JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) marked an important juncture in. BNP in 11, participants without cardiovascular disease in the JUPITER Un Estudio Intervencionista que Evalúa Rosuvastatina (JUPITER, Justification. Desde que en el estudio JUPITER 34 se detectó una mayor incidencia de DM en el grupo con rosuvastatina 35, varios metaanálisis han.
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Rosuvastatin is a new generation Jupitee reductase inhibitor which exhibits some unique pharmacologic and pharmacokinetic properties. It has low extrahepatic tissue penetration, low potential for CYP3A4 interactions and substantial LDL-C lowering capacity and therefore has distinct advantages.
We conducted a Medline literature search to identify rosuvastatin papers published in English. In this review, we outline the pharmacology of rosuvastatin, highlighting its efficacy and safety. We also review the major clinical trials with reference to primary and secondary prevention, familial hypercholesterolaemia and comparison with other statins.
Finally we address its place in clinical practice. Esrudio heart disease IHD is the leading cause of mortality worldwide and constitutes a major health burden.
In the United Kingdom, data from the Health Surveys for England suggest that while mortality may be declining, cardiovascular disease morbidity continues to rise. Epidemiological studies have established a strong correlation between cholesterol and the incidence rosuvastatima cardiovascular disease. The associated morbidity and mortality is positively correlated to low density lipoprotein cholesterol LDL-C and inversely related to high density lipoprotein cholesterol HDL-C.
Early detection and treatment with statins has been shown to reduce morbidity and mortality in those with heterozygous familial hypercholesterolaemia. The reduction in cardiovascular events from statin therapy is proportional to the LDL-C rosuvastatnia.
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
The drive towards more stringent goals for LDL-C lowering in cardiovascular risk prevention has brought high impact statin therapy into focus. These affect their extrahepatic tissue penetration and drug interactions with potential safety implications. Rosuvastatin which is a new generation HMG-CoA reductase inhibitor exhibits some unique pharmacologic and pharmacokinetics properties.
Its potential impact in primary and secondary prevention of cardiovascular disease in different groups including heart failure, elderly, renal failure and diabetes, and also in combination with other lipid lowering drugs is the subject of ongoing clinical studies.
In this review, we will outline the pharmacology of rosuvastatin; highlight its efficacy and safety. We will also review clinical studies with reference to primary and secondary prevention, familial hypercholesterolaemia and comparison with other statins. Finally we will address its place in clinical practice. Other HMG-CoA reductase inhibitors are either natural, mevinic acid derived lovastatin, simvastatin, pravastatin or synthetic, heptenoic acid derived atorvastatin, fluvastatin.
Rosuvastatin belongs to a new generation of methane- sulphonamide pyrimidine and N -methane sulfonyl pyrrole-substituted 3, 5- dihydroxy-heptenoates. Although the characteristic statin pharmacophore remains similar to other statins, the addition of a stable polar methane-sulphonamide group provides low lipophilicity and enhanced ionic interaction with HMG-CoA reductase enzyme thus improving its binding affinity to this enzyme.
This enzyme converts HMG-CoA to mevalonic acid in the cholesterol biosynthetic pathway which is the rate limiting step in cholesterol synthesis. Rosuvastatin therefore decreases hepatic sterol synthesis, which, in turn, leads to a decreased concentration of hepatocellular cholesterol. Hepatocytes respond to this decreased intracellular cholesterol concentration by increased synthesis of LDL receptors to enhance hepatic LDL reuptake from the circulation. The net result of this process is an increased fractional catabolism of LDL which reduces serum LDL-C concentration and total cholesterol.
This may be secondary to marked inhibition of cholesterol synthesis which decreases LDL production. Rosuvastatin has demonstrated comparable reductions in triglyceride TG concentrations to other statins with the greatest benefit seen in patients rosuvastatiba high baseline TG levels.
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
The affinity of rosuvastatin for the active site of the enzyme is four times greater than the affinity of HMG-CoA for the enzyme. This high affinity coupled with tight ionic interaction result in a slow recovery of enzyme activity after removal of rosuvastatin.
Its affinity for OATP-1B1 is comparable to atorvastatin but significantly greater than pravastatin or simvastatin. Rosuvastatin is therefore primarily distributed to hepatocytes while peripheral concentrations are low. As observed with other statins, rosuvastatin has pleiotropic effects independent of HMG-CoA reductase inhibition. These include improvements in endothelial function, anti-inflammatory, antithrombotic and anti-oxidant effects.
This in turn reduces endothelial dysfunction that has been implicated in atherosclerosis. Rosuvastatin reduces high sensitivity C reactive protein hsCRP which is a marker of inflammation and an independent cardiovascular risk predictor and other inflammatory markers.
After a single oral dose the peak plasma concentration is reached at 5 hours. This is longer than estuddio HMG-CoA inhibitors which achieve maximum plasma concentrations in less than 3 hours.
In compiled data from pharmacokinetic trials, the peak plasma concentration and area under the concentration time curve show a largely linear relationship as the dose of rosuvastatin increases from 5 to 80 mg. This does not reduce the cholesterol lowering potency; therefore rosuvastatin can be taken with or without food, and in the morning or evening.
The mean volume of distribution is litres in steady state. Rosuvastatin is less lipophilic than other statins such as atorvastatin and simvastatin but more lipophilic than pravastatin. Penetration of statins into extra-hepatic tissues occurs jupitre passive diffusion and is dependent on their lipophilicity. This has implications on their muscle safety as increased rhabdomyolysis was reported in patients on lipophilic agents like cerivastatin and lovastatin.
Rosuvastatin is less likely to cause metabolic drug to drug interactions since it has limited metabolism by CYP isoenzymes. Their plasma concentrations are increased by inhibitors of CYP3A4 such as itraconazole, protease inhibitors and macrolide antibiotics. Data from Soran et al. Rosuvastatin has a plasma half life of 19 hours which is longer than atorvastatin 15 hours rsuvastatina simvastatin 2—3 hours.
There have been a number of clinical studies evaluating rosuvastatin on its own, against placebo and against other statins in various clinical settings.
Clinical studies have demonstrated the benefits of statins in primary prevention. The participants had a mean Framingham risk score at baseline of The observed increase in HDL-C was transient. Results showed that rosuvastatin was associated with a significant reduction in first major cardiovascular events HR 0.
Previously, there has been limited data on statin benefits in women, black and Hispanic patients. Another series of sub analyses have looked at etsudio profiles and hsCRP particularly in relation to residual cardiovascular risk.
In all estudjo them, participants who achieved low concentrations of hsCRP in addition to low values of the lipid parameters of interest had the best outcome. When hsCRP gosuvastatina included in enrolment of primary prevention, rosuvastatin produced greater benefit when compared with other statins. These results compare favourably with other primary prevention trials using different statins.
The beneficial effects of statin therapy in patients with ischaemic heart orsuvastatina are well known. The 4S study showed that simvastatin 20 mg to 40 mg daily significantly reduced major coronary events, coronary death and overall mortality in patients post-MI or those with ischaemic heart disease. There were significant reductions in non fatal acute myocardial infarction and in other secondary composite endpoints, with no difference in cardiovascular or all-cause mortality.
Statistical significance was not demonstrated for the prespecified primary clinical outcome which was time to first occurrence of major coronary event. Several studies have suggested that reduction in plaque volume is linked to the clinical outcome. A median reduction of 6.
Rosuvastatin: A Review of the Pharmacology and Clinical Effectiveness in Cardiovascular Disease
It must be noted that the study was non-comparative and open label. The lack of plaque regression may have occurred because low risk patients with minimal subclinical carotid atherosclerosis were used in the study.
Effect of Rosuvastatin versus Rosuastatina study compared maximal doses of rosuvastatin and atorvastatin on coronary atheroma. ApoA-1 ratio at 3 months when compared with atorvastatin 80 mg. Previous studies have identified ApoB: ApoA-1 ratio as an important predictor of myocardial rosuastatina. In the same study rosuvastatin 20 mg achieved similar LDL-C reduction as atorvastatin 80 mg.
This study therefore showed that rosuvastatin 20 mg is as effective as atorvastatin 80 mg in intensive statin therapy. A crucial observation of this study was that in both treatment arms, most patients did not achieve these targets, highlighting the rosuvastatinw of intensive statin therapy to meet these goals.
The superior lipid lowering effect of rosuvastatin makes it a good candidate for intensive lipid lowering. Previous primary prevention trials have poorly demonstrated reduction in coronary events in women.
Randomised control trial RCT data roskvastatina limited regarding statin efficacy in the elderly.
Rosuvastatina y el estudio JUPITER by Ybel Fermin on Prezi
There were no serious safety concerns raised for this age group compared with younger subjects. Advanced kidney disease is associated with high cardiovascular morbidity and death. RCT evidence has shown an inconsistent relationship between cardiovascular outcome and LDL-C in haemodialysis patients.
An Assessment of Survival and Cardiovascular Events investigated the effects of rosuvastatin on cardiovascular risk in haemodialysis patients. It was a randomised, double blind, placebo-matched, multicentre trial involving patients aged 60—80 years. Good median reductions were achieved in LDL-C Despite these reductions, there was no significant effect of treatment on the composite primary end point time to a major cardiovascular event or its individual components nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.
Thus, no relationship was demonstrated between cardiovascular end points and either baseline rosuvastagina follow up LDL-C.
A further evaluation of secondary outcomes showed no reduction in all-cause mortality or non-cardiovascular death. Type 2 diabetes is associated with increased risk of coronary heart disease. Hupiter, the LDL-C of diabetic patients predicted their risk of stroke.
Sub-group analyses of 4S showed the benefits of simvastatin in reducing major coronary events and revascularisation in diabetic patients with coronary heart disease.
However, the reduction in total and cardiovascular mortality was not significant due to the small sample size. A randomised double blind double-dummy, multicentre, phase IIIb, parallel-group study to compare the efficacy and safety of rosuvastatin 10 mg and 20 mgand atorvastatin 10 mg and 20 mg in patients with type 2 diabetes mellitus ANDROMEDA showed that rosuvastatin produced greater reductions in LDL-C, ApoB and jupitre cholesterol when compared with equal doses of atorvastatin.
A greater proportion of patients on rosuvastatin achieved European LDL-C goals compared to those on atorvastatin. Studies comparing different lipid lowering regimens demonstrate that only high impact therapy with rosuvastatin 40 mg or atorvastatin 80 mg achieves this goal when administered estufio monotherapy.
The use of LDL apheresis in heterozygous FH patients is thus unclear and at present maximal drug therapy is the preferred treatment. The use of rosuvastatin did however reduce hospitalisation from cardiovascular causes. Studies estudi children with heterozygous FH have shown the safety and efficacy of statins, including their effect on carotid intima thickness and arterial flow mediated dilation. The effects on other lipid parameters and safety were consistent with other estuxio studies in adults and children.
These benefits were present in all patient groups including women, non smokers and other low risk patients. The SPARCL study showed that intensive statin therapy with rosuvasratina 80 mg daily resulted in significant reduction in recurrent stroke.
Intensive therapy with rosuvastatin may yield similar benefits.