DAPT in DES Patients of Twelve Months Dual Antiplatelet Therapy after Drug-eluting Stents – Too Long, too Short or Just Right?

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Summary

DAPT in DES Patients – a Moving Target!

The main limitation of BMS was an exaggerated inflammatory healing response, leading to excessive neointimal proliferation and restenosis. Clinically, this led to around 10 % of patients representing with recurrent symptoms. Randomised trials demonstrating the dramatic reduction in target vessel revascularisation, due to restenosis, with DES compared with BMS has revolutionised patient care.^7-9 However, the cost of this clinical benefit was a demonstrably higher risk of ST in DES1 versus BMS, which was attritional over time.¹¹ As a result, international guidelines were changed in 2007 to indicate that all patients receiving DES should receive DAPT for “at least 12 months”.¹² The default regimen was even more strongly set, albeit still based upon very little actual evidence.¹²

More recently, however, the continuous iteration of DES design has yielded devices with properties likely to reduce the risk of ST: thinner struts; less, or shorter duration, polymer; more sophisticated drug and dosing profiles. As a result of observational data confirming this notion, second- and third-generation DES (DES 2) have been the focus of a series of randomised trials testing shorter duration DAPT versus longer regimens.^13–20 These trials are disparate in detail regarding type of stent, mix of patient presentation, duration of the DAPT regimens being compared, type of P2Y12 inhibitor and composite primary endpoint.¹⁹ However, they share some common features. First, none were powered to look at ST as a primary isolated endpoint. Second, they generally have demonstrated no advantage of a longer DAPT duration compared with shorter. Furthermore, in many cases, they demonstrated significantly higher rates of major bleeding in the longer DAPT groups.

It is notable that in some randomised trials, the duration of DAPT could be as short as 3 months with some types of DES 216–17 without any disadvantage in terms of ischaemic endpoint. The accumulated body of this evidence has pointed interventionalists towards shorter duration DAPT in DES 2 patients. This is, indeed, reflected in the 2014 ESC guidelines²¹ now recommend DAPT for only 6 months in stable patients receiving DES 2, but stick to 12 months’ DAPT after ACS. A seemingly logical and intuitive evolution in what we all thought we knew about DAPT with modern DES 2 was then challenged by the DAPT trial.