DALLAS – High-potency statin therapy given post acute coronary syndrome did not raise serum creatinine or cause more risk of acute kidney injury than low-potency statin regimens did in a new analysis of two published landmark randomized clinical trials.
"Considering the recently updated AHA/American College of Cardiology lipid guidelines, which call for the use of high-potency statins in millions more patients, these findings provide important reassurance that a high-potency statin regimen will not increase the incidence of adverse renal events," Dr. Amy Sarma said in presenting the study results at the American Heart Association scientific sessions.
Dr. Amy Sarma
She noted that a recent Canadian observational study utilizing Canadian and U.S. administrative databases totaling more than 2 million patients over age 40 who were newly placed on statin therapy showed an adjusted 1.34-fold increased rate of hospitalization for acute kidney injury within the first 120 days in those on a high- as compared to a low-potency regimen, and a 1.11-fold increased risk beyond 120 days through the end of the first year (BMJ 2013;346:f880). Both risk elevations were statistically significant.
However, observational studies such as this are prone to bias in the form of potentially crucial differences between the patients given a prescription for statins and those who aren’t. For this reason, Dr. Sarma and her coinvestigators turned for guidance to two randomized trials of high- versus low-dose statins, since this study design obviates the risks of confounding. The trials were PROVE IT-TIMI 22 (N. Engl. J. Med. 2004;350:1495-504) and the A-to-Z trial (JAMA 2004;292:1307-16).
PROVE IT included 4,122 patients randomized within 10 days post ACS to standard background therapy plus either pravastatin at 40 mg/day or atorvastatin at 80 mg/day. A-to-Z involved 4,497 patients who were placed on simvastatin at either 20 or 80 mg/day within 5 days post ACS. Both trials had a median follow-up of 2 years, and both featured serial measurements of serum creatinine. Two-thirds of subjects in PROVE IT had a baseline estimated glomerular filtration rate below 90 mL/min per 1.73 m2, while two-thirds of those in A-to-Z had a baseline eGFR less than 60, noted Dr. Sarma of Brigham and Women’s Hospital, Boston.
In both studies, mean serum creatinine rose equally during the first 30 days of statin therapy, regardless of treatment potency, and then levels declined. In PROVE IT, for example, serum creatinine in the pravastatin and atorvastatin arms rose by 0.96% and 0.97% above baseline, respectively, at 30 days. Values then dropped by 2.88% and 3.85% from baseline at 4 months, and by 3.88% and 5.83% at 16 months.
In both studies, there was no difference between the high- and low-potency statin groups in the incidence of any increase in serum creatinine of at least 1.5-fold, 2.0-fold, or 3.0-fold greater than baseline. In other words, there was no hint of a safety signal, she added.
Dr. Sarma reported having no financial conflicts of interest.