Certain Antihypertensive Drugs may Increase Risk of Hyperuricemia, Gout

Although different from most previous studies, results from a study published in Frontiers in Pharmacology¹ indicated that certain potassium-sparing diuretics, losartan, and calcium channel blockers may be associated with an increased risk of gout, hyperuricemia, and related adverse events (AEs), such as gouty arthritis, gouty tophus, and urate nephropathy. Additionally, certain antihypertensive drugs with central action, α and β blockers, vasodilators, and renin inhibitors, may also increase the risk of these conditions.

“The role of antihypertensive drugs in inducing hyperuricemia and gout has been a long-term concern in clinical practice,” Xue-Feng Jiao, an investigator associated with Sichuan University, and colleagues, stated. “However, clinical studies regarding this issue are limited in number and have yielded inconsistent results.”

Gout, a metabolic condition triggered by the deposit of monosodium urate crystals in the joints and the related soft tissues, and hyperuricemia, defined as elevated uric acid levels in the blood (above 7 mg/dL), are common comorbidities of hypertension. According to a National Health and Nutritional Examination Survey (NHANES), approximately three quarters (74%) of patients with gout have comorbid hypertension and a recent nationwide study in China observed a 38.7% rate of hyperuricemia in patients with hypertension.

Investigators determined the potential link between antihypertensive drugs and gout, hyperuricemia, and related AEs utilizing the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a spontaneous AE database. Data collected included demographics, administrative information, drug information, report sources, AEs, and patient outcomes. Their goal was to minimize risk by using real-world evidence to guide antihypertensive drug selection.

After disproportionality analyses, the numbers of antihypertensive drugs with positive signals for gout, hyperuricemia, gouty arthritis, gouty tophus, and urate nephropathy were 66, 46, 27, 8, and 6, respectively. These included antihypertensive drugs with central action, α blockers, β blockers, α and β blockers, diuretics, renin inhibitors and vasodilators. Calcium channel blockers, compound preparations, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers were also identified as positive signals for these AEs.

A positive signal for more than 1 AE was observed in a total of 42 antihypertensive drugs. All 5 AEs were determined as a positive signal in the drugs furosemide and amlodipine.

The large sample size provided by FAERS allowed investigators to identify rare adverse reactions. Further, a comprehensive assessment of the link between various antihypertensive drugs and hyperuricemia, gout, and related AEs was available as the study included both commonly used and less commonly used antihypertensive drugs. However, dosage information could not be evaluated given the limitations of the AE reports. Future research is needed to confirm findings and try to minimize the confounding effect of hypertension.

“These findings complement real-world evidence on the potential risks of hyperuricemia, gout and related AEs associated with antihypertensive drugs,” Jiao concluded. “According to our results, the recommendation of using losartan or calcium channel blockers for treatment of hypertension in patients with hyperuricemia or gout may not be appropriate.”

References

1. ^{Jiao XF, Song K, Jiao X, et al. Hyperuricaemia, gout and related adverse events associated with antihypertensive drugs: A real-world analysis using the FDA adverse event reporting system. Front Pharmacol. 2023;13:1045561. Published 2023 Jan 9. doi:10.3389/fphar.2022.1045561}