Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

Abstract

BackgroundDual antiplatelet treatment has been shown to reduce recurrence of stroke compared to aspirin alone when initiated early after an acute stroke. The effect of clopidogrel and aspirin versus aspirin alone within 72 hours of acute cerebral ischemia from atherosclerosis has not been well studied. MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, not receiving thrombolysis or thrombectomy in 222 hospitals in China. Patients were randomly assigned within 72 hours after symptom onset in a 1:1 ratio, to receive clopidogrel (300mg on day 1, 75mg daily on days 2-90) and aspirin (100-300mg on day1, 100mg daily on days 2-21), or clopidogrel placebo and aspirin (100-300mg on day1, 100mg daily on days 2-90). There was no interaction between this component of the factorial trial design trial and a second part that tested immediate vs delayed stain treatment and is reported separately. The primary efficacy outcome was a new stroke, and the primary safety outcome was moderate-to-severe bleeding, both within 90 days. ResultsA total of 6100 patients were enrolled, 3050 assigned to each trial group. The qualifying event for enrollment was TIA in 13%. Approximately 13% of patients were assigned to a treatment group within 24 hours and 87% were assigned between 24 and 72 hours of onset of stroke. A new stroke occurred in 222 (7.3%) in the clopidogrel-aspirin group, and 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 (0.9%) and 13 patients (0.4%), respectively (hazard ratio, 2.08; 95% CI, 1.07-4.04, P=0.03). ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin initiated within 72 hours of onset was superior to aspirin alone in reducing the risk of new stroke at 90 days but was associated with a low but increased risk of moderate-to-severe bleeding.

A REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT)

“…A proper evaluation of patients’ hemorrhagic risks including an assessment of the volume of ischemic lesions might minimize hemorrhagic complications of DAPT. The exact window for DAPT start after an ischemic event is yet to be defined, INSPIRES and a sub-analysis of POINT showed that DAPT was still beneficial if administered within 72 hours from symptom onset 9,29 , thus a delayed treatment start might be considered in specific cases. Mortality was not a concern in our cohort, and the rate of vascular death was comparable to RCTs 6-8 .…”

“…Specifically, CHANCE and POINT assessed the efficacy of 21- and 90-day clopidogrel/aspirin DAPT in patients with NIHSS score ≤3 and ABCD 2 score ≥4 6,7 , while THALES assessed the efficacy of 30-day ticagrelor/aspirin DAPT in patients with NIHSS score ≤5 and ABCD 2 score ≥6 or symptomatic intra/extracranial arterial stenosis 8 . Recently, INSPIRES confirmed the efficacy and safety of 21-day clopidogrel/aspirin DAPT after an ischemic event of presumed atherosclerosis origin in patients with NIHSS score ≤5 and ABCD 2 score ≥4 who started the treatment within 72 hours from symptom onset 9 .…”

Dual Antiplatelet Therapy for the Acute Management and Long-term Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack, An Updated Review

“…Among the participants, 82% had ≥50% symptomatic arterial stenosis, and 87% were randomized at a later time window (compared to CHANCE and POINT) at 24-72 h after symptom onset. DAPT was associated with both a significant decrease in recurrent stroke (7.3 vs. 9.2%) and a significant increase in moderate to severe bleeding (0.9 vs. 0.4%) [29].…”

“…A study from hospitals in the USA found that 47% of minor stroke patients did not receive DAPT, whereas 42.6% of patients with non-minor stroke received DAPT upon discharge [28]. There are some justifiable reasons for prescribing DAPT in strokes with NIHSS > 3, such as in cases of symptomatic large artery atherosclerosis, supported by the recently published INSPIRES trial [29] (see Section 4). We believe that DAPT may be prescribed for strokes with NIHSS > 3 on a case-by-case basis.…”

A Review on the Mechanisms of Stroke-Induced Muscle Atrophy

“…Stroke survivors may experience difficulties eating secondary to weakness in swallowing muscles and/or have impaired nutrient absorption, leading to inadequate protein intake and malnutrition [6]. The lack of essential amino acids, the building blocks of proteins, further exacerbates muscle protein breakdown.…”