Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury: A Randomized Clinical Trial | Journal Scan
Does aspirin compared with placebo, and clonidine compared with placebo, alter the risk of perioperative acute kidney injury?
This was a prespecified substudy of POISE-2 (Perioperative Ischemic Evaluation 2), a randomized trial that used a 2 x 2 factorial design to allow separate evaluation of low-dose aspirin versus placebo and low-dose clonidine versus placebo in 10,010 patients undergoing noncardiac surgery. Participants were randomly assigned in a 1:1:1:1 ratio to receive clonidine and aspirin, clonidine and aspirin placebo, clonidine placebo and aspirin, or clonidine placebo and aspirin placebo. In POISE-2, neither aspirin nor clonidine administered perioperatively reduced the risk of composite of 30-day mortality or nonfatal myocardial infarction. Participating in this substudy were 88 of 135 POISE-2 sites. The primary outcome of the substudy was acute kidney injury (a sudden loss of kidney function defined by an acute increase in serum creatinine concentration of ≥50% or an acute increase of ≥0.3 mg/dl).
The analytic sample in the substudy included 6,905 patients. Compared to placebo, aspirin did not alter the risk of acute kidney injury (13.4% of patients in aspirin group vs. 12.3% of patients in placebo group; adjusted risk ratio [RR], 1.10; 95% confidence interval [CI], 0.96-1.25). Compared to placebo, clonidine did not alter the risk of acute kidney injury (13.0% of patients in clonidine group vs. 12.7% of patients in placebo group; adjusted RR, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of bleeding, and the development of such bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs. 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Clonidine increased the risk of hypotension, and the development of such clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs. 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58).
The authors concluded that neither aspirin nor clonidine administered perioperatively reduces the risk of acute kidney injury.
This is an important substudy of the POISE-2 trial, which established that neither aspirin nor clonidine, when given perioperatively, reduced the risk of 30-day mortality or nonfatal myocardial infarction. The findings from the substudy give further support to a perioperative strategy that does not include either of these therapies. And there may be harm. Mediated through hypotension, clonidine may actually heighten the risk of acute kidney injury; mediated through increased bleeding, aspirin too may contribute to acute kidney injury. On balance, initiation of therapy with aspirin or clonidine is probably best avoided in the perioperative period.
Keywords: Acute Kidney Injury, Aspirin, Clonidine, Creatinine, Hemorrhage, Hypotension, Perioperative Period, Risk
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