Ischaemic cardiovascular risk with allopurinol and protective effect of colchicine in gout: a Dutch nationwide pharmaco-epidemiological study

TY - JOUR

T1 - Ischaemic cardiovascular risk with allopurinol and protective effect of colchicine in gout

T2 - a Dutch nationwide pharmaco-epidemiological study

AU - Peeters, Iris Rose

AU - Wientjes, Maike H. M.

AU - Mackenzie, Isla S.

AU - Opdam, Merel A. A.

AU - Flendrie, Marcel

AU - Popa, Calin D.

AU - van de Wiel, Kayleigh M.

AU - Vojinovic, Dina

AU - Joosten, Leo A. B.

AU - Schouwenberg, Bas

AU - Gerritsen, Martijn

AU - den Broeder, Alfons A.

AU - van Herwaarden, Noortje

N1 - Copyright: © The Author(s) 2025.

PY - 2026/3

Y1 - 2026/3

N2 - Aims: Gout is associated with increased ischaemic cardiovascular disease (CVD). The effects of allopurinol and colchicine on CVD risk remain debated. This study aims to investigate the interplay between these factors. Methods and results: This was a pharmaco-epidemiological study, including adult gout patients prescribed allopurinol between October 2015 and December 2022. Cardiovascular disease was operationalized as a new prescription for a platelet aggregation inhibitor. Incidence densities (CVD/100 patient-years) were compared using incidence rate ratios (IRRs). Time periods based on allopurinol use were defined: (i) before initiation, (ii) first 30 days after initiation, (iii) continued use, (iv) first 30 days after discontinuation, and (v) prolonged discontinuation. Effect modification by initial allopurinol dose—low (<300 mg) or high (≥300 mg)—and concomitant colchicine use were assessed. Included were 84,582 patients [77% male, mean age 66 years (standard deviation 13.4)], with 122 659 treatment episodes and 13 568 CVD events. Cardiovascular disease IRRs for Periods 2–5 (reference Period 1) were: 1.51 [95% confidence interval (CI) 1.29–1.77], 1.07 (95% CI 1.03–1.12), 1.20 (95% CI 1.02–1.43), and 0.94 (95% CI 0.88–1.00), respectively. The increased CVD risk after allopurinol initiation was dose-dependent (IRR: low dose 1.69; 95% CI 1.31–2.18; high dose 3.92; 95% CI 2.73–5.63). Concomitant colchicine use attenuated this risk: IRR 1.02 (95% CI 0.78–1.32) for low-dose and 1.18 (95% CI 0.65–2.16) for high-dose allopurinol. Conclusion: Allopurinol initiation was associated with a substantial and dose-dependent increase in CVD risk in gout patients, especially in the first 30–90 days and at dosages ≥300 mg/day. Concomitant colchicine use reduced this risk. Discontinuation of allopurinol was not associated with CVD risk.

AB - Aims: Gout is associated with increased ischaemic cardiovascular disease (CVD). The effects of allopurinol and colchicine on CVD risk remain debated. This study aims to investigate the interplay between these factors. Methods and results: This was a pharmaco-epidemiological study, including adult gout patients prescribed allopurinol between October 2015 and December 2022. Cardiovascular disease was operationalized as a new prescription for a platelet aggregation inhibitor. Incidence densities (CVD/100 patient-years) were compared using incidence rate ratios (IRRs). Time periods based on allopurinol use were defined: (i) before initiation, (ii) first 30 days after initiation, (iii) continued use, (iv) first 30 days after discontinuation, and (v) prolonged discontinuation. Effect modification by initial allopurinol dose—low (<300 mg) or high (≥300 mg)—and concomitant colchicine use were assessed. Included were 84,582 patients [77% male, mean age 66 years (standard deviation 13.4)], with 122 659 treatment episodes and 13 568 CVD events. Cardiovascular disease IRRs for Periods 2–5 (reference Period 1) were: 1.51 [95% confidence interval (CI) 1.29–1.77], 1.07 (95% CI 1.03–1.12), 1.20 (95% CI 1.02–1.43), and 0.94 (95% CI 0.88–1.00), respectively. The increased CVD risk after allopurinol initiation was dose-dependent (IRR: low dose 1.69; 95% CI 1.31–2.18; high dose 3.92; 95% CI 2.73–5.63). Concomitant colchicine use attenuated this risk: IRR 1.02 (95% CI 0.78–1.32) for low-dose and 1.18 (95% CI 0.65–2.16) for high-dose allopurinol. Conclusion: Allopurinol initiation was associated with a substantial and dose-dependent increase in CVD risk in gout patients, especially in the first 30–90 days and at dosages ≥300 mg/day. Concomitant colchicine use reduced this risk. Discontinuation of allopurinol was not associated with CVD risk.

KW - Gout

KW - Allopurinol

KW - Cardiovascular disease risk

KW - Colchicine prophylaxis

UR - https://www.scopus.com/pages/publications/105039393493

U2 - 10.1093/eurjpc/zwaf513

DO - 10.1093/eurjpc/zwaf513

M3 - Article

C2 - 40799125

SN - 2047-4873

VL - 33

SP - 682

EP - 690

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

IS - 5

ER -