ORLANDO, FLA. — When it comes to prescribing daily aspirin for the prevention or treatment of vascular events, the lowest risk of bleeding complications in a new metaanalysis involving more than 192,000 patients was seen at dosages less than 100 mg/day, Victor L. Serebruany, M.D., reported at the annual meeting of the American College of Cardiology.
The most surprising finding in this massive metaanalysis was not that lower aspirin doses are safer—“You don't need to be a rocket scientist to realize that,” he said—but rather, that the bleeding risk climbed dramatically with doses even in the moderate range of 100-200 mg/day. The analysis involved 31 randomized controlled trials published since 1988.
“We do not know if 75 mg/day of aspirin is better or worse than 325 mg in terms of efficacy, because there has been no direct comparative trial. However, now we know for sure that the lower the dose, the less the bleeding risk … The absolutely practical, simple lesson is, if you are not sure that efficacy is actually different, use as low a dose as possible,” stressed Dr. Serebruany, owner of HeartDrug Research, LLC, of Towson, Md.
Of the 31 trials included in the metaanalysis, 9 featured low-dose aspirin arms. Eight examined the impact of moderate-dose aspirin, defined by Dr. Serebruany as 100-200 mg/day. Nineteen had high-dose aspirin arms, involving daily doses greater than 200 mg.
The rate of major bleeding was around 1.5% in patients on low- or moderate-dose aspirin, rising to more than 5% in the high-dose group. Surprisingly, however, the 0.47% stroke rate associated with moderate-dose aspirin was twice that of the low- or high-dose groups. The 2.7% GI bleeding rate in the moderate-dose group was nearly as great as that in patients on high-dose aspirin and significantly more than the 0.97% rate in patients taking less than 100 mg/day.
Minor bleeding also was common among patients taking 100-200 mg of aspirin daily. As a consequence, the moderate-dose group had the highest rate of total bleeding complications, at 11.3%. This was somewhat greater than the total bleeding rate in patients on high-dose aspirin (just over 9%) and far more than the 3.3% rate in patients on low-dose therapy.
Why so many bleeding complications with moderate-dose aspirin? Dr. Serebruany suspects the answer lies, at least in part, in the use of more stringent adverse event reporting systems in some of the large, recent trials using doses of 100-200 mg/day. In the earlier studies involving high-dose aspirin, minor bleeding often went overlooked.
Dr. Serebruany estimated that at least three in five American men and two in five women over age 45 are taking aspirin. “One of every four patients after an acute vascular event will not develop another vascular event if taking aspirin. It would not be fair to say other antiplatelet agents are less beneficial or more beneficial. They are simply used on top of aspirin,” he said.
The lower-is-better message when it comes to aspirin prescribing is particularly relevant for interventional cardiologists. They often aggressively pile on short-term use of multiple antiplatelet agents, antithrombins, and/or glycoprotein IIb/IIIa inhibitors in addition to moderate- or high-dose aspirin in an effort to minimize the risk of subacute thrombosis in conjunction with stenting.
Dr. Serebruany scoffed at this approach as platelet overkill and urged physicians who prescribe combination antiplatelet and/or anticoagulant therapy to keep the aspirin dose below 100 mg/day.
“If you give 25 mg of aspirin, you have complete platelet inhibition within 10 minutes. This is a fact. So why do you need more? It's probably overprotective,” the physician said.
Besides, Dr. Serebruany added, there's not much evidence that this aggressive, higher-risk antiplatelet strategy on the part of interventional cardiologists is even achieving its purpose.
“The restenosis rate is definitely going down with the use of drug-eluting stents. However, the rate of subacute thrombosis isn't necessarily going down.”