Comparing Cardiovascular Outcomes Among Heated Tobacco Product Users, Cigarette Smokers, Former Smokers, and Never Smokers: Protocol for a Real-World Retrospective Study in Japan.

Abstract

Background: Smoking is a known risk factor for cardiovascular diseases (CVD). Despite widespread knowledge of the health risks of combustible cigarettes (CIG), many smokers continue to smoke. There have been efforts to provide alternatives, such as heated tobacco products (HTP), that may be less harmful than CIG.

Objective: To evaluate the impact of switching from CIG to HTP on the time to first subsequent major adverse cardiovascular event (MACE) compared with continued CIG smoking.

Methods: This retrospective cohort study will use health data from the Tokushukai Medical Database and tobacco exposure data from questionnaires and consumer databases in Japan. The study will include patients with a first cardiovascular event of non-fatal myocardial infarction (MI), unstable angina, or urgent coronary revascularization between May 2016 and December 2020 (Index Event); patients will be observed until March 2025. The primary exposure of interest is HTP use, while the primary comparator is continued CIG smoking pre- and post-index. The primary outcome is first post-index MACE (a composite outcome of any of the following: non-fatal MI, non-fatal stroke, hospitalization for angina, hospitalization for heart failure, urgent revascularization for angina, or all-cause mortality). After accounting for potential confounding factors with a propensity score weighting method, weighted log-rank tests and a weighted non-proportional Cox model will be used to compare the primary outcome between the exposure groups. Dual use of CIG and HTP, quitting CIG, and never smoking will also be analyzed as ancillary exposure groups to address secondary objectives.

Results: The study described in this protocol intends to assess whether there is a longer time to first MACE in HTP users as compared to CIG smokers.

Conclusions: This protocol describes a large-scale study that intends to identify patients with CVD from a nationally representative healthcare database and utilizes multiple data sources to evaluate their history of tobacco product usage. This will be the first study to assess the effect of HTP use on CVD outcomes by sex. Given the limited evidence on the health impacts of HTP in relation to CVD, the results of this study will provide insights into the effect of switching to HTP use compared to continued CIG smoking in patients with a prior cardiovascular event.