NOTA 1

The conditions in NOTA one were verified for both short-term and chronic users.

We firstly checked the following requirement

A. In the period starting from 180 days before the index date up to 31/12/2019, being prescribed with both low-dose ASA (ATC: B01AC06 N02BA01), and nonsteroidal anti-inflammatory drugs (NSAIDs - ATC: M01*) for at least 90 days each (also not consecutive).

In case condition A was not satisfied, we checked for

B. In the same period of assessment, being prescribed with or ASA or NSAIDs for at least 90 days.

In addition to condition B, at least one of the following conditions had to occur during the same period of assessment:

1. Being prescribed at least 90 days with corticosteroids (ATC: H02* or R01AD*) or other anticoagulants (ATC: B01*, excluded ASA and Vitamin K antagonists);

2. Having received two or more packages of Vitamin K antagonists;

3. Being aged 75 years or more (Franchi et al., 2020);

or within 24 months before the index date:

4. Being discharged from hospital with a diagnosis of Helicobacter Pylori (HP) infection or of peptic ulcer or hemorrhages of esophagus, stomach, or duodenum (ICD-9-CM codes in Supplementary Table S1);

5. Undergoing to diagnostic tests to ascertain the presence of peptic ulcer, GERD or HP infection (ICD-9-CM codes in Supplementary Table S1).

For patients with index date from 01/10/2019 to 31/12/2019, the prescription with drugs mentioned above (e.g. ASA, NSAID etc.) except those for GERD was assessed up to 31/03/2019, in order to avoid bias due to different time exposures.

A diagnosis of specific chronic conditions that may entail a long-term treatment with NSAIDs was considered as an alternative of having prescriptions with NSAIDs both in condition A and B (Supplementary Table S1).