Key result
Losartan combined with amlodipine was the only ARB associated with a reduced risk of new-onset gout, while all ARBs similarly reduced major cardiovascular events.
Why the study?
Losartan uniquely inhibits URAT1 to exert a uricosuric effect unlike valsartan, telmisartan, and olmesartan, but whether this translates into clinically meaningful differences in gout risk and cardiovascular outcomes in amlodipine-based combination therapy had not been addressed in large-scale comparative studies.
Does the specific type of angiotensin receptor blocker (losartan, valsartan, telmisartan, or olmesartan) in amlodipine-based combination therapy reduce the risk of new-onset gout and major adverse cardiovascular events in patients with newly diagnosed hypertension?
Cohort (n=128,779)
Yes
Does the specific type of angiotensin receptor blocker (losartan, valsartan, telmisartan, or olmesartan) in amlodipine-based combination therapy reduce the risk of new-onset gout and major adverse cardiovascular events in patients with newly diagnosed hypertension?
Answers are grounded in this paper and cite their sources.
In newly diagnosed hypertensive patients on amlodipine/ARB therapy, losartan uniquely reduces the risk of incident gout while providing comparable MACE reduction to other ARBs.
Background Current hypertension guidelines recommend a calcium channel blocker/angiotensin receptor blocker (ARB) single-pill combination as first-line therapy. Among ARBs, losartan uniquely inhibits the urate transporter URAT1 in the proximal tubule, exerting a uricosuric effect, whereas valsartan, telmisartan, and olmesartan lack this property. Whether this pharmacological distinction translates into clinically meaningful differences in gout risk and subsequent cardiovascular outcomes has not been addressed in large-scale comparative studies. Purpose To compare the risk of new-onset gout and major adverse cardiovascular events (MACE) among four ARB types (losartan, valsartan, telmisartan, and olmesartan) when combined with amlodipine in newly diagnosed hypertension patients. Methods Using the Korean National Health Insurance Service database, we identified 397,913 patients newly diagnosed with hypertension without prior cardiovascular disease who received amlodipine/ARB combination therapy between 2010 and 2013. After applying exclusion criteria (history of gout, gout or MACE within 6 months, treatment switchers, non-study ARB users, and no health checkup records), 128,779 patients persisting on their initial regimen for ≥6 months were included. Non-persistent users served as controls. The primary outcome was new-onset gout; the secondary outcome was MACE (composite of cardiac death, myocardial infarction, and stroke). Inverse probability of treatment weighting (IPTW) was applied with a 1:1:1:1:1 ratio to balance baseline characteristics. Cox regression estimated hazard ratios (HRs) with 95% confidence intervals (CIs) over 5 years. Results Before IPTW, the study population consisted of 30,423 controls, 35,588 losartan, 23,033 valsartan, 25,441 telmisartan, and 14,294 olmesartan users. After 1:1:1:1:1 IPTW, the matched population comprised approximately 126,000 per group with well-balanced covariates (all standardised mean differences <0.1). For the primary outcome, losartan was the only ARB associated with a lower risk of new-onset gout (HR 0.904, 95% CI 0.877–0.932), whereas olmesartan (HR 1.101, 95% CI 1.069–1.133) and telmisartan (HR 1.041, 95% CI 1.010–1.072) showed higher risks; valsartan showed no significant difference (HR 1.015, 95% CI 0.985–1.045). For the secondary outcome, all four ARBs significantly reduced MACE versus control (HRs 0.573–0.584, all P<0.001). Among patients who developed gout, continued ARB use was associated with 21–37% lower MACE risk (olmesartan: HR 0.631; losartan: HR 0.679; telmisartan: HR 0.772; valsartan: HR 0.788). Conclusions In amlodipine-based first-line combination therapy, losartan was the only ARB associated with a reduced risk of new-onset gout, consistent with its uricosuric effect. All ARBs provided comparable MACE reduction. Losartan-based combination may offer additional benefit in mitigating gout risk among hypertensive patients.
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Bae et al. (2026) conducted a cohort in Newly diagnosed hypertension (n=128,779). Amlodipine combined with ARB (losartan, valsartan, telmisartan, or olmesartan) vs. Non-persistent users was evaluated on New-onset gout (HR 0.904, 95% CI 0.877-0.932). Losartan combined with amlodipine was the only ARB associated with a reduced risk of new-onset gout, while all ARBs similarly reduced major cardiovascular events.
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