ASA failure

Abstract

Objective: To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA.Methods: Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years.Results: The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non-ASA failure group (n 5 2,151) in SPS3 (p 5 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61-1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59-1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1-6.9); however, the risk of intracranial hemorrhage was not different. Conclusions:In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only. Classification of evidence:This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke. Some patients with cardiovascular conditions have events while treated with aspirin. This observation, termed aspirin treatment failure, can be due to multiple reasons, including poor adherence and presence of multiple vascular risk factors enhancing platelet activation.1-3 A laboratory resistance to aspirin has also been described in approximately 15%-20% of cerebrovascular patients. 4,5 In these cases, alternate therapeutic approaches could include either replacing or adding another antiplatelet such as clopidogrel to aspirin. 1,6,7 Clinicians will often switch to another antiplatelet such as clopidogrel after a new non-cardioembolic cerebral ischemic event under acetylsalicylic acid (ASA) therapy.7 However, this clinical practice has not been shown to be effective and lacks any direct supportive evidence. In addition, the combination of ASA and clopidogrel is not recommended for long-term secondary stroke prevention in current guidelines, based on lack of proven efficacy and increased hemorrhagic risk. 8,9 Although recent evidence appears to suggest a potential benefit for the combination of ASA and clopidogrel in the acute setting, additional confirmatory evidence is needed.10 Previous studies 11,12 that have assessed the combination of ASA and clopidogrel have not taken into consideration aspirin failure as a potential ...

Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study

“…A post hoc analysis of patients with aspirin failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort suggested the addition of clopidogrel did not result in reduction of vascular events vs continuing aspirin only. 19 Several differences exist between these two cohorts. First, the exact dosage and duration of aspirin use before the index stroke were not known in SPS3 cohort but all participants in our cohort were receiving aspirin for more than 30 days with average dose of 101.3 mg/day at the time of the index stroke.…”

Management gastrointestinaler Blutungen unter Antikoagulation

“…Unter dualer Plättchenhemmung (z. B. ASS + Clopidogrel) steigt das Risiko im Vergleich zur Monotherapie deutlich an [21]. Höher ist das Blutungsrisiko unter Vollantikoagulation mit Vitamin-K-Antagonisten (z.…”

S2k-Leitlinie Gastrointestinale Blutung

“…Bei dualer Plättchenaggregationshemmung steigt das Risiko gastrointestinaler Blutungen in der ASS/Clopidogrel-Gruppe relativ zur ASS-Monotherapiegruppe auf eine HR von 2,7 an [94]. Die dreifache (Triple-) Thrombozytenaggregations-Therapie (TAT, Zugabe von Cilostazol zu ASS und Clopidogrel) und die konventionelle duale Thrombozytenaggregationshemmung (ASS und Clopidogrel) wurden in einer Metaanalyse verglichen.…”