Twelve or 30 Months of Dual-Antiplatelet Therapy after Drug Eluting Stents
Selected in The NEW ENGLAND JOURNAL of MEDICINE by G. Harris
Laura Mauri, Dean J. Kereiakes, Robert W. Yeh, Priscilla Driscoll-Shempp, Donald E. Cutlip, P. Gabriel Steg, Sharon-Lise T. Normand, Eugene Braunwald, Stephen D. Wiviott, David J. Cohen, David R. Holmes, Mitchell W. Krucoff, James Hermiller, Harold L. Dauerman, Daniel I. Simon, David E. Kandzari, Kirk N. Garratt, David P. Lee, Thomas K. Pow, Peter Ver Lee, Michael J. Rinaldi, and Joseph M. Massaro
N Engl J Med 2014; 371:2155-2166
LinkAccess the abstract
The DAPT study was designed to answer the question of added benefit and risk in the continuation of both aspirin and a thienopyridine vs. aspirin alone for another 18 months, after completion of an initial 12 month period on DAPT (aspirin plus either clopidogrel or prasugrel) in patients who received a drug eluting stent.
Patients who did have a major cardiovascular or cerebrovascular event, stent thrombosis, or moderate or severe bleeding in the first year and were non-compliant on their treatment were excluded from the trial.
This study included patients with both stable and unstable coronary artery disease. There were no significant differences in the baseline characteristics of the two groups.
The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 months to 30 months.
The primary safety endpoint was moderate or severe bleeding.
- There was a significant decrease in the not only the incidence of stent thrombosis; continuation arm (0.4%) vs. the placebo arm (1.4%) (P<0.001),
- but also major cardiovascular and cerebrovascular events (4.3% vs. 5.9%; P<0.001).
- The incidence of myocardial infarction was lower in the continuation arm (thienopyridine group) (2.1% vs. 4.1%) (P<0.001).
- HOWEVER, there was an increased all cause mortality in the continuation arm (thienopyridine group) (2.0% vs. 1.5%) (P=0.05).
- The continuation arm also demonstrated an increased incidence of bleeding (2.5% vs. 1.6%), (P=0.001).
The two main issues concerning benefit are, protection against stent thrombosis and overall 2e prevention of the underlying coronary artery disease.
An interesting finding is the very significant increase in myocardial infarction and stent thrombosis for the 1st three months after the thienoprydine cessation. Is there a rebound effect? Should this be investigated independently (including the possibility of some form of bridging therapy)?
Despite the higher rate of bleeding in the thienoprydine continuation arm, it was still slightly lower than the expected rate when the trial was designed.
The all cause mortality was not a 1e endpoint in itself, and thus lends itself to the associated statistical errors, and was just about statistically significant (P=0.05). I think it should be viewed as such (chance), however this space needs to be watched closely.
It is important to note that this is a highly selective patient population. Patients were excluded not only because of a high bleeding risk, but also because of a high ischaemic risk (eg. if a patient had a particular stent inserted into a left main lesion).
As no major benefit in 6 months vs 12 months of dual antiplatelet therapy has been demonstrated, should the question not be, 6months vs 30 months?
In my opinion, the DAPT trial demonstrated probable (and not possible) benefit of dual antiplatelet therapy in this subset of patients and therefore should be considered in this setting (class IIa). Especially high risk patients such as those with diabetes mellitus.