Low-Dose Aspirin Better Than High- For Stoke Prevention After Surgery - ACE

Low-dose aspirin taken before and after carotid endarterectomy surgery is more effective than higher doses of the nonsteroidal anti-inflammatory in preventing stroke, myocardial infarction and death, researchers report in the June 26 issue of The Lancet.

Data from the Aspirin and Carotid Endarterectomy (ACE) trial, a randomized, double-blind, controlled clinical study involving 2,849 patients slated for endarterectomy, find 81 mg and 325 mg daily doses of aspirin (acetylsalicylic acid) taken prior to surgery and for three months afterward are more effective in lowering the risk of stroke, MI and mortality than 650 mg and 1,300 mg doses of the drug.

Conducted by D. Wayne Taylor, MA, McMaster University (Hamilton, Ontario) et al., the trial was initiated on the heels of the North American Symptomatic Carotid Endarterectomy Trial, published in 1991 in the New England Journal of Medicine.

Unlike the new ACE findings, NASCET investigators observed in a secondary analysis a lower risk of perioperative stroke and death among patients who took higher aspirin levels (650 mg-1,300 mg) before surgery. The ACE study was designed to determine "whether perioperative complication rates are affected by dose of acetylsalicylic acid," Taylor et al. note.

The trial was conducted in 74 medical centers, the majority in the U.S. (48) and Canada (19), as well as four in Australia and one each in Italy, Argentina and Finland. Most of the centers were NASCET sites. The National Institute of Neurological Disorders & Stroke funded the study.

Eligibility requirements included pending endarterectomy for arteriosclerotic disease and the ability to tolerate 1,300 mg of aspirin daily. Exclusion criteria included participation in another trial, current use of aspirin or another antiplatelet drug, recent incidence of stroke and recent or pending cardiac surgery.

Patients were randomized to receive 81 mg (709 individuals), 326 mg (708), 650 mg (715) or 1,300 mg (717) enteric coated aspirin daily, in addition to placebo. No separate placebo arm was included in the study. Follow up was conducted 30 days and three months after surgery.

In an efficacy analysis in 1,116 patients, strokes were observed in 18 (3.2%) patients taking low-dose acetylsalicylic acid, compared to 38 (6.9%) on high-dose levels. Similarly, incidences of MI were recorded in five patients (.9%) on low-dose aspirin and 18 (3.3%) on high-dose; for total mortality, nine (1.6%) and 12 cases (2.2%), respectively.

"Compared with low-dose acetylsalicylic acid, high-dose...increased the risk of the three composite definitions of treatment failure by 25% to 38% in all patients, and more than doubled the risk of these events in the efficacy analyses," Taylor et al. report. Within the "low" and "high" dose categories, no "significant" differences were detected between the 81 mg and 325 mg levels and the 650 mg and 1,300 mg groups.

Incidence of haemorrhagic stroke was lower in the 81 mg and 325 mg groups, but not to a significant degree; other bleeding complications, such as gastric upset, spontaneous bleeding and haematemesis, were "unrelated to dose," the authors state.

Taylor et al. caution that although the trial "supports the use of low-dose acetylsalicylic acid in patients scheduled for carotid endarterectomy," the data "must not be over-generalized."

"The dose required to prevent perioperative strokes in surgical patients may differ from that required for stroke prevention in long-term medical management of patients at risk of stroke," the researchers state.

In an accompanying editorial, Jan van Gijn, University Medical Centre, Netherlands, also questions "whether the results of this short-term trial, in which almost 80% of events were related to a surgical lesion in the arterial wall, apply to the wider perspective of all patients with threatened stroke."

Although he notes the researchers' carefulness, van Gijn maintains that "facts cannot be interpreted in isolation," adding: "Readers will integrate the findings with their own convictions based on their own interpretation of past evidence."

Van Gijn concludes that while the results should "dispel concerns" regarding the effectiveness of low-dose aspirin for stroke prevention compared to high-dose levels, the ACE trial data "may well represent another fluctuation around essentially the same antithromboric effect of any dose of aspirin between 30 mg and 1,300 mg, for any indication."