Post DES Dual Antiplatelet Therapy Still under Debate

The NIPPON trial (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was a randomized study comparing a short dual antiplatelet therapy scheme (6 months) vs. a prolonged scheme (18 months) in patients receiving the Nobori drug eluting stent (Terumo, Tokyo, Japan) with a biodegradable abluminal polymer.

It included 3,773 patients with chronic stable angina or acute coronary syndrome receiving the Nobori DES, randomized 1:1 to 6 months vs. 18 months of dual antiplatelet therapy (DAPT). Primary end point was a combination of net adverse clinical and cerebrovascular events (NACCE) which included: all-cause mortality, acute myocardial infarction, stroke and major bleeding between 6 and 18 months after DES stenting.

Primary end point occurred in 34 patients (2.1%) receiving a short scheme and in 24 (1.5%) of those under the 18 month scheme; which confirmed non-inferiority for the first group.

Also read: “Dual antiplatelet therapy after EES stenting: 6 or 12 months?

Mortality was 1% with the 6 month scheme vs. 0.4% with the 18 month scheme; infarction rate was 0.2% vs. 0.1% and major bleeding was 0.7% vs. 0.7% respectively.

Estimated NACCE probability resulted lower with 18 month DAPT (HR 1.44, 95% CI: 0.86 a 2.43).

Conclusion

Six month dual antiplatelet therapy resulted non-inferior at 18 months after biodegradable DES implantation. However, these outcomes should be interpreted with caution, since trial design was open and non-inferiority margin was ample. 

Editorial Comment

The combination of a short DAPT and new generation DES with biodegradable abluminal coating should simultaneously reduce thrombotic and bleeding event rates. This was the hypothesis guiding this work and, even though the figures support this idea, we are still far from defining what to do in the clinical practice. 

One of the problems of this study was the low rates of events, which reduced its statistical power. This could be explained by the low difficulty of procedures (stent mean length was only 20 mm and 66% of patients received >3mm diameter stents).

This tendency of enrolling low risk patients was observed in all the studies exploring the short scheme DAPT hypothesis.

Also read: “Last generation DES present better results in vein grafts than old DES and BMS”.

Protocol adherence is another problem common to these studies. In fact, in the SECURITY trial (Second Generation Drug-Eluting Stent Implantation Followed by Six-Versus Twelve-Month Dual Antiplatelet Therapy) 33.8% of patients that were supposed to receive only 6 months DAPT, for some reason, continued up to 12 months.

For the ITALIC-plus trial, the lack of adherence was seen in almost 20% of the total number of patients.

Another problem of this kind of studies is that bleeding events are considered only from the moment the groups are divided (for instance, in the present study, bleeding events occurred in the first 6 months were not taken into account, and both arms were receiving DAPT) Most of major bleeding events occurred at the beginning, which is why, proceeding this way, you are actually choosing patients that tolerate DAPT well and you are limiting the chance to see any differences.

Given the above stated, it seems DAPT should be tailored to each patient according to our clinical judgement, instead of being left to arbitrary criteria magically surged from some trial.

Original title: Dual Antiplatelet Therapy for 6 vs. 18 Months after Biodegradable Polymer Drug-Eluting Stent Implantation.

Reference: Masato Nakamura et al. J Am Coll Cardiol Intv 2017;10:1189–98.

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