Is There a Role for Hypolipidaemic Drug Therapy in the Prevention or Treatment of Microvascular Complications of Diabetes?

A plethora of statin survival trials and meta-analyses have demonstrated a substantial reduction in cardiovascular disease (CVD) morbidity and mortality, mainly related to a low-density lipoprotein cholesterol (LDL-C) reduction [1]. One of them, the prospective, randomised, double-blind, secondary prevention Treating to New Targets (TNT, n = 10,001) trial, randomised patients to either 10 or 80 mg/day of atorvastatin. During a 5-year period the 10 mg/day patients had a rate of major CVD events of 10.9%, while those randomised to 80 mg/day had an 8.7% event rate. This was despite the concurrent and successful treatment of other CVD risk factors, the 22% (p<0.001) CVD risk reduction compared with atorvastatin 10 mg/day, and the achievement of LDL-C levels of 77 mg/dl (well below those suggested by guidelines at that time) [2]. Similar were the data from the prespecified post hoc subgroup analysis of TNT that included patients (n = 1,401) with type 2 diabetes mellitus (T2DM) that had mild to moderate chronic kidney disease (CKD, a microvascular complication of DM) or normal renal function [3]. Compared with 10 mg of atorvastatin, 80 mg of atorvastatin reduced the relative risk (RR) of major CVD events by 35% (absolute event rate 21 vs 14%; hazard ratio (HR) = 0.65; 95% confidence interval (CI) = 0.43-0.98; p = 0.04) in those with CKD and by 10% in patients with T2DM and normal renal function (14.8 vs 14%; HR = 0.90; p = 0.56) [3]. In any case (with or without diabetic nephropathy) a residual CVD risk was present, as in all statin survival trials [1]. In the Steno-2 study, intensive multifactorial intervention in patients with T2DM during a 5-year follow-up, significantly reduced CVD events (HR = 0.47, 95% CI = 0.24-0.73, p = 0.008) and CVD mortality (HR = 0.43, 95% CI = 0.19-0.94, p = 0.04), but