Abstract: SA-PO903
Incident Thiazide Use and Outcomes in Advanced CKD: A Large Nationwide Observational Study of US Veterans
Session Information
- CKD: Clinical Trials and Pharmacoepidemiology
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials
Authors
- Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Shrestha, Prabin, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Mallisetty, Yamini, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Naser, Abu Mohd, The University of Memphis, Memphis, Tennessee, United States
- Surbhi, Satya, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Thomas, Fridtjof, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Streja, Elani, University of California Irvine, Irvine, California, United States
- Rhee, Connie, University of California Irvine, Irvine, California, United States
- Kalantar-Zadeh, Kamyar, University of California Irvine, Irvine, California, United States
- Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background
A recent randomized controlled trial showed that chlorthalidone therapy improved blood-pressure control in patients with advanced CKD and poorly controlled hypertension. It remains unclear if the use of thiazide diuretics improves clinical outcomes in patients with advanced CKD.
Methods
In a nationwide cohort of >3.5 million US veterans, we identified 266 patients with an eGFR <45 mL/min/1.73m2 who were incident new users of thiazides. Within the same 180-day calendar period, we identified 14,077 comparators who never used thiazides during the entire follow-up. After 1:1 propensity-score (PS) matching for socio-demographics, comorbidities, vital signs, eGFR, serum sodium and calcium, and relevant medications, the associations of thiazide use with incident ESKD and all-cause mortality were examined using competing risk regression and Cox regression models, respectively, overall and by subgroups of loop diuretic use status.
Results
Baseline characteristics were similar in patients with and without thiazide use (n=212 each) after PS matching. There were 54 and 184 cases of incident ESKD and all-cause death (event rates [95%CI], 35.3 [27.0-46.1] and 93.0 [80.5-107.5]/1000 PY) over a median follow-up of 3.0 and 4.2 years, respectively. Thiazide use was not associated with incident ESKD (sub-HR [95%CI], 0.94 [0.55-1.60]) nor with all-cause mortality (HR [95%CI], 0.99 [0.74-1.32]). There was a significant interaction between loop and thiazide diuretic use, with significantly higher thiazide-associated mortality risk observed in patients with loop diuretic use (1.67 [1.02-2.76]) (Table).
Conclusion
In patients with CKD stages G3b-G5, thiazide use was not significantly associated with incident ESKD or with all-cause mortality. The higher mortality risk associated with thiazide use in loop diuretic users may reflect an elevated risk of drug adverse effects and suggests the need for careful risk-benefit assessment for combination diuretic therapy in advanced CKD.
Associations of incident thiazide use (vs. no use) with outcomes in PS-matched cohort
| Incident ESKD | All-cause mortality | |||||||||
| SHR | 95% CI | P | P for interaction | HR | 95% CI | P | P for interaction | |||
| Overall | 0.94 | 0.55 | 1.60 | 0.82 | N/A | 0.99 | 0.74 | 1.32 | 0.93 | N/A |
| Subgroup | ||||||||||
| No loop diuretic use | 1.19 | 0.61 | 2.35 | 0.17 | 0.84 | 0.78 | 0.54 | 1.11 | 0.17 | 0.016 |
| Loop diuretic use | 0.95 | 0.23 | 4.00 | 0.95 | 1.67 | 1.02 | 2.76 | 0.043 | ||
Funding
- Veterans Affairs Support