Short DAPT After DES: P2Y12 Monotherapy Is in, Aspirin Is Out!

Cindy L. Grines; J. Jeffrey Marshall

Disclosures

Eur Heart J. 2019;40(31):2605-2606. 

The duration of dual antiplatelet therapy (DAPT) after drug-eluting stents (DES) has been the subject of intense scrutiny for decades. Initially after FDA approval of first-generation DES, the DAPT strategy was 3–6 months to theoretically allow re-endothelialization of struts. However, after an explosion of DES use by less experienced operators and its use in off-label subsets of patients, it became apparent that rates of late DES thrombosis were alarmingly high. This was thought to be due to unawareness of the importance of DAPT, resulting in premature discontinuation, inadequate stent deployment techniques, and inflammatory durable polymers on first-generation DES. Accordingly, recommendations were revised to extend the duration of DAPT for a full year and educate healthcare providers.[1]

However, DES technology has evolved to biocompatible, anti-thrombotic, or bioabsorble polymers along with thinner struts. Subsequently, late stent thrombosis rates have plummeted,[2] trials have shown the safety of shorter duration of DAPT,[3]and updated guidelines in the USA[4] now recommend 6 months DAPT after DES for stable ischaemic patients and 12 months for patients with acute coronary syndromes (ACS; allowing shorter duration in patients at high risk of bleeding)

Given continued refinement in stents, newer P2Y12 agents, and better stent deployment techniques, investigators have been exploring further shortening of the duration of DAPT. In the past, 'short DAPT' referred to dropping the P2Y12 agent due to its expense and perceived risk of bleeding compared with aspirin alone. More recently, there has been interest in shortening DAPT duration by stopping aspirin and using P2Y12 monotherapy, since these agents have more predictable effects and may have reduced risk of gastrointestinal bleeding compared with aspirin.[5]

Two studies were presented at the American College of Cardiology meeting this year. STOPDAPT-2 randomized 3009 patients who had intravascular ultrasound (IVUS) or optical coherence tomography (OCT) stent optimization to receive 1 month DAPT followed by aspirin discontinuation and continued clopidogrel monotherapy, vs. 12 months of DAPT.[6] Clopidogrel monotherapy at 1 month was associated with reduced bleeding [0.4% vs. 1.5%, hazard ratio (HR) 0.26, 95% confidence interval (CI) 0.11–0.64] with no difference in ischaemic endpoints at 12 months follow-up. Similarly, the SMART-CHOICE trial randomized 3000 patients receiving current generation DES to either 3 months DAPT (after which aspirin was discontinued and patients remained on P2Y12 monotherapy) vs. 12 months DAPT.[7] Again, bleeding was reduced (2.0% vs. 3.4%, P = 0.02) with P2Y12 monotherapy and ischaemic events were similar.

Although these studies are promising, some have questioned whether aspirin can be safely discontinued in higher risk patients such as those undergoing complex percutaneous coronary intervention (PCI). To help answer that question, in this issue of the European Heart Journal, Serruys et al. published a subgroup analysis of complex PCI from the Global Leaders trial which randomized 15 000 patients to 1 month DAPT following by discontinuation of aspirin but continuing ticagrelor monotherapy for 24 months, vs. 12 months DAPT.[8] Complex PCI (multivessel, more than three stents, stent length >60 mm, or two stent bifurcation lesions) was performed in 4570 patients. As expected, complex PCI patients had a higher risk of both bleeding and ischaemia, but appeared to benefit from discontinuation of aspirin at 1 month and continuing long-term ticagrelor monotherapy. Interestingly, despite 2 years of ticagrelor, the advantage observed in reduction in myocardial infarction and revascularization occurred within the first year, and could not be attributed to differences in stent thrombosis. These findings are somewhat reassuring, but have to be considered in light of the fact that the primary endpoint of the overall trial was negative,[9] and this report is of a post-hoc analysis of a non-pre-specified subgroup. The need for 2 years of ticagrelor monotherapy was not of benefit, and whether patients with ACS can shorten the duration of DAPT remains unproven.

Importantly, the TWILIGHT study will address some of these outstanding issues.[10] TWILIGHT enrolled 9000 high-risk patients with successful DES, treated with low-dose aspirin and ticagrelor, with an uncomplicated course at 3 months. Patients were then randomized to either placebo or low-dose aspirin, with continuation of ticagrelor for an additional 12 months. The primary endpoint of Bleeding Academic Research Consortium (BARC) Types 2, 3, or 5 bleeding and the secondary ischaemic endpoint of death, non-fatal myocardial infarction, or stroke will be measured at 12 months.

In conclusion, there is increasing evidence of the safety of discontinuing aspirin 1–3 months after uncomplicated DES, with continuation of P2Y12 monotherapy, especially if IVUS or OCT confirms optimized stent results. Whether this strategy is safe in patients at highest risk of stent thrombosis (ACS or complex PCI) remains uncertain.

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