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Optimale Anwendungsdauer einer Therapie mit Aspirin Plus Clopidogrel nach Schlaganfall oder TIA – A Systematic Review and Meta-Analysis

Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack A Systematic Review and Meta-Analysis

Background
The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy.

Methods
Ten randomized controlled trials (15434 patients) were selected using MEDLINE, EMBASE, and the Cochrane CentralRegister of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with
transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and
cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month),and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI.

Results
A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37–0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58–0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60–0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61–0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63–1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71–1.07). Intermediate-term (RR, 2.58; 95% CI,1.19–5.60) and long-term (RR, 1.87; 95% CI, 1.36–2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91–3.62). Excessive all-cause mortality was limited to long-term A+C(RR, 1.45; 95% CI, 1.10–1.93).

Conclusions
Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.

Fazit:

Die duale Plättchenhemmung scheint einen Monat gut zu wirken, aber danach steigt das Risiko für Blutungen, bzw. haben die Patienten ab einem Monat keinen Benefit mehr.

Die besten Effekte treten wohl in der ersten Woche (bzw. einen Monat) nach Ereignis auf.

Fazit Regen:

Wir sehen selten in diesem Zeitraum Schlaganfallpatienten. Möglicherweise TIA-Patienten.
Die Studie ist ein erster Hinweis – ob wir daraus ableiten können, gleich doppelt zu behandeln, ist unklar. Wir bleiben erst einmal zurückhaltend.