AT KIDNEY WEEK 2014
PHILADELPHIA (FRONTLINE MEDICAL NEWS)– Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.
The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA ( JAMA 2015; doi:10.1001/jama.2014.15284 ).
Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.
In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”
The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2 (POISE-2)trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.
The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.
At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m2.
Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.
Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.
AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients – a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.
Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients – another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.
A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).
Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.
“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.
Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).
Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.