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UTILIZATION OF PROTON PUMP INHIBITORS IN PATIENTS WITH OVERT GASTROINTESTINAL BLEEDING: EFFECTS ON SHORT- AND LONG-TERM MORTALITY AND REBLEEDING

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Introduction

Proton pump inhibitors (PPI) may be over or underutilized in patients with acute gastrointestinal bleeding (AGIB). Further, the effects of their use on short- and long-term outcomes are not clear.

Aims & Methods

We examined utilization of PPI in patients with AGIB and its effect on short- and long-term rebleeding and mortality in a prospective study of patients admitted with AGIB to a tertiary referral center between Jan. 2013 and Aug. 2023. We determined intake of PPI on admission and on discharge, and intake of antithrombotics [antiplatelets (AP) only, anticoagulants (AC) only or both AP and AC] on admission and on discharge. Univariate analysis was done to compare patients using PPI on admission or on discharge to patients not using PPI. Multivariate analysis was done to determine independent predictors of mortality and rebleeding.

Results

846 patients with AGIB (462 had upper GIB) were admitted and followed-up for a median of 59 (29-88) months. 385 were admitted already taking PPI. 623 patients were discharged on PPI and 150 were discharged off PPI (73 patients died in hospital). 49% of patients admitted on PPI and 27% of patients discharged on PPI did not have a clear indication for their use. The overall PPI overutilization rate was 36%. 25% of patients discharged off PPI had at least one clear indication for their use.
Compared to patients admitted off PPI, those admitted on PPI were older (66 vs 70 years, p<0.001), had higher Charlson Comorbidity Index (CCI) (2.4 vs 3.2, p<0.001), were more likely to be on antithrombotics (56% vs 70%, p<0.001) and to require blood transfusion (54% vs 64%, p=0.003). They also had higher 1-month mortality (8% vs 16%, p<0.001). However, they had less stigmata of recent hemorrhage (SRH) (39% vs 30%, p=0.022) and were less likely to require endoscopic therapy (25% vs 15%, p=0.002). Compared to patients discharged off PPI, patients discharged on PPI were more likely to have had in-hospital re-bleeding (1.3% vs 5.3%, p=0.036) but had similar short- and long-term mortality (4.7% vs 2.9%, p= 0.301 and 37% vs 44%, p=0.122, respectively).
On multivariate analysis, PPI on admission was not an independent predictor of 1-month mortality or re-bleeding [OR 1.46 (0.83, 2.57), p= 0.187 and 0.91 (0.51, 1.59), p=0.730], respectively. Predictors of 1-month mortality were CCI [OR 1.13 (1.04,1.22), p=0.002], severe bleeding [OR 2.48 (1.21, 5.10), p=0.013], blood transfusion [OR 2.72 (1.20, 6.15), p=0.017], and SRH [OR 2.53 (1.40, 4.59), p=0.002]. Predictors of 1-month re-bleeding were AC only on admission [OR 2.30 (1.20, 4.42), p= 0.012], severe bleeding [OR 1.96 (1.03, 3.73), p=0.041], and SRH [OR 2.03 (1.16, 3.54), p=0.013]. PPI on discharge was not a predictor of long-term mortality or re-bleeding (table 1). Being on AC only on discharge was a predictor of long-term mortality, while being on AP only on discharge was protective against long-term re-bleeding (table 1).

	Variables	OR (95% CI)	p-value		Variables	OR (95% CI)	p-value
Long-term Mortality**	PPI on discharge	1.38 (0.85, 2.26)	0.194	Long-term Re-bleeding**	PPI on discharge	1.26 (0.76, 2.07)	0.375
	Age-related CCI	1.53 (1.41, 1.67)	<0.001		AP only on discharge	0.45 (0.28, 0.72)	0.001
	Blood transfusion	1.72 (1.18, 2.51)	0.005		AC only on discharge	0.91 (0.54, 1.56)	0.741
	AP only on discharge	0.85 (0.55, 1.32)	0.479		AP and AC on discharge	0.56 (0.29, 1.10)	0.095
	AC only on discharge	2.51 (1.45, 4.36)	0.001		Severe bleeding*	1.53 (1.03, 2.25)	0.034
	AP and AC on discharge	0.91 (0.50, 1.7)	0.749		SRH	1.78 (1.21, 2.64)	0.004
Table 1: Multivariate analysis showing predictors of long-term mortality and re-bleeding in patients with acute GIB. AP: antiplatelets; AC: anticoagulants; Hb: Hemoglobin level; CCI: Charlson Comorbidity Index; Severe bleeding is defined as: Hb drop ≥ 2 units, blood transfusions ≥ 2 units, or systolic blood pressure on admission ≤ 100 mmHg. * long term mortality and re-bleeding are defined as mortality or re-bleeding by the end of follow-up.

Conclusion

There is marked overutilization and underutilization of PPI in patients with GIB, without a significant effect on short- or long-term mortality or rebleeding. A PPI utilization stewardship program is needed to decrease health care costs and potential PPI related side effects.