Perioperative Rosuvastatin Fails to Curb Cardiac-Surgery Complications, Tied to Renal Injuries

Patrice Wendling

May 04, 2016

BEIJING, CHINA — Perioperative rosuvastatin did not prevent atrial fibrillation (AF) or myocardial injury after elective cardiac surgery and was associated with significantly more acute kidney injury (AKI) than placebo in the Statin Therapy in Cardiac Surgery (STICS) trial[1].

"Given the lack of good evidence of beneficial effects of perioperative statin therapy in our trial, the adverse effects on renal function warrant careful consideration," according to the investigators, led by Dr Zhe Zheng (Chinese Academy of Medical Sciences and Peking Union College, Beijing).

AKI occurred 48 hours after surgery in 24.7% of patients randomized to rosuvastatin and 19.3% given placebo (P=0.005). This was driven largely by stage 1 AKI (21% vs 17.5%; P=0.047), but there was also significant stage 2 or 3 AKI (absolute excess 1.8 percentage points; P=0.02).

Plasma creatinine levels were also significantly higher with rosuvastatin than placebo 48 hours after surgery and maintained up to 5 days.

Although the adverse effects on renal function may relate to patient ethnicity or use of rosuvastatin, which has been shown in other settings to increase proteinuria, but not creatinine levels or kidney injury, "a class effect of statin therapy in patients undergoing cardiac surgery cannot be ruled out," they write in the May 5, 2016 issue of the New England Journal of Medicine.

As recently reported by heartwire from Medscape, a randomized trial examining statins as neuroprotective agents showed that atorvastatin failed to reduce AKI in patients undergoing cardiac surgery and increased the risk of AKI when initiated in statin-naive patients with preexisting chronic kidney disease.

Lack of Beneficial Effects

Of the 1922 patients in STICS, 653 were taking a statin at randomization. Statin therapy was stopped before patients were randomly assigned to receive rosuvastatin 20 mg once daily or placebo for up to 8 days before surgery and for 5 days thereafter. Most patients underwent CABG surgery (87%), 10% aortic-valve replacement alone, and 1% some other type of surgery. Among the 1874 patients randomly assigned patients who underwent surgery, treatment adherence was 92% in each group.

Concentrations of LDL cholesterol and high-sensitivity C-reactive protein after surgery were lower in patients assigned to rosuvastatin than to placebo (P<0.001).

The rosuvastatin and placebo groups, however, had a similar incidence of postoperative AF (21% vs 20%; odds ratio 1.04; P=0.72) and the co–primary outcome of myocardial injury within 120 hours after surgery, as assessed by the cumulative release of cardiac troponin 1 (between-group difference 1%; P=0.80).

The investigators point out that practice guidelines currently recommend perioperative statin therapy for the prevention of AF and other in-hospital complications after cardiac surgery. An updated meta-analysis of prior randomized trials showed an approximate halving of the incidence of postoperative AF with statins vs placebo, but those trials had small patient numbers and only four trials prespecified postoperative AF as an outcome. A recent systematic Cochrane review of the trials also reported evidence of selective reporting and publication bias.

STICS involved more patients, particularly more AF cases, than in all the previous trials combined, the investigators note, but they acknowledge that a potential limitation of the study is that the average duration of treatment was shorter than was planned in most previous trials. Still, even among the 449 patients who started rosuvastatin 4 to 8 days before surgery, there was no significant between-group difference in the incidence of AF or myocardial injury.

Further, there was no beneficial effect of starting statin therapy on either outcome among the 1269 statin-naive patients in the trial. Among the 653 patients who were taking statin therapy at the time of randomization, "the finding that there was no benefit from continuing statin therapy vs stopping it before surgery is directly relevant to current practice and indicates that continuing statin therapy during the perioperative period does not prevent in-hospital postoperative complications," they write.

The study was supported by the British Heart Foundation, European Network for Translational Research in Atrial Fibrillation of the European Commission Seventh Framework Program, the Oxford Biomedical Research Centre, and the UK Medical Research Council, with a small unrestricted grant from AstraZeneca. Dr Zheng reported no relevant financial relationships. Disclosures for the coauthors are listed on the journal website.

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