoprotein LDL cholesterol and triglyceride levels, and low high-density lipoprotein HDL cholesterol are associated with increased risk of CHD.
Eur Heart J ; — Multiple risk factors for CHD are usually present in an individual; rarely do they occur in isolation. When risk factors co-exist the effect is often compounded and their combined effect is greater than the sum of their individual effects. Poulter N. Radcliffe Medical Press, Oxford, Deedwania PC. Similar reductions were seen with all lipid-modifying treatments studied. Thus, total cholesterol is a modifiable risk factor for CHD and total mortality.
Heart and Stroke Statistical Update; Eur Heart J ;— Circulation ;— National Cholesterol Education Program. Circulation ;98 3 — Large-scale intervention trials have shown a clear relationship between reduction of cholesterol by any means and reduction in both mortality, due to coronary heart disease, and total mortality. This kind of data has driven guideline bodies to more aggressive recommendations for treatment.
Reference 1. The results provide valuable insight into what is actually happening in practice and highlight that Many Patients in need of lipid lowering Therapy Remain Untreated. Reference: Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries. Euro Heart J ; Even when patients are treated, many are still not getting to goal. Of the patients who were up-titrated, two thirds never reached treatment goals despite the up-titration.
Reference: 1. Simpson RJ. The results from on-going trials should answer questions of whether further reductions in LDL-C will provide additional benefit. Adapted from Ballantyne CM. The degree of risk should indicate the severity of intervention. Less aggressive intervention may be warranted if fewer risk factors are present. JAMA ; — Statins, or HMG-CoA reductase inhibitors, are the most recently introduced class of lipid-lowering therapies and the most widely prescribed.
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