Elvin Kedhi: Dual antiplatelet therapy in patients with STEMI—is longer treatment needed?

As a trainee I was always fascinated by the impact of a percutaneous coronary intervention (PCI) in patients with an ST-elevation myocardial infarction (STEMI). In a matter of minutes a patient would become stable and miraculously free of pain, and have a drastic improvement in life expectancy. Since then, primary PCI treatment has been one of my favourite topics, and not without reason. Despite the fact that more than half of catheterization laboratory patients undergoing PCI are being treated for acute coronary syndromes (ACS), including MI,1 many questions regarding this treatment still remain unaddressed. The recommended duration of dual antiplatelet therapy (DAPT) after primary PCI is one of them.

Over the past few decades, the duration of DAPT has seen drastic changes, most of which have not been driven by evidence, but by expert opinion. DAPT was initially used to reduce thrombotic events after stent implantation. The high rate of stent thrombosis (ST) with first generation drug eluting stents (DES) prompted longer durations of DAPT usage (12 months). On the other hand, the practice of using longer DAPT regimens to reduce overall thromboembolic events in MI patients, independently from ST protection, has gained ground over the past few years. However, DAPT usage is strongly associated with a significant increase in bleeding,3 including life threatening bleeding.

Therefore two major questions exist:

  1. Do we need DAPT as a protection from thromboembolic events originating elsewhere than the stented lesion?
  2. What is the optimal duration for DAPT in patients undergoing PCI with a modern drug eluting stent to reduce device related adverse events?

Despite large scale trials evaluating the role of longer DAPT regimens in post MI patients showing some benefit for longer DAPT in reducing cardiovascular events, these reductions came with a high price in bleeding, which in turn is strongly related to mortality.4 Indeed, in most of these studies the number needed to harm (major or life threatening bleeding) is lower than the number needed to treat (reduction in thrombotic events).

Furthermore, it has become evident that the progression of coronary atherosclerotic plaque before causing an MI follows a sequence of serial ruptures and healings, a process that progresses over years and lasts a lifetime. Considering the high risk of bleeding and its impact on mortality, which in turn increases with age, it is unfortunately unthinkable that DAPT could offer a logical lifelong solution to reducing CV events deriving from atherosclerosis progression. While from a device perspective, patients with STEMI have shown similar outcomes to all-comer patients, and therefore there is no reason why these patients should require longer DAPT regimens.

With this in mind, we designed and performed the DAPT-STEMI trial. Since it was the first trial to test a shorter DAPT regimen in patients with STEMI, it was a difficult trial to perform. Indeed, at the time this trial was initiated, the interventional cardiology community had for years strongly promoted the use of 12 month DAPT regimens. It therefore took enormous efforts to convince the participating physicians, as well as general physicians, to be open to patient enrollment and randomisation (at six months). However, after long scientific debates, during which the current evidence (or the absence of it) around longer DAPT regimens was scrutinised, we were able to create a dedicated group of international investigators. Thanks to their perseverance and dedication, this trial was successfully completed.

Indeed, as expected we found that based on a net patient oriented outcome, a six month DAPT regimen is equally safe. While our trial is too small to give insights into each of the composites of the primary endpoint, considering the era in which it was designed and performed, a larger trial would have been practically impossible and out of reach of an investigator driven trial.

Although it may not be sufficient to change current guidelines, we are particularly glad that we could provide a well founded answer to our patients that shorter DAPT regimens are safe even after STEMI, if  clinically needed. Furthermore, based on the results of this trial we are able to keep this research path open for larger randomised trials to take place, which will hopefully establish the optimal duration of DAPT after primary PCI.

Elvin Kedhi, cardiologist, Isala Hartcentrum, Isala Klinieken, Zwolle, Netherlands.

Competing interests: See linked research paper.


[1] Dehmer GJ, Weaver D, Roe MT, et al. A Contemporary View of Diagnostic Cardiac Catheterization and Percutaneous Coronary Intervention in the United States. A Report From the CathPCI Registry of the National Cardiovascular Data Registry, 2010 Through June 2011. J Am Coll Cardiol 2012 Nov 13;60(20):2017-31. http://www.onlinejacc.org/content/60/20/2017.full

[2] Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014 Dec 4;371(23):2155-66. https://www.ncbi.nlm.nih.gov/pubmed/25399658

[3] Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015 May 7;372(19):1791-800. https://www.ncbi.nlm.nih.gov/pubmed/25773268

[4] Palmerini T, Bacchi Reggiani L, Della Riva D, et al. Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting. J Am Coll Cardiol 2017 Apr 25;69(16):2011-2022. https://www.ncbi.nlm.nih.gov/pubmed/28427576