Meta-analysis of the duration of dual antiplatelet therapy in patients treated with second-generation drug-eluting stents
Selected in The American Journal of Cardiology by D. Milasinovic
D'Ascenzo F, Moretti C, Bianco M, Bernardi A, Taha S, Cerrato E, Omedè P, Montefusco A, Frangieh AH, Lee CW, Campo G, Chieffo A, Quadri G, Pavani M, Zoccai GB, Gaita F, Park SJ, Colombo A, Templin C, Lüscher TF, Stone GW
Am J Cardiol. 2016 Jun 1;117(11):1714-23
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What is known
The quest for optimal duration of dual antiplatelet therapy (DAPT) after stent implantation has faced a dichotomous challenge, balancing the risks of ischemic and hemorrhagic adverse events. Most of the hitherto conducted studies on this subject enrolled patients with different stent types, including bare-metal (BMS) and first-generation drug-eluting stents (DES). Since newer-generation DES have been associated with lower rates of ischemic adverse events, the aim of this meta-analysis was to assess the risk-benefit ratio of prolonged DAPT after implantation of 2nd-generation DES.
- The analysis included 8 randomized trials, with 18,810 patients who received 2nd generation DES - 12,510 everolimus-eluting (EES), 5,768 fast-release zotarolimus (ZES) and 532 biolimus-eluting stents (BES).
- Data from the following short vs. long DAPT regimens were pooled using the random-effects model: ≤ 6 vs. 12 months (5 trials), 6 vs. 24 months (1 trial) and 12 vs. ≥ 30 months (2 trials).
- All-cause mortality was similar in patients with shorter vs. longer DAPT duration (1.8% vs. 2.1%, p=0.31), as were the rates of cardiovascular mortality (1.0% vs. 1.1%, p=0.77), and stent thrombosis (p=0.39) and target-vessel revascularization (p=0.77).
- Longer DAPT was associated with lower incidence of myocardial infarction (MI) (1.7% vs. 2.3%, p=0.03), mainly driven by MI reduction in the subgroup of trials comparing 12 vs. ≥ 30 months DAPT regimens.
- Shorter DAPT decreased the risk of major bleeding (1.0% vs. 1.6%, p<0.001) and this effect was consistent across the subgroups (≤ 6 vs. 12 months, 6 vs. 24 months, 12 vs. ≥ 30 months).
- Meta-regression revealed no significant impact of baseline patient characteristics, including acute coronary syndrome (ACS) at presentation, on the pooled outcomes.
This study seems to first add information to the ongoing discussion about possibly increased mortality risk with longer-term DAPT, and to secondly provide basis for the decision-making process regarding the optimal DAPT duration in patients treated with 2nd-generation DES.
First, although the results of the present meta-analysis do not support association of longer DAPT with increased all-cause mortality in patients with 2nd-generation DES, it should be noted that mortality data from DAPT trial were not included in this analysis. Moreover, in the light of the excess major bleeding associated with longer DAPT, a possibility of increased mortality risk should not be neglected, despite the reports attributing the higher mortality in the longer DAPT arm of the DAPT trial to uneven distribution of history of cancer between the two study groups.
Secondly, considering the elevated bleeding risk for any prolongation of DAPT and MI reduction only with substantially longer DAPT (i.e. over 2 years), and the sensitivity analysis showing no difference in outcomes between EES and fast-release ZES, the optimal duration of DAPT in patients treated with 2nd-generation DES may largely depend on non-stent-related factors, such as the risk of bleeding and the nature of coronary artery disease (CAD). Since CAD is heterogeneous both in its presentation (ACS vs. stable angina) and morphologic complexity, when deciding upon DAPT duration these different aspects of the underlying CAD and the bleeding risk of an individual patient may need to be taken into consideration.
Do you use individual risk profiling to assess ischemic vs. bleeding risks in your everyday practice? If yes, what approach/calculator do you use? If not, for how long is DAPT regularly prescribed in your center?