1. DAPT Mortality and Cancer: Focus on HIRA Database
Korean Outcomes Registry
Evaluating Antithrombotics (KOREA)
Victor Serebruany, MD, PhD
Owner, HeartDrug™ Research LLC;
Johns Hopkins University;
Busan, December 9, 2016

2. Why the Topic is So Hot ? Conflicting Results of Clinical Trials
Conflicting FDA Reviews
Extreme clinical importance

3. DAPT Trial Cancers

4. Confusion over DAPT results
Before AHA
After AHA

5. All New Solid Cancers After 7 Days in TRITON
months
0, , , , ,020
Fraction of Subjects
Number at risk
rx=Clopidogrel
rx=Prasugrel
rx=Clopidogrel rx=Prasugrel
The FDA Secondary Prasugrel Review, 2009

6. Meta-Analysis of Solid Cancers in the Thienopyridine Invasive Trials for Which the FDA Has Cancer Data

7. Hazard Ratio=2.5 (95% CI 1.4-4.6; p=0.002)
Solid Cancers in APPRAISE
Hazard Ratio=2.5 (95% CI ; p=0.002)

8. Times to First Solid Cancer Events by Arm in TRACER
FDA Secondary Vorapaxar Review, 2014

9. Times to First Solid Cancer Events by Arm in TRA2P
FDA Secondary Vorapaxar Review, 2014

10. Follow-up Rates in Patients with and without GUSTO Moderate/Severe Bleeding Events in TRA2P
FDA Secondary Vorapaxar Review, 2014

11. HIRA Database:
The Health Insurance Review and Assessment (HIRA) service receives the claims of 97% of the population in South Korea;
In 2010, the number of beneficiaries was 48,906,795 among the entire population (50,515,666) of the country;
Accordingly, the HIRA database contains information on almost all insurance claims for the entire country, including prescribed medications, procedures, and outcomes.

12. POPULATION:
HIRA post-PCI claims (June July 2013) ; Age >18 years
Inclusion: DAPT with aspirin and clopidogrel (517900ACH) for
1 year, and then either DAPT, or monotherapy with aspirin
(N02BA01; B01AC06) for extra 18 months.
Exclusions:
History of PCI prior to 2009,
Repeated PCI ( ) over the follow-up,
Not verifiable vital status,
Unknown DAPT or ASA duration,
Acute myocardial infarction (I21.X),
Stroke (I63.X),
Bleeding (H11.3, H.43.1,H45.0, I60.X, I62X, K22.6, K25-28.X, K28.7),
Any cancer (C00.X–C96.X) occurring within one year since PCI.

13. Study Flow Chart:

14. Major Findings Outcome DAPT (n=32,539) DAPT-C (n=10,992) ASA
P-value
All Deaths
Any Cancer
462 (1.42%)
1,433 (4.40%)
136 (1.24%)
455 (4.15%)
192 (1.28%)
606 (4.04%)
0.99
0.005

15. Impressions:
HIRA/KOREA data reveal a mild excess of cancer risk, but no mortality benefit in Korean post-PCI patients treated with DAPT for an additional 18 months beyond conventional 12 months DAPT.
These data challenge continuing DAPT for more than 1 year in East Asians.
Future: cancer types and potential cancer association with bleeding and newer
antiplatelet agents are warranted.