Low-dose aspirin as effective and safer than high-dose after PCI

Low-dose aspirin appears to be as effective as — but considerably safer than — the higher doses favored by most American cardiologists for prevention of recurrent cardiac events after percutaneous coronary intervention.

They presented a retrospective observational analysis of the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events in Patients Undergoing Percutaneous Coronary Intervention (PCI-CURE) trial database, which concluded that the adjusted risk of major bleeding within 8 months after the procedure was 2.2-fold greater in patients on aspirin at a dosage of at least 200mg/day, compared with those on 100mg/day or less.

This analysis suggests low-dose aspirin may be superior with regard to a lower rate of serious bleeding compared to high-dose aspirin, and with similar efficacy in terms of death, MI, and stroke.

Moreover, these PCI-CURE findings are supported by two other large observational analyses in patients with acute coronary syndrome that reached the same conclusions. One involved nearly 9,200 participants in a study of the failed oral glycoprotein IIb/IIIa inhibitor lografiban. The other included more than 12,500 patients in a clopidogrel trial.

We personally have increasingly been prescribing low-dose aspirin after PCI because of the data from these three observational studies.

We stressed that observational data such as these must be considered hypothesis generating. But a large, prospective, randomized clinical trial is well underway under the leadership of colleagues at McMaster. The seventh Optimal Antiplatelet Strategy for Interventions/Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Trial (OASIS-7/CURRENT) is randomizing 14,000 patients with unstable angina or non ST-elevation MI to either 300- or 600-mg loading dose of clopidogrel and low- or high-dose aspirin. Results should be available in 12-18 months.

The PCI-CURE analysis involved 2,658 patients with acute coronary syndrome on four continents who underwent PCI. Aspirin dosing was left to physician preference, which in Europe strongly favored the use of 100 mg/day or less in accord with the latest European Society of Cardiology practice guidelines. In contrast, the great majority of American cardiologists prescribed at least 200 mg/day — as recommended in current American College of Cardiology/American Heart Association guidelines.

When there’s such a practice difference between Europeans and Americans, it tells us that perhaps we need more data.

At 8-month follow-up in PCI-CURE, the major bleeding rate was 1.9% in the low-dose aspirin group, compared with 3.9% with high-dose therapy. The 2.2-fold increased risk in the high-dose group was derived after adjusting for potential confounders, including age, gender, weight, hypertension, and use of clopidogrel versus placebo.

The combined end point of cardiovascular death, MI, or stroke was 7.1% in the low-dose aspirin group and 8.6% with high-dose therapy, a nonsignificant difference.