Original Investigation
Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy

https://doi.org/10.1016/j.jacc.2022.04.065Get rights and content
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Abstract

Background

Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials.

Objectives

The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial.

Methods

At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3.

Results

In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation.

Conclusions

In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)

Key Words

acetylsalicylic acid
drug-eluting stent
dual antiplatelet therapy
high bleeding risk
P2Y12 inhibitor

Abbreviations and Acronyms

DAPT
dual antiplatelet therapy
IPCW
Inverse probability-of-censoring weights
ITT
intention-to-treat
MACE
major adverse cardiac and cerebral events
MCB
major or clinically relevant nonmajor bleeding
NACE
net adverse clinical events
NARC
nonadherence Academic Research Consortium
OAC
oral anticoagulation
SAPT
single antiplatelet therapy

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Listen to this manuscript's audio summary by Editor-in-Chief Dr Valentin Fuster on www.jacc.org/journal/jacc.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

A complete list of the MASTER DAPT investigators is provided in the Supplemental Appendix.