24 Apr, 14 | by EBM
recent followup study to the original POISE trial in the lancet, which found that pre-op b-blockers (metoprolol) did not improve post-surgical outcomes after noncardiac surgery in high risk vascular patients (risks outweighed benefits). NEJM had recent article on aspirin (see doi: 10.1056/NEJMoa1401105). in this trial 10K patients from 23 countries at risk for vascular complications (>45yo, with history of at least one of: CAD, PAD, stroke, major vasc surgery, or over age 70 with high risk of CAD) and about to undergo noncardiac surgery were assigned either aspirin vs placebo or clonidine vs placebo. for the aspirin group, they assessed 2 subgroups, those who were not previously on aspirin (initiation stratum, 5628 pts) and those previously on aspirin (continuation stratum, 4382 pts). those in the initiation group were given ASA 200mg just before surgery and 100mg/d after for 30 days. those in the continuation group stopped their regular aspirin 7 days before surgery, then received 200mg aspirin pre-op and then 100 mg/d for 7 days, then continued their regular aspirin regimen. primary outcome=composite of death or nonfatal MI at 30 days. results:
–baseline: age 69, 53% male, 33% with hx of vascular disease, 65% received prophylactic anticoagulation for 3 days post-op
–primary outcome in 7% in the aspirin group and 7.1% in placebo (non-significant)
–major bleeding in 4.6% in aspirin group and 3.8% placebo (significant with HR 1.23)
–no diff between the aspirin strata (somewhat more acute kidney injury in the continuation stratum and decreased risk of stroke in the initiation stratum. no diff in MI
so, rationale for study is that post-surgical period is assoc with MI and with platelet activation (which might predispose to coronary artery thrombosis and might be prevented with ASA). one concern in this study design was that there are some observational data of increased thrombotic risk if stop aspirin before surgery. this was not found in this study. another issue, not commented upon directly, is whether low-dose aspirin is sufficient. this comes up with diabetics. for example, the well-designed POPADAD study (see doi:10.1136/bmj.a1840) looked at very high risk patients (diabetes and peripheral arterial disease) and found that ASA 100mg/d did not prevent cardiovascular events or mortality, and at that time raised the question whether low-dose aspirin was sufficient in diabetics who have really sticky platelets (and, i believe, led to downgrading of am diab assn recommendations from “recommend aspirin” to “consider aspirin”). so, higher dose aspirin, other antiplatelet drug. to me there are a couple of take-home messages: low-dose aspirin is not sufficient to cover high risk patients with noncardiac surgery (and increases bleeding), so should not be used; and it appears to be safe in this large study to just stop the aspirin a few days before surgery, without worrying about rebound thrombosis.
a separate report looked at giving clonidine 0.2 mg just before surgery and then for next 3 days, with rationale that there is marked activation of the sympathetic nervous system during and after noncardiac surgery, and this should be blocked centrally with clonidine. if anything, in this trial clonidine was worse than placebo (signif increase in nonfatal cardiac arrest) and more hypotension (48% vs 37%)