No difference in ischaemic risk or bleeding with low vs high-dose aspirin for secondary prevention: Lessons and questions from the ADAPTABLE trial

Low-dose aspirin (81 mg daily) was associated with similar rates of ischaemic events and bleeding events as high-dose aspirin (325 mg daily) in preventing stroke, myocardial infarction (MI), or death in patients with known atherosclerotic cardiovascular disease (ASCVD) according to the findings of the ADAPTABLE trial, but a high degree of cross over adds complexity to the results [1,2].

Prof. William Schuyler Jones (Duke Clinical Research Institute, NC, USA) presented the ADAPTABLE study (NCT02697916), which aimed to compare the effectiveness of 2 doses of aspirin at preventing major adverse cardiac events (MACE) in patients with ASCVD (defined as a history of prior MI, prior coronary angiography showing ≥75% stenosis of at least 1 epicardial coronary vessel or prior coronary revascularisation procedures, or history of chronic heart disease).

The ADAPTABLE trial was a pragmatic, open-label, patient-centred, randomised clinical trial conducted in 15,076 patients with ASCVD within the National Patient-Centered Clinical Research Network (PCORnet). Participants (n=15,067) were assigned to take either 325 mg of aspirin daily (n=7,536) or 81 mg of aspirin daily (n=7,540). The primary outcome was a composite of death from any cause, hospitalisation for MI, or hospitalisation for stroke.

After a median follow-up of 26.2 months, 590 (7.28%) participants in the 81 mg dosage arm and 569 (7.51%) participants in the 325 mg dosage arm had reached the primary endpoint (HR 1.02; 95% CI 0.91–1.14). The primary safety endpoint was hospitalisation for major bleeding. Less than 1% of the participants in either group experienced a significant bleed (53 or 0.63% in the 81 mg daily dose group and 44 or 0.60% in the 325 mg daily dose group). Participants could switch their dose of aspirin during the study if they chose to do so. Among the lower dose group, 7.1% of patients chose to switch to the higher dosage, while among the higher dose group, 41.6% chose to switch to the lower dose.

The researchers concluded that there were no observed differences in cardiovascular events or major bleeding between higher and lower dose of aspirin in patients with ASCVD. These findings stand in contrast to prior randomised trials in ACS (e.g. OASIS-7), which observed higher bleeding rates with high versus low dose aspirin. In this context, the high rate of cross over, particularly from higher to lower dose treatment, is an important limitation of the study.

1. 
   
   1. Jones WS. Aspirin Dosing: A Patient-centric Trial Assessing Benefits And Long-term Effectiveness Trial (ADAPTABLE). ACC 2021 Scientific Session, 15–17 May.
   2. Jones WS, et al. N Engl J Med 2021;384:1981-1990.

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Posted on 9 July, 202118 March, 2024