NSTE-ACS Patients With Inflammation Gain the Most Kidney Protection From Statin Pretreatment
In statin-naive patients with NSTE-ACS, high-dose rosuvastatin given on hospital admission prevents contrast-induced kidney damage and tends to improve clinical outcomes through 6 months, according to a study published in the December 2014 issue of JACC: Cardiovascular Interventions. Additionally, even greater protective effects were seen after statin therapy in patients with higher baseline inflammation.
This high-risk patient group requires aggressive medical management, including early, high-dose statin therapy, according to Anna Toso, MD, of Prato Hospital (Prato, Italy), and colleagues. “Statin benefits are evident independent of baseline [inflammation] in all risk categories, but this study shows that the higher the baseline [inflammation] levels, the higher the [acute kidney injury] and adverse event rates, and the higher the benefits of on-admission statin administration,” they write.
The investigators stratified 504 statin-naive ACS patients from the PRATO-ACS trial into tertiles based on baseline inflammation, as evidenced by high-sensitivity C-reactive protein (hs-CRP) levels (< 2.7 mg/L, ≥ 2.7 to < 7.5 mg/L, and ≥ 7.5 mg/L). All patients were scheduled for an early invasive strategy and, as part of the larger study, were randomly assigned to receive high-dose rosuvastatin (Crestor, AstraZeneca; 40 mg followed by 20 mg/day; n = 252) or no statin treatment (n = 252). After discharge, control patients received 40 mg/day atorvastatin.
Higher hs-CRP Tied to Greater Risk
Contrast-induced acute kidney injury (AKI; primary endpoint; defined as an increase in serum creatinine ≥ 0.5 mg/dL or 25% over the baseline value identified within 72 hours of contrast agent administration) was reported in 55 patients (10.9%). Those in the statin group (6.7%) were less likely than controls (15.1%) to develop AKI both before and after adjustment for baseline inflammation (adjusted OR 0.41; 95% CI 0.22-0.77; P = .005). The effect was confirmed using secondary AKI criteria.
Patients in the highest hs-CRP tertile were older and more likely to have diabetes and had lower ejection fraction and estimated creatinine clearance. “These higher hs-CRP values on admission signal higher risk of [contrast-induced] AKI and adverse clinical events,” Dr. Toso and colleagues write.
Overall, AKI rates progressively increased from the lowest to the highest hs-CRP tertile (P = .0001 for trend). But while control patients especially demonstrated an increase in AKI rates (P < .0001 for trend), the tertiles of statin-treated patients did not show differences (P = .65 for trend). This pattern was maintained in the third tertile of controls after adjustment for baseline hs-CRP values (P = .002 vs first and second tertiles).
Cumulative rates of adverse cardiovascular and renal events at 30 days were higher overall in the third hs-CRP tertile (P < .0001 for trend). However, within the group with the most inflammation, statin-treated patients had a lower rate of events compared with controls (7.2% vs 17.4%; P = .043). Results at 6 months showed this pattern continuing—though without statistical significance—with less death and MI in statin-treated patients (6.02% vs 13.04%; P = .12).
Throwing Support Behind Early, High-Dose Statins
The study “confirms the relationship between baseline hs-CRP levels and [contrast-induced] AKI development even in NSTE-ACS patients subjected to [an] early invasive strategy and shows a close link between baseline hs-CRP levels and prognosis,” Dr. Toso and colleagues write. “[Baseline inflammation] helps identify patients with particularly high clinical risk—those very patients who presented phenotypes associated with higher risk of [AKI] development.”
Moreover, the results substantially support statin pretreatment in patients with very high baseline inflammation, they add. “Even short-term statin treatment may reduce susceptibility to [contrast-induced] AKI given its anti-inflammatory effects, both systemic and on the kidneys in particular.”
With regard to clinical events, the authors note that “patients with higher markers of inflammation are more subject to adverse events, and it is these very patients who benefit most from statin pretreatment.”
It remains unknown whether the protection is related to the “anti-inflammatory properties of rosuvastatin,” Dr. Toso and colleagues say, but “our findings represent a further reason in favor of early use of high-dose statin therapy and assessment of hs-CRP in ACS patients.”
Toso A, Leoncini M, Maioli M, et al. Relationship between inflammation and benefits of early high-dose rosuvastatin on contrast-induced nephropathy in patients with acute coronary syndrome: the pathophysiological link in the PRATO-ACS study (Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention). J Am Coll Cardiol Intv. 2014;7:1421-1429.
- The study was supported by the Centro Cardiopatici Toscani.
- Dr. Toso reports no relevant conflicts of interest.