The Incidence of Kidney Injury for Patients Treated With a High‐Potency Versus Moderate‐Potency Statin Regimen After an Acute Coronary Syndrome

Abstract

BackgroundObservational studies have raised concerns that high‐potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy.Methods and ResultsPROVE IT‐TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A‐to‐Z enrolled 4497 subjects after ACS and randomized them to a high‐potency (simvastatin 40 mg/day×1 months, then simvastatin 80 mg/day) versus a delayed moderate‐potency statin strategy (placebo×4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow‐up. In A‐to‐Z, the incidence of a 1.5‐fold or ≥0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high‐potency statin regimen versus 12.4% for those on a delayed moderate‐potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT‐TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury‐related adverse events (AEs) was not statistically different for patients on a high‐potency versus moderate‐potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78).ConclusionsFor patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high‐potency statin regimen did not increase the risk of kidney injury.

Statin use and the risk of acute kidney injury in older adults

“…In contrast, previous RCTs have not found a significant association between statin treatment and the risk of AKI, or an excess risk of AKI for high potency vs moderate/low potency regimens [19–21]. A recent RCT examined the risk of AKI associated with a short course of atorvastatin 40–80 mg daily during the perioperative period among adult patients receiving cardiac surgery, and found no significant effect overall (HR associated with atorvastatin 1.06 (95% CI 0.78, 1.46)) or among those who were naïve to statin treatment at baseline (HR 1.61, 95% CI 0.86, 3.81)) [22].…”

Statins in Type 2 Diabetes

“…Similarly, the use of a high-potency statin regimen did not increase the risk of kidney injury was observed in 2 large randomized trials of statin therapy in patients with acute coronary syndrome; PROVE IT-TIMI 22 [50,55] (atorvastatin 80 mg/day) including 4,162 patients, and A-to-Z trial (pravastatin 40 mg/day for 1 month + simvastatin 80 mg/day after 1 month) including 4, 497 patients. [72] As mentioned in the previous section, the ATTEMP (Assessing the treatment Effect in Metabolic syndrome without Perceptible diabetes) study [67] showed that multifactorial intervention in patients with metabolic syndrome without established CVD improved renal function and reduced serum uric acid levels. Of importance, these changes were more prominent in stage 3 chronic kidney diseases patients.…”

Statins can improve proteinuria and glomerular filtration rate loss in chronic kidney disease patients, further reducing cardiovascular risk. Fact or fiction?

“…Moreover, two prospective, randomized, controlled trials, the TNT trial (n = 10,001), in patients with stable CHD, and the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial, in patients with acute coronary syndromes (ACS), used the 80 mg/day dose of atorvastatin with beneficial or, in the worst case, neutral effect on renal function; no case of acute renal failure was reported [63,64,82,83]. Besides, the joint analysis of IDEAL, TNT, CARDS, ASPEN, SPARCL, and other statin survival placebo-controlled trials, using high-potency statins, mainly atorvastatin at 80 mg/ day, did not show adverse events related to renal function and especially AKI after 149,882 patient-years of follow-up with high potency statins compared with lower potency statins or placebo [84].…”