Table 2. Summary of studies examining cardiovascular adverse events in gastroesophageal reflux disease patients using proton pump inhibitors.

PPI- proton pump inhibitors; RCT- randomized controlled trial; GERD- gastroesophageal reflux disease; SOPRAN- Safety of Omeprazole in Peptic Reflux Esophagitis: A Nordic Open Study; LOTUS- Long Term Usage of Esomeprazole vs. Surgery for Treatment of chronic GERD; TIA- transient ischemic attack; MI- myocardial infarction; CV event- cardiovascular event

Study (year)	Design	Total patients (patients taking PPIs)	Patient condition	PPI assigned	Comments
Casula et al. (2018) [23]	Nested case-control study	Control (89,160), Cases (17,832)	New PPI users	any PPI	The risk of a new-onset cardiovascular event was higher in current and recent users
Xie et al. (2017) [24]	Observational cohort study	1,762,908 (275,977)	New PPI users	any PPI	Current and past use of PPIs was associated with increased risk of death
Attwood et al. (2015) [25]	Open-label RCT	SOPRAN: 298 (154), LOTUS: 514 (266)	GERD	SOPRAN: Omeprazole, LOTUS: Esomeprazole	Omeprazole group: CV events- 28, TIA events- 3, Esomeprazole group: MI events- 5, angina events- 3
Lundell et al. (2009) [26]	RCT	310 (154)	GERD	Omeprazole	PPI group: death due to heart complications- 8, Non-fatal MI event- 9
Lundell et al. (2008) [27]	RCT	554 (266)	GERD	Esomeprazole	CV event- 3 in the PPI group; CV event- 4 in the surgery group