Risk of Kidney Injury Not Affected by High-Potency Statin Regimen in ACS Patients

DALLAS, TX—A high-dose statin regimen does not raise serum creatinine or the risk of kidney injury in patients with acute coronary syndromes (ACS), according to results of a pooled analysis presented November 19, 2013, at the annual American Heart Association Scientific Sessions.

Researchers led by Amy A. Sarma, MD, of Brigham and Women’s Hospital (Boston, MA), examined the populations of 2 large trials that randomized ACS patients to high- and moderate-potency statin regimens. PROVE IT-TIMI (Cannon et al; N Engl J Med. 2004) assigned 4,162 patients to either pravastatin 40 mg or atorvastatin 80 mg while A-to-Z (de Lemos et al. JAMA. 2004) randomized 4,497 to placebo for 4 months followed by simvastatin 20 mg or simvastatin 40 mg for 1 month followed by simvastatin 80 mg. Kidney injury was defined by the KDIGO classifications with serum creatinine as the referent, and patients were followed for 2 years in both studies.

High-Potency Statins Safe

Serum creatinine increased from baseline to month 1 and then steadily decreased thereafter in both trials. Moreover, in PROVE IT-TIMI 22, there was a consistent trend toward improved serum creatinine in patients randomized to the high-potency regimen.

Looking at the incidence of long-term serum creatinine increase in both trials, the researchers found no differences between a moderate- or high-potency regimen (table 1).

Table 1. Incidence of Kidney Injury: Moderate vs. High Statin Regimen

In the first 4 months of the A-to-Z trial, while the moderate-regimen group was on placebo, there were no differences between the study groups with respect to a 1.5-fold (P = 0.51) or twofold (P = 0.18) increase in serum creatinine.

There were also no differences in kidney injury looking specifically at the subgroup of patients in both trials who had baseline eGFR < 60 ml/min/1.73m².

Lastly, there were no differences in kidney injury-related adverse events between a moderate- or high-potency regimen within the first 4 months (OR 1.15; 95% CI 0.61-2.16; P = 0.67) or long-term (OR 1.06; 95% CI 0.68-1.67; P = 0.78) when the populations of both trials were combined.

“Considering the recently updated lipid guidelines, these findings provide important reassurance that a high-potency statin regimen will not increase the incidence of adverse renal events,” Dr. Sarma said.

Caution Warranted in Individual Patients

Discussing the study, Tara I. Chang, MD, MS, of Stanford University (Stanford, CA), commented that both studies included in the analysis were made up of younger, less often female patients with a lower incidence of diabetes than a general MI population. “Age, sex, and diabetes are strong risk factors of more subsequent kidney injury,” she said, adding that chronic kidney disease is the “most important” risk factor of AKI and the percentage of patients with that complication was substantially lower than a general MI population in PROVE IT-TIMI 22.

Another point to consider, Dr. Chang explained, is the ability to detect a safety signal. Compared with 2 more recent large observational studies that found significant safety levels, the current analysis results in similar outcomes regardless of the wide confidence intervals.

Lastly, she said, the “definition of high-potency varies,” thus outcomes are bound to differ based on the exact regimen used.

“I don’t necessarily disagree with Dr. Sarma’s conclusions that for most people after ACS, high-potency statins would be warranted,” Dr. Chang concluded. “I think we just need to be cautious about the individual patient when we consider the risks and benefits.”

Study Details

Baseline characteristics were well balanced between treatment arms in both studies. A greater proportion of patients enrolled in A-to-Z had diabetes, which may have contributed to the higher levels of serum creatinine and lower eGFR compared with patients enrolled in PROVE IT-TIMI 22.

Sarma A. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome. Presented at: American Heart Association Scientific Sessions; November 20, 2013; Dallas, TX.

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