Background and Purpose- 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 (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register 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.
The researchers stratified the 10 randomized trials into one-month (n=6), three-month (n=2) and > than three-month durations (n=2) of anticoagulants (aspirin versus aspirin and clopidogrel). The results suggest the duration of dual antiplatelet therapy might be most appropriate at a month. Depending on a patient`s preferences about ischemic events and major adverse cardiovascular events (NNT for MACE: 59) against an increased risk for major bleeding (NNH: 139), some patients may prefer to receive dual anticoagulation for three months. There does not appear to be any compelling indication to prescribe clopidogrel after a patient is already taking aspirin beyond three months. The authors go on to state that dual antiplatelet therapy is most effective if initiated within 12-24 hours after a minor ischemic stroke or transient ischemic attack. I believe this meta-analysis could inform provider conversations with eligible patients.
This is definitely a primary care issue. We are responsible for a lot of the post-hospitalization care for patients after stroke, and this information is relevant to all of them...BUT I have some methodologic and interpretation reservations. For example, the abstract conclusion that A+C increased bleeding in long-term compared with short-term use. Figure 3 shows that the pooled estimate of increased risk is identical (1.87 vs 1.82) for the two time points. The only thing that is different is the tighter 95% CI in the long-term use. Concluding there is a risk in one time period and not a risk in the other time period, as stated in the abstract, is a misinterpretation of these data.
Useful information in that it reinforces only short-term use of dual therapy in the context of stroke disease.