We found that 53 (51%) of recurrent stroke patients discontinue aspirin compared to 30 (28.8%) of the control group with significant statistical difference between both groups. Among patients who stopped aspirin, we found that no stroke occurs when aspirin stopped for 0–7 days, 25 (48%) in period of 8–30 days, 13 (24%) in period of 31–180 days and 15 (28%) in period of > 181 days.
This agrees with Maulaz and colleagues [11] who claimed that the stroke can occur 8–21 days after stopping aspirin use and withholding aspirin for 5–7 days is risk-free. Also, Sibon and Orgogozo [14] mentioned that 4.49% of strokes were related to a recent aspirin discontinuation, but all cases developed between 6 and 10 days after discontinuation (p < 0.0001). Also, Weimar and colleagues [15] reported that stroke was associated with absolute excess risk of 0.77% within 30 days after discontinuation of aspirine + extended-release dipyridamole.
On other hand, Rodriguez and colleagues [1] reported that 10.0% of patients had discontinued recently (31–180 days), and 4.3% had discontinued in the past (181–365 days) and that the risk was higher in patients who had stopped use 1 to 15 days before the event.
These findings can be explained by rebound effect after aspirin withdrawal [16]. The cause of the increased rate of stroke after stop aspirin is a rebound prothrombotic effect [11]. Halting of aspirin results in a rebound effect involving platelet formation and aggregation, thus the increase in events immediately after aspirin is discontinued [1]. Stimulatory effect on platelet basal production of arachidonic acid metabolites occurs when measured 3 weeks after stopping aspirin therapy and suggested the induction of a new platelet population with higher cyclooxygenase activity [17].
We found no significant difference between both groups in relation to stopping statins or antihypertensives; however, there was significant statistical difference between both groups according to history of NSAID use, as 13 (12.5%) of control were found to use NSAIDs; on other hand, only 2 (1.9%) of patients use it, which may suggest a protective role of NSAIDs.
Support this finding Rodriguez and colleagues [1], who mentioned that there was no observed increase in the risk of stroke/TIA among the subgroup of patients who concomitantly took aspirin and non-cyclooxygenase-2 (COX2) non-steroidal anti-inflammatory drugs (NSAIDs), despite a possible interference of NSAIDs with aspirin’s antiplatelet activity.
We found that non-compliance was the major cause of discontinuation in our patients which occur in 32 patients out of 53 patients who stop aspirin. This comes in accordance with Rodriguez and colleagues [1] who claimed that patient nonadherence was the major cause for discontinuation of aspirin therapy which in turn leads to increased stroke risk. On the other hand, Maulaz and colleagues [11] mentioned that the main reasons for stop aspirin were surgery, decision of the treating physician’s that therapy had no clear clinical benefit, bleeding, negligence, and dementia.
We found that patients who stop aspirin for 8–30 days were associated with a very high-risk score, patients who stop aspirin for 31–180 days were associated with a moderate-risk score, and patients who stop aspirin for 181–365 days were associated with a high-risk score with significant statistical difference. Maulaz and colleagues [11] reported that discontinuation of aspirin is a significant risk factor for a cerebral stroke in the 4 weeks after aspirin discontinuation and the mean interval between treatment withdrawal and stroke was 9.5 days. Recent discontinuers (31–180) had a significant greater risk (40%) for ischemic stroke, and past discontinuers (> 180) had a non-significant greater risk (25%) [1].
In our patients, 50% (N = 52/104) showed a moderate NIHSS score. In patients who discontinue aspirin, 47.2% (N = 25/53) showed severe NIH score. These findings indicate that more sever stroke may follow aspirin discontinuation and no previous data to our knowledge deal with this point.
The Oxford classification showed that partial anterior circulation infarct was present in 45 (43.3%) of patients and 41 (39.4%) in the control group. This comes in accordance with Mead and colleagues [18], who found that partial anterior circulation infarcts were present in 34% of stroke patients. Also, Bamford and colleagues [19] reported that partial anterior circulation infarcts were associated with the highest risk of early (within 3 months) recurrence of stroke. The suspected embolic origin of partial anterior circulation and our exclusion of cardiac cause may refer to undiagnosed cardiac patients as paroxysmal AF.
In patients who discontinue aspirin, lacunar infarct was present in 22 (41.5%) according to the Oxford classification. On the other hand, Maulaz and colleagues [11] reported that cardioembolic stroke was the commonest type of stroke associated with aspirin discontinuation. This contradictory may be explained by the different methodology and our exclusion of diagnosed cardiac patients.
Multivariate analysis logistic regression showed that aspirin discontinuation was an independent factor for recurrent stroke; this comes in accordance with previous studies [1, 11].
Limitations of the study include the low number of patients that were included, the need for more investigation for risk factors, and data were limited as to the etiology of the prior strokes. Other limitations were related to the case–control design as differential errors are hard to avoid because the data for the patients and controls is collected under different circumstances. However, both groups were comparable. Also the frequency of aspirin discontinuation may have been underestimated because patients may not report treatment compliance correctly because of confusion, aphasia, and deterioration of consciousness that may occur in acute stroke. Also, patients with nonadherence or dementia may not report drug discontinuation, and the delay between treatment cessation and cerebral infarct may be underestimated for the same reasons.
One of the strengths of our study is the high frequency of MRI investigations contributing to reliable stroke subtyping. The strength is not retrospective, studying many factors not included in most other studies like risk factors, NIH score, and oxford classification.
In conclusion, the discontinuation of aspirin especially for a period of 8–30 days could increase the risk of recurrent ischemic stroke in patients with high and very high-risk factors and we should be aware of the complications of stopping aspirin use. Not to use aspirin at all may be better than to stop it after use. Very high-risk patients must be advised not to stop aspirin and if a must, not more than 7 days. Physicians need to educate patients about the importance of adherence of aspirin therapy.
