Impact of age on comparative outcomes of abbreviated versus standard antiplatelet therapy in patients at high bleeding risk: a pre-specified analysis from the MASTER-DAPT trial
A Landi, A Zito, Y Ozaki, M C Morice, A E Rodriguez, A Milzi, A Moschovitis, P Laanmets, M Donahue, S Leonardi, E Frigoli, P C Smits, M ValgimigliAbstract
Background
Dual antiplatelet therapy (APT) with aspirin and a P2Y12 inhibitor is the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the risk of ischemic complications. Abbreviated dual APT reduces bleeding with no increase in ischemic events in high bleeding risk (HBR) patients undergoing PCI. The risk of ischemic and bleeding events after PCI increases with age. Yet, the comparative effectiveness of abbreviated versus standard APT in elderly patients at HBR remains unknown.
Purpose
To investigate the impact of age on the comparative effectiveness and safety of abbreviated versus standard DAPT in the largest contemporary cohort of HBR patients undergoing PCI.
Methods
In the multicenter, randomized, open-label MASTER DAPT trial, 4,579 HBR patients were randomized at 1 month after PCI to an abbreviated or standard APT. Coprimary outcomes were net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACCE), and major or clinically relevant non-major bleeding (BARC type 2, 3, or 5 bleeding) at 11 months after randomization. This pre-specified sub-study evaluates the outcomes of abbreviated versus standard DAPT according to patient age (≥ or < 75 years).
Results
Of the 4579 patients included, 3154 (68.9%) were ≥75 years of age. Elderly patients had a higher cardiovascular risk profile, including arterial hypertension, diabetes mellitus, prior MI or complex PCI compared with patients aged less than 75 years. At 11-month follow-up, NACE did not differ with abbreviated and standard APT among patients aged ≥75 years (hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.70-1.14) and < 75 years (HR: 1.06; 95% CI: 0.72-1.56, Pinteraction= 0.47) (Figure 1). Similarly, MACCE did not differ in patients aged ≥75 years (HR: 0.90; 95% CI: 0.68-1.19) and < 75 years (HR: 1.27; 95% CI:0.81- 1.99; Pinteraction= 0.21) (Figure 1). Abbreviated APT was associated with consistently lower BARC 2,3 or 5 bleeding in patients aged ≥75 years (HR: 0.66; 95% CI: 0.51-0.84) and <75 years (HR: 0.76; 95% CI: 0.51-1.15; Pinteraction=0.53) (Figure 2).Cubic splines showed that the absolute risk reduction in bleeding with abbreviated APT progressively increased as a function of age. The rate of myocardial infarction was numerically higher with abbreviated versus standard APT in younger (2.7% vs 1.4%), but not in elderly patients (2.6% vs 2.5%).
Conclusions
Among HBR patients undergoing PCI, abbreviated APT was associated with comparable rates of NACE and MACCE and significantly reduced bleeding irrespective of age. These findings support an abbreviated APT regimen in HBR patients undergoing PCI, particularly in elderly patients who may derive greater bleeding benefit without increased ischemic risk compared with younger patients.Figure 1Figure 2