Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

Abstract

Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD.

Do outpatient statins and ACEIs/ARBs have synergistic effects in reducing the risk of pneumonia? A population-based case-control study

“…Some studies suggested that the combination of ACEIs/ARBs and statins may have synergic effects and produce better outcomes than their sole use in particular circumstances. For example, one study suggested that concomitant ACEI and statin use appeared to beneficially modulate changes in the glomerular filtration rate in men with stable coronary artery disease [ 3 ]. It was reported that a combination of and early treatment with statins and ACEIs/ARBs could prevent extensive inflammatory responses in patients undergoing coronary artery bypass surgery [ 4 ].…”

Advances in Chronic Kidney Disease

“…Using a combination of in vitro and in vivo approaches, it is shown that metformin may be protective against renal fibrosis via inhibition of ERK signaling [ 29 ]. The use of angiotensin-converting enzyme inhibitors (ACEI) with atorvastatin may be renoprotective in male patients with coronary artery disease, assessed by GFR [ 30 ]. Finally, the role of mTOR inhibitors as therapeutic agents for the treatment of non-clear cell renal cell carcinoma, diabetic nephropathy and renal transplantation, with emphasis on the mechanistic findings underlying the renoprotective effects, is reviewed [ 31 ].…”