Aspirin is the mainstay of treatment for primary and secondary prevention of cardiovascular disease and secondary prophylaxis of cerebrovascular disease. Following chronic use, clinical case reports have indicated a “rebound effect” characterized by an increase in platelet reactivity to a level greater than baseline prior to therapy which could place patients at risk of recurrent ischemic events.

The purpose of this study was to determine if a rebound effect exists upon abrupt discontinuation of long term aspirin therapy.

Healthy men and women were screened for variables that could affect platelet function and stroke risk. Two baseline visits were conducted before participants were placed on 324mg of aspirin. Blood samples were collected on the 90 ± 3 day of treatment, and post discontinuation of aspirin on 1, 3, 5, 7, 14, 21, and 28 days after completing treatment. Whole blood aggregometry was completed utilizing collagen 1mcg/mL, 5 mcg/mL and arachidonate 0.5 mM agonists. Aggregometry and thromboxane testing were performed at each visit and testing for COX-1 receptor density was performed at baseline and the 90-day visit.

Twenty-six volunteers participated in this study; mean duration of treatment was 90.58 days. Percent of COX-1 positive platelets and COX-1 mean fluorescence intensity both decreased significantly from baseline (p=0.02, p=0.03, respectively). Seventy-six percent of participants showed a rebound effect in either collagen 1mcg/mL or arachidonate and rebound aggregation was statistically significant as compared to baseline for these agonists as well (p<0.001, p=0.002, respectively). The greatest prevalence for rebound effect to collagen 1mcg/mL was seen at day five post aspirin discontinuation (43%) and at days five and fourteen for arachidonate (33% each).

Abrupt discontinuation of aspirin produced a mixed effect in healthy volunteers and significant rebound in platelet aggregation occurred in 76% of patients within 1-2 weeks after discontinuation.