Abstract 4546: Will Long-Term Dual Antiplatelet Therapy Prevent Adverse Events Related to Drug-Eluting Stents? Projections Based on a Markov Model
Background Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel is recommended to prevent late stent thrombosis associated with drug-eluting stents (DES). Controversy exists, however, over its efficacy and duration.
Methods We developed a Markov model to quantitatively model clinical data from a meta-analysis of stent trial results (Stone et al. NEJM 2007; n=2,633) to predict the effect of DAPT on restenosis, thrombosis and death/MI with DES. The model mirrors the underlying dynamic processes involved in physiological responses to stenting, and yields transition rates for restenosis, stent thrombosis and final outcomes (death/MI), and estimates of the fraction of patients at higher than average risk for adverse complications post-stenting. The frequency of events (in percent) in the low-and high-risk groups is summarized in the Table⇓. The impact of DAPT on the frequency of events in the high-risk group is also shown under two assumptions: 50% (conservative model) and 100% (aggressive model) reduction in the kinetic rate of thrombosis.
Results The model identified a high-risk group comprising 8% of patients experiencing 81% of restenoses at 1 yr and 68% of thromboses at 4 yrs. Outcome events were 1–2 orders of magnitude higher in the high-risk group. DAPT reduced thrombosis substantially but slightly increased restenosis. However, death/MI was reduced by 11% and 8% (conservative model) and by 23% and 17% (aggressive model) at 1 yr and 4yrs.
Conclusions Kinetic modeling identifies a high-risk group comprising approximately 10% of DES patients experiencing 70 – 80% of outcome events. Use of DAPT in these high-risk patients is projected to prevent thrombosis, but has little effect on death/MI, thereby suggesting progression of disease in non-target lesions as the likely cause of long-term clinical events post-DES. Markov modeling is a promising way to assess the effectiveness of DAPT especially in situations where clinical trials are impractical.