The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study

Abstract

Background: Little is known about statins in the prevention of dyslipidaemia induced renal function decline. The secondary coronary heart disease (CHD) prevention GREACE study suggested that dose titration with atorvastatin (10-80 mg/day, mean dose 24 mg/day) achieves the national cholesterol educational programme treatment goals and significantly reduces morbidity and mortality, compared with usual care. Aims: To report the effect of statin on renal function compared with untreated dyslipidaemia in both treatment groups. Methods/Results: All patients had plasma creatinine values within the reference range , 115 mmol/litre (13 mg/litre). The on study creatinine clearance (CrCl), as estimated (for up to 48 months) by the CockroftGault formula, was compared within and between treatment groups using analysis of variance to assess differences over time. Patients from both groups not treated with statins (704) showed a 5.2% decrease in CrCl (p , 0.0001). Usual care patients on various statins (97) had a 4.9% increase in CrCl (p = 0.003). Structured care patients on atorvastatin (783) had a 12% increase in CrCl (p , 0.0001). This effect was more prominent in the lower two quartiles of baseline CrCl and with higher atorvastatin doses. After adjustment for 25 predictors of all CHD related events, multivariate analysis revealed a hazards ratio of 0.84 (confidence interval 0.73 to 0.95; p = 0.003) with every 5% increase in CrCl. Conclusions: In untreated dyslipidaemic patients with CHD and normal renal function at baseline, CrCl declines over a period of three years. Statin treatment prevents this decline and significantly improves renal function, potentially offsetting an additional factor associated with CHD risk.

Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease

“…[6][7][8][9] Only patients with established CHD were included: history of prior myocardial infarction or 470% stenosis of at least one coronary artery, as documented by a coronary angiogram. Patients with recent acute coronary syndromes were not excluded.…”

“…We report on-study treatment in Table 3 according to this information. There were no significant differences between the four treatment groups in demographic characteristics and CHD factors at baseline (Table 1), in baseline lipid values and renal function (Table 2), in concomitant drug treatment during the study (Table 3), and level of glycemic control [6][7][8][9] or in blood pressure during the study (Table 2). Both at entry and during the study, smokers were similarly distributed in the four treatment groups.…”

“…Both at entry and during the study, smokers were similarly distributed in the four treatment groups. [6][7][8][9] All patients in the four treatment groups received advice on life-style changes and the body mass index (an approximate index of compliance) at baseline and during the study was similar in all groups. Thus, the beneficial effect on clinical outcomes should mainly be attributed to statin or ACEI treatment or both.…”

“…The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study [6][7][8][9] was a prospective, randomised, target based, open-label and intention-to-treat secondary CHD prevention trial. GREACE showed that the structured management of dyslipidaemia with dose titration of atorvastatin can achieve the National Cholesterol Educational Program (NCEP) low-density lipoprotein cholesterol (LDL-C) treatment goal (o2.6 mmol/l;100 mg/dl).…”

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

“…Consistent with this view, increasing evidence suggests that statins are also associated with a reduced risk of hepatocellular carcinoma 128 . On the other hand, post-hoc analyses of randomized clinical trials have shown that atorvastatin may be nephroprotective 129,130 . To date, however, there are no large randomized clinical trials testing the long-term effects of statins on histological liver endpoints in patients with NAFLD.…”