Table 7.

Key studies establishing the link between AST and adverse cardiovascular outcomes

Study	Study characteristic	Key findings
Charlot et al.110	Nationwide cohort study N = 56,406 adults hospitalized for MI	PPI use was associated with an increased risk of adverse cardiovascular outcomes after discharge for MI, independent of clopidogrel use
Shah et al.111	Data mining studies N = 2.9 million individuals	PPI users had a 1.16-fold increased risk of MI with a two-fold increase in cardiovascular mortality On the contrary, the use of H2RAs was not associated with an increased cardiovascular risk
Sehested et al.112	Nationwide registry-based analysis N = 2,14,998 patients post upper gastrointestinal endoscopy	PPIs may be associated with an increased risk of first-time ischemic stroke (HR, 1.13; p < 0.001) and MI (HR, 1.31; p < 0.001), with greater risk among long-term users and at high doses H2RA use was not significantly associated with ischemic stroke (HR, 1.02) or MI (HR, 1.15)
Shiraev et al.113	A systematic review of 27 studies N = 22,427 patients in cardiovascular mortality datasets and N = 3,54,446 patients in morbidity datasets	PPI use significantly increased the risk of all-cause mortality (OR, 1.68, p < 0.001) and rate of major cardiovascular events (OR, 1.54, p = 0.01)
Bell et al.114	Cohort study N = 6,538	Individuals with a cumulative PPI exposure exceeding 5.1 years showed a 2.02-fold higher risk of CVD and 2.21-fold higher risk of HF compared with nonusers
Genge et al.115	N = 19,229 adults with T2DM	PPI use was significantly associated with higher risks of CAD (HR, 1.27), MI (HR, 1.34), HF (HR, 1.35), and all-cause mortality (HR, 1.30)

CAD, coronary artery disease; HF, heart failure; MI, myocardial infarction; T2DM, type 2 diabetes mellitus