Dual antiplatelet therapy: More the better?

Dual antiplatelet therapy: More the better?

Dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel, prasugrel etc) is currently recommended for at least 12 months after implantation of a drug eluting stent (DES) following a percutaneous coronary intervention (PCI). But there have been instances of late stent thrombosis and very late stent thrombosis after DES implantation. Hence the DAPT study (Dual Antiplatelet Therapy) sponsored by the Harvard Clinical Research Institute sought to look at benefits of dual antiplatelet study at 30 months after implantation of a drug eluting stent and bare metal stent. The study results were presented at the American Heart Association meeting 2014.

The study enrolled patients 72 hours after stent placement and were given dual antiplatelet agents for 12 months. Those without a bleeding or ischemic complication at 12 months were randomized to receive either dual antiplatelet (DAPT) agents or a matching placebo for the next 18 months.
In the DES PCI group there were around ten thousand patients with half each randomized to either dual antiplatelet agents or placebo. About one third of them were diabetics and a quarter were smokers. ST elevation myocardial infarction was present in only one tenth of the patients enrolled, while one third had non ST elevation acute coronary syndrome and a little over one third had stable angina. Major adverse cardiac and cerebrovascular events (MACCE) was significantly lower in the DAPT arm compared to placebo. Myocardial infarctions and stent thrombosis were lower in the DAPT group while all cause mortality was higher, mostly due to increase in non cardiovascular deaths. GUSTO moderate and severe bleeding was also higher with DAPT.

In the BMS PCI group there were only around one thousand and five hundred patients. MACCE was similar in those who had DAPT compared to those on placebo. There was no difference in the all cause mortality, stroke or stent thrombosis. But GUSTO moderate and severe bleeding was higher with DAPT.

It is notable that in those who had PCI with bare metal stents there is no added advantage of continuing dual antiplatelet therapy and there is potential harm in terms of increased bleeding. Even though myocardial infarction and stent thrombosis in those with DAPT after DES are lower, it also comes at a price of higher bleeding. The higher mortality with DAPT in DES group which is attributed to deaths due to cancer and bleeding is also of concern. It remains to be seen how much the trial results would change our practice patterns, though at first look it does not seem to suggest the need for a major change.

The results would not apply to those with ischemic complications within one year and those with bleeding complications in that period as these were exclusion criteria. Those would ischemic complications may certainly benefit from extend DAPT while those with bleeding complications may not.