Current Perspectives on rosuvastatin

Figures & data

Table 1 Pharmacokinetic properties of statins

Parameters	Atorvastatin	Fluvastatin	Lovastatin	Pitavastatin	Pravastatin	Rosuvastatin	Simvastatin
Bioavailability, %	12	24–30	5	60–80	18	20	<5
Protein binding, %	>98	>98	>98	>99	50	88	>95
Half-life, hours	7–20	1–3	2–5	10–13	1–3	19	2–5
Hepatic extraction, %	70	≥70	≥70	80	45	63	≥80
Renal excretion, %	<5	6	10	15	20	10	13
Metabolism	+++	+++	+++	++	+	+	+++
CYP	3A4, 2C8	2C9	3A4/5, 2C8	2C9, 2C8	3A4	2C9, 2C19	3A4/5, 2C8
Influx transporters	SLCO1B1	SLCO1B1	SLCO1B1, SLC16A4	SLCO1B1/1B3/2B1/1A2	SLCO1B1/2B1 SLC22A8, SLC16A1	SLCO1B1/1B3/2B1/1A2 SLC10A1	SLCO1B1
Efflux transporters	ABCB1/G2	ABCG2	ABCB1	ABCB1/C2/G2	ABCB1/B11/C2/G2	ABCB1/C2/G2	ABCB1/G2

Abbreviations: ABC, ATP-binding cassette; CYP, cytochrome P450 enzymes; SLC, solute carrier; SLCO, solute carrier organic anion transporter.

Notes: “+” indicates the drug undergoes metabolism; the number of “+” indicates the extent of metabolism.

Figure 1 Percentage changes from baseline in (A) LDL-C, (B) non-HDL-C, (C) triglycerides, and (D) HDL-C across dose range for each statin in the VOYAGER database.

Copyright © 2010. The American Society for Biochemistry and Molecular Biology. Data reproduced from Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER database. J Lipid Res. 2010;51:1546–1553.²⁹

Note: Copyright © 2010. Elsevier. Data reproduced from Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol. 2010;105:69–76.⁵
Abbreviations: LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

Table 2 Effect of rosuvastatin (R) in the primary and secondary prevention of cardiovascular disease in randomized controlled trials

Clinical trial	Patients	Duration	Treatment groups	End point	Results
JUPITER^Citation52	17,802 apparently healthy individuals with normal levels of LDL-C and increased hsCRP	1.9 years (median)	R 20 mg vs placebo	Occurrence of first major cardiovascular events, including the combined incidence of nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, arterial revascularization procedures, and deaths due to cardiovascular causes	A 44% reduction in primary end point
CORONA^Citation58	5011 patients ≥ 60 years of age with New York Heart Association class II–IV ischemic, systolic heart failure	33 months (median)	R 10 mg vs placebo	The primary outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included death from any cause, any coronary event, death from cardiovascular causes, and the number of hospitalizations	No improvement in the primary outcome or the number of deaths from any cause, but reduced the number of cardiovascular hospitalizations
GISSI-HF^Citation59	4574 adult patients with chronic heart failure of New York Heart Association class II–IV, irrespective of cause and left ventricular ejection fraction	3.9 years (median)	R 10 mg vs placebo	Time to death, and time to death or admission to hospital for cardiovascular reasons	No effect on the clinical outcomes
AURORA^Citation65	2776 patients, 50–80 years of age, undergoing hemodialysis	3.8 years (median)	R 10 mg vs placebo	The primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events	No effect on the primary or the secondary end point

Abbreviations: LDL-C, low-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; vs, versus.

BarterPJBrandrup-WognsenGPalmerMKNichollsSJEffect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER databaseJ Lipid Res2010511546155319965573

 PubMed Web of Science ®Google Scholar

NichollsSJBrandrup-WognsenGPalmerMBarterPJMeta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER)Am J Cardiol2010105697620102893

 PubMed Web of Science ®Google Scholar

RidkerPMDanielsonEFonsecaFARosuvastatin to prevent vascular events in men and women with elevated C-reactive proteinN Engl J Med20083592195220718997196

 PubMed Web of Science ®Google Scholar

KjekshusJApetreiEBarriosVRosuvastatin in older patients with systolic heart failureN Engl J Med20073572248226117984166

 PubMed Web of Science ®Google Scholar

TavazziLMaggioniAPMarchioliREffect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trialLancet20083721231123918757089

 PubMed Web of Science ®Google Scholar

FellstromBCJardineAGSchmiederRERosuvastatin and cardiovascular events in patients undergoing hemodialysisN Engl J Med20093601395140719332456

 PubMed Web of Science ®Google Scholar