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. 2022 Jun;31(6):670-679.
doi: 10.1002/pds.5428. Epub 2022 Mar 24.

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis

Magdalene M Assimon  1 , Patrick H Pun  2   3 , Sana M Al-Khatib  3   4 , M Alan Brookhart  5 , Bradley N Gaynes  6   7 , Wolfgang C Winkelmayer  8 , Jennifer E Flythe  1   9
Affiliations

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis

Magdalene M Assimon et al. Pharmacoepidemiol Drug Saf. 2022 Jun.

Abstract

Purpose: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions.

Methods: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]).

Conclusions: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Keywords: USRDS; citalopram; escitalopram; hemodialysis; proton pump inhibitor; sudden cardiac death.

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Figures

Figure 1.
Figure 1.. Study design
We determined if citalopram, escitalopram, and sertraline new-users were or were not using a PPI at the time of SSRI initiation by determining if they filled a prescription for a PPI that overlapped the index date. Abbreviations: PPI, proton pump inhibitor; SSRI, selective serotonin reuptake inhibitor; Rx, prescription.
Figure 2.
Figure 2.. Flow diagram depicting study cohort assembly
a To be included in the study, patients had to receive in-center hemodialysis during the 180-days prior to study medication initiation (i.e., the baseline period) and also have continuous Medicare Part A, B, and D coverage during this period. Abbreviations: PPI, proton pump inhibitor.
Figure 3.
Figure 3.. Association between SSRI–PPI exposure status and the 1-year risk of sudden cardiac death
An on-treatment analytic approach was used in all analyses. Fine and Gray proportional subdistribution hazards models were used to estimate hazard ratios, and inverse probability of treatment weighting was used for confounding control. Abbreviations: CI, confidence interval; cital/escital, citalopram or escitalopram; HR hazard ratio; PPI, proton pump inhibitor; ref., referent; sert, sertraline.
Figure 4.
Figure 4.. Association between SSRI–PPI exposure status and the 1-year risk of sudden cardiac death considering citalopram and escitalopram separately
An on-treatment analytic approach was used in all analyses. Fine and Gray proportional subdistribution hazards models were used to estimate hazard ratios, and inverse probability of treatment weighting was used for confounding control. Abbreviations: CI, confidence interval; cital, citalopram; escital, escitalopram; HR hazard ratio; PPI, proton pump inhibitor; ref., referent; sert, sertraline.
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