ORIGINAL ARTICLE

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

V G Athyros¹, D P Mikhailidis³, A A Papageorgiou², A N Symeonidis⁴, A N Pehlivanidis¹, V I Bouloukos¹ and M Elisaf⁵

¹ Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, 49 Konstantinoupoleos St, Thessaloniki, 546 42, Greece
² Second Propedeutic Department of Internal Medicine, Aristotelian University
³ Department of Clinical Biochemistry, Royal Free Hospital, Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK
⁴ Greek Society of General Practitioners, 21 N. Koudourioti St, Thessaloniki, 546 25, Greece
⁵ Department of Internal Medicine, Medical School, University of Ioannina, 451 10, Greece

Correspondence to:
Correspondence to:
Dr V G Athyros
15 Marmara St, Thessaloniki, 551 32, Greece; athyros{at}med.auth.gr

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 µmol/litre (13 mg/litre). The on study creatinine clearance (CrCl), as estimated (for up to 48 months) by the Cockroft-Gault 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.

Abbreviations: ACE, angiotensin converting enzyme; C, cholesterol; CHD, coronary heart disease; CI, confidence interval; CrCl, creatinine clearance; GFR, glomerular filtration rate; GREACE, Greek atorvastatin and coronary heart disease evaluation; HDL, high density lipoprotein; HPS, heart protection study; HR, hazard ratio; K/DOQI, kidney disease outcomes and quality initiative; LDL, low density lipoprotein; NCEP, national cholesterol educational programme; SCr, serum creatinine; TG, triglyceride

Keywords: renal function; dyslipidaemia; statins; coronary heart disease

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