At Issue: Debate over DAPT duration endures
Key takeaways:
- Evidence has accumulated that shorter dual antiplatelet therapy duration is appropriate for many patients who undergo PCI.
- Optimal duration of therapy may vary based on patient characteristics and risk factors.
Since the advent of drug-eluting stents, there has been a debate in the intervention community over how long dual antiplatelet therapy should last after PCI.
Cardiologists have to carefully consider the balance between guarding against ischemic risk, which would favor longer-term DAPT, and guarding against bleeding risk, which would favor shorter-term DAPT. The standard has long been 12 months, but that was implemented due to the first generation of DES raising stent thrombosis risk. With the introduction of newer DES that confer less risk for stent thrombosis and more powerful antiplatelet agents, evidence has mounted that a shorter DAPT duration may be best for most patients.
In the ULTIMATE-DAPT trial, presented at the American College of Cardiology Scientific Session in 2024, 1 month of DAPT followed by ticagrelor (Brilinta, AstraZeneca) monotherapy reduced bleeding risk without raising ischemic risk compared with DAPT consisting of ticagrelor and aspirin for 12 months in patients with ACS who underwent PCI. When presenting results of the ULTIMATE-DAPT trial, Gregg W. Stone, MD, professor of cardiology and population health sciences at Icahn School of Medicine at Mount Sinai and director of academic affairs for the Mount Sinai Health System, said there is enough evidence to change guidelines to endorse 1-month DAPT in that population.
Whether shorter DAPT duration is applicable to almost all patients, or whether there are enough factors in play to make the decision more individualized, is still a matter of debate. Healio asked three experts to weigh in with their thoughts.
Deepak L. Bhatt, MD, MPH, MBA
My answer is: I don’t know. I think there is good evidence to continue longer, and I think there is good evidence to go as short as 1 month. And there is some evidence that in between, like 3 months, is good. I think part of the reason that the answer is “it depends” is that it depends on what the comparator is.
If we look at the totality of data over the years, certainly in high-risk patients, such as those with ACS, significant CAD or diabetes, those sorts of patients tend to benefit from longer durations of double therapy vs. aspirin. That we can say is true going back to the CURE trial, for example. More contemporary trials of extended-term DAPT, such as PEGASUS, THEMIS, and THEMIS-PCI, also showed longer-term DAPT is better than shorter term, which led to labeling updates for ticagrelor. There is a fair amount of data from the clopidogrel era and the ticagrelor era. For prasugrel, there are some data, but they do not address the question of duration per se. In addition, the COMPASS trial showed aspirin plus the vascular dose of rivaroxaban (2.5 mg twice daily; Xarelto, Janssen/Bayer) — which we should call double antithrombotic therapy — is better than aspirin alone. We can do better than aspirin alone in patients who are at high ischemic risk and low bleeding risk, especially if they have already tolerated DAPT for a period of time. In patients at high bleeding risk, the strategy of long-term DAPT or double antithrombotic therapy backfires.
What is not clear is whether de-escalation of DAPT after 1 or 3 months to a P2Y12 inhibitor might be the best of all worlds. It is better than aspirin monotherapy and is linked with less bleeding than DAPT or double antithrombotic therapy.
Of all those strategies, which one is the best and for what duration? We don’t really know. We know from the CAPRIE trial, and more recently the HOST-EXAM trial, that clopidogrel is better than aspirin for reducing ischemic events, especially in higher-risk patients needing secondary prevention, and is at least as safe, even a bit safer when it comes to gastrointestinal bleeding. We know from TWILIGHT that ticagrelor monotherapy after an initial 3 months of DAPT also seems to be an acceptable strategy. However, in the THEMIS-PCI trial comparing aspirin/ticagrelor with aspirin only, the curves didn’t really separate until after 1 year. That’s where it gets tricky combining all these datasets.
I certainly think we need more long-term randomized clinical trials assessing de-escalation of DAPT at 1 or 3 months not to aspirin but to a P2Y12 inhibitor. DAPT does beat aspirin long term, but there is a bleeding price to pay. Clopidogrel monotherapy also beats aspirin, not by as much of a margin as DAPT, but with really no bleeding price to pay. Ticagrelor monotherapy as used in the TWILIGHT trial should be expected to beat aspirin in terms of efficacy, but how it would rate in terms of bleeding is a little less certain. The right dosage is also in question. In the absence of new data, I would do 90 mg twice daily the first year and 60 mg twice daily thereafter. So you can make an argument for any variety of approaches. But if you must pick one approach, I would default to DAPT for 3 months, then de-escalate to a P2Y12 inhibitor.
Bhatt is director of the Mount Sinai Fuster Heart Hospital, the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai and a member of the Healio | Cardiology Today Editorial Board.
Robert A. Harrington, MD, FAHA, MACC, FESC
Few areas of clinical decision-making in the contemporary care of patients with CAD have engendered as much controversy and spurred as many meta-analyses as the question of DAPT duration for patients receiving a DES or having presented with an ACS. There are even published viewpoints calling for clearer nomenclature when discussing DAPT, its components, its duration and switching strategies. Authors have criticized both American and European guideline writers as being overly dogmatic in their recommendations regarding DAPT duration, especially following ACS. All of this makes the individual patient decision-making complex and confusing.
It didn’t start out to be so complicated as DES and oral P2Y12 inhibitors were introduced to clinical cardiology care in the 1990s. Initially, randomized clinical trials showed that stent thrombosis was less frequent when using a DAPT strategy of ticlopidine and aspirin compared with aspirin alone or aspirin plus warfarin. Then clopidogrel was shown to be safer than ticlopidine and stent thrombosis with the early drug-eluting stents seemed to be lessened with more prolonged DAPT. Newer, more potent P2Y12 inhibitors were shown to be superior to clopidogrel in patients with ACS, including the large portion of these patients receiving coronary stents, and because the trials demonstrating these benefits extended 9 to 15 months, guideline writers gave use of approximately 12-month DAPT strategies among patients with ACS a class IA recommendation.
Then the questions really started as bleeding among patients with ACS and/or those undergoing PCI emerged as an important clinical consequence of DAPT treatment that was associated with an increased risk for CV complications, including MI and death. Clinical trials started to compare different strategies to reduce this bleeding risk while maintaining ischemic benefits. These strategies included de-escalation from potent to less potent antiplatelet agents, switching from DAPT to single antiplatelet therapy, and shortening duration. Risk scores to help identify patients with high bleeding or ischemic risk were created to help individualize therapies for patients. Newer-generation stents were developed that were less thrombogenic and seemed to require shorter and even less potent courses of DAPT.
So, where does this leave us in individual patient decision-making? Most patients undergoing PCI with DES can probably receive 1 month of DAPT followed by transition to a less-intense antithrombotic strategy, but there are issues that ought to be considered for longer durations, typically 3 or 6 months, of DAPT, including characteristics associated with higher ischemic risk, such as ACS, multivessel disease, complex PCI, diabetes, etc, but lower bleeding risks.
This is a great opportunity for shared decision-making between patients and their physicians as they consider the ischemic and bleeding risks of different antiplatelet treatment strategies.
Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and the provost for medical affairs at Cornell University.
Amar Krishnaswamy, MD
The short answer is yes, I think that’s safe. I think this is primarily the result of evolution in DES technology. The contemporary generation of stents is designed differently. The polymer thickness and types are different than the first-generation stents. The strut thickness is different than the first-generation stents.
As a result of these technical features, as well as contemporary implantation techniques, the worries about late or very late stent thrombosis, which plagued the first generation of DES in the mid-’00s, have fallen out of our conventional thinking as a major risk.
We now have numerous studies demonstrating the safety of a shorter DAPT duration. In patients with stable angina who have PCI, especially those at high bleeding risk, the totality of data demonstrate the safety and efficacy of 1-month DAPT compared with longer durations, whether 3 months, 6 months or 12 months.
In the non-STEMI population, there are some data demonstrating the feasibility of discontinuing DAPT in favor of ticagrelor alone after only 1 month.
The only group of patients for whom the jury is still out are those who present with STEMI, in whom the shorter DAPT durations have not yet demonstrated the safety in comparison to a 12-month duration.
The other caveat is that our guidelines still recommend 12 months of DAPT in any patient with an MI as long as they are able to tolerate it from a bleeding risk perspective, perhaps due to the atherosclerotic and thrombotic milieu that exists in those patients.
But certainly, for the majority of stable patients, 1-month DAPT appears to be adequate.
Having said this, each decision should be patient-specific, and there may be comorbid conditions, lesion characteristics or procedural details that make longer-term DAPT a better recommendation for some patients.
Krishnaswamy is section head of invasive & interventional cardiology in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute and the T.V. Connelly Family Chair in Interventional Cardiology at Cleveland Clinic.
References:
- Bhatt DL, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)31887-2.
- Bonaca MP, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1500857.
- CAPRIE Steering Committee. Lancet. 1996;doi:10.1016/S0140-6736(96)09457-3.
- Eikelboom JW, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1709118.
- Ge Z, et al. Lancet. 2024;doi:10.1016/S0140-6736(24)00473-2.
- Koo BK, et al. Lancet. 2021;doi:S0140-6736(21)01063-1.
- Mehran R, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1908419.
- Steg PG, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1908077.
- Yusuf S, et al. N Engl J Med. 2001;doi:10.1056/NEJMoa010746.
For more information:
Deepak L. Bhatt, MD, MPH, MBA, can be reached at deepak.bhatt@mountsinai.org; X (Twitter): @dlbhattmd.
Robert A. Harrington, MD, FAHA, MACC, FESC, can be reached on X (Twitter) at @heartbobh.
Amar Krishnaswamy, MD, can be reached at krishna2@ccf.org.
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