Background The potential benefit of long-term dual antiplatelet therapy (DAPT) for secondary prevention of atherothrombotic events is unclear. Data from different randomized controlled trials (RCT) using different agents in different subgroups showed inconsistent results. Methods We performed a systematic review and meta-analysis from RCTs that tested different prolonged durations of DAPT for secondary prevention. Long term DAPT arm was defined as those receiving DAPT for more than 12 months. Long-term aspirin arm was defined as those receiving either Aspirin alone long term or DAPT for less than 12 months. Results The use of long term DAPT was associated with a significant decrease in composite of death, myocardial infarction (MI) and stroke (6.08% vs. 6.71%; Odd Ratio OR= 0.86 [0.78–0.94]; P=0.001). This reduction of death, MI and stroke was mainly noticed in patients with prior MI or stroke, but not with PAD or multiple risk factors. The reduction was seen with post PCI patients with prasugrel and only in those with prior MI with clopidogrel and ticagrelor. Long-term use of DAPT was associated with significant increase in major bleeding (1.47% vs. 0.88%; OR= 1.65 [1.23 – 2.21]; P=0.001). Conclusion Long-term use of DAPT for secondary prevention is associated with lower risk of death, MI and stroke beneficial especially in patients with prior MI and stroke, but it is associated with increased risk of bleeding. Prolonging DAPT requires careful assessment of the trade-off between ischemic and bleeding complications and should probably reserved for patients with higher risk for atherothrombotic events.

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