Meta-analysis Supports Benefits of Short-term DAPT Among Elderly Patients
Excluded from the major DAPT trials, elderly patients remain one of the more difficult subgroups in which to balance bleeding and ischemic risks.
A new meta-analysis is helping to fill a knowledge gap regarding the optimal duration of dual antiplatelet therapy (DAPT) in elderly patients treated with drug-eluting stents, supporting a less-is-more approach.
“The main clinical message is that short-term DAPT may be considered in elderly patients receiving next-generation DES to reduce bleeding events without an increase of ischemic events,” study co-author Myeong-Ki Hong, MD (Yonsei University Health System, Gunpo, Korea), told TCTMD in an email, adding that he would like to see future randomized trials look at this issue.
DAPT duration has been debated for a wide variety of patients since the publication of both the DAPT and PEGASUS-TIMI 54 trials, but elderly individuals have typically been underrepresented in randomized trials that investigated different DAPT durations following DES implantation, write the study authors led by Seung-Yul Lee, MD (Wonkwang University College of Medicine, Gunpo, Korea).
Published online ahead of print in JACC: Cardiovascular Interventions, the meta-analysis included six randomized trials—RESET, EXCELLENT, PRODIGY, OPTIMIZE, SECURITY, and ITALIC—involving 11,473 patients assigned to short-term (3 or 6 months) or long-term (12 or 24 months) DAPT. Just over half of the population (53.6%) were younger than 65 years old, and the rest were considered elderly. Almost all patients (89.6%) received newer-generation DES.
Overall, there was no difference in the risk of the primary composite endpoint (MI, definite/probable stent thrombosis, or stroke at 12 months) between patients who received short- versus long-term DAPT (unadjusted HR 1.12; 95% CI 0.88-1.43). However, the researchers observed a significant interaction between age and DAPT duration with regard to the primary endpoint (P for interaction = 0.0384).
In younger patients, the risk of the primary endpoint was higher in patients on short-duration DAPT after adjustment for baseline characteristics (adjusted HR 1.67; 95% CI 1.14-2.44), and this was mainly driven by a higher risk of MI (adjusted HR 1.56; 95% CI 1.03-2.36). However, in the older patients, there was no difference in the risk of the primary endpoint between those on short versus long DAPT even after adjustment (adjusted HR 0.84; 95% CI 0.60-1.16).
In terms of safety, short versus long DAPT was associated with a reduced risk of major bleeding (unadjusted HR 0.50; 95% CI 0.30-0.84). This relationship was not evident in younger patients, but it was clearly observed in the elderly cohort (unadjusted HR 0.46; 95% CI 0.24-0.88).
“Short-term DAPT after next-generation DES implantation, compared with long-term DAPT, may be more beneficial in elderly patients than in younger patients,” the authors conclude. “New-generation DES requiring a duration of DAPT that is shorter than 3 months (eg, 1 month) might be considered as an alternative option in the treatment of elderly patients.”
Commenting on the study for TCTMD, Robert Yeh, MD (Beth Israel Deaconess Medical Center, Boston, MA), called the findings "consistent with an emerging picture."
Elderly patients, he told TCTMD in an email, "may be particularly susceptible to the bleeding-related harms of more prolonged or more potent antithrombotic therapy. Certainly this is what we observed in the DAPT study, where we observed that the risk-benefit profile became more and more in favor of shorter duration therapy with advancing age."
Indeed, in the DAPT Score, derived from the trial, increasing age is the only factor that lowers a patient's score, he noted.
Several studies are underway that may provide more answers, Yeh added. "Short duration DAPT studies such as EVOLVE-Short DAPT and Xience 90 both include elderly age as one of the defining characteristics of high bleeding risk," he said. "Understanding the safety of shorter durations in this population will really help us to potentially avoid iatrogenic harm related to DAPT-related bleeding."
Note: Senior study author Gregg W. Stone, MD, is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.
Lee S-Y, Hong M-K, Palmerini T, et al. Short-term versus long-term dual antiplatelet therapy after drug-eluting stent implantation in elderly patients: a meta-analysis of individual participant data from six randomized trials. J Am Coll Cardiol Intv. 2018;Epub ahead of print.
- The study was supported by a grant from the Korea Healthcare Technology Research & Development Project, Ministry for Health & Welfare, Republic of Korea, the Mid-Career Researcher Program through an NRF grant funded by the MEST, Republic of Korea, and the Cardiovascular Research Center, Seoul, Korea.
- Hong and Lee report no relevant conflicts of interest.
- Yeh reports holding an investigator-initiated research grant funded by AstraZeneca.