Associations Between Antihypertensive Medications and Severe Hyponatremia: A Swedish Population–Based Case–Control Study

• Published in: The journal of clinical endocrinology and metabolism 2020-10, Vol.105 (10), p.e3696-e3705
• Main Authors: Falhammar, Henrik, Skov, Jakob, Calissendorff, Jan, Nathanson, David, Lindh, Jonatan D, Mannheimer, Buster
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin; Angiotensin II; Angiotensin-converting enzyme inhibitors; Antihypertensive Agents - adverse effects; Antihypertensive drugs; Antihypertensives; Calcium; Care and treatment; Case-Control Studies; Causes of; Complications and side effects; Diuretics; Drug Prescriptions - statistics & numerical data; Endokrinologi och diabetes; Farmakologi och toxikologi; Female; Hospital care; Hospitalization; Hospitalization - statistics & numerical data; Humans; Hypertension - drug therapy; Hyponatremia; Hyponatremia - chemically induced; Hyponatremia - epidemiology; Klinisk medicin; Male; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Online Only; Peptidyl-dipeptidase A; Population studies; Population-based studies; Registries - statistics & numerical data; Retrospective Studies; Socioeconomic factors; Sweden - epidemiology; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa194

Abstract Background Calcium channel blockers (CCBs), beta-receptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs) have occasionally been reported to cause severe hyponatremia. The aim was to explore the association between CCBs, BBs, ACEIs, and ARBs and hospitalization due to hyponatremia. Methods Patients hospitalized with a principal diagnosis of hyponatremia (n = 11 213) were compared with matched controls (n = 44 801). Linkage of national population-based registers was used to acquire data. Multivariable logistic regression adjusting for co-medications, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between hospitalization for severe hyponatremia and the use of different CCBs, BBs, ACEIs, and ARBs. Furthermore, newly initiated (≤90 days) and ongoing use were examined separately. Results Adjusted odds ratios (aORs) (95% confidence interval) for the investigated 4 drug classes ranged from 0.86 (0.81-0.92) for CCBs to 1.15 (1.07-1.23) for ARBs. For newly initiated drugs, aORs spanned from 1.64 (1.35-1.98) for CCBs to 2.24 (1.87-2.68) for ACEIs. In contrast, the corresponding associations for ongoing therapy were not elevated, ranging from 0.81 (0.75-0.86) for CCBs to 1.08 (1.00-1.16) for ARBs. In the CCBs subgroups, aOR for newly initiated vascular CCBs was 1.95 (1.62-2.34) whereas aOR for ongoing treatment was 0.82 (0.77-0.88). Conclusions For newly initiated CCBs, BBs, ACEIs, and ARBs, the risk of hospitalization due to hyponatremia was moderately elevated. In contrast, there was no evidence that ongoing treatment with investigated antihypertensive drugs increased the risk for hospitalization due to hyponatremia.