Gout
Aiya Almogaber, PharmD
Patients with gout who were given NSAIDs to prevent flare-ups when starting allopurinol faced a higher risk of serious heart problems than those given colchicine or no preventive medication, said a study in Arthritis & Rheumatology from May 26, 2025.
The research provides rare head-to-head safety data on two widely used strategies for managing gout flares during urate-lowering therapy.
Gout is a common inflammatory arthritis affecting more than 5% of U.S. adults and is strongly associated with cardiometabolic comorbidities. Patients face increased risks of premature mortality, particularly from CVD. To help patients tolerate urate-lowering therapy, such as allopurinol, physicians often prescribe a short course of colchicine or NSAIDs to prevent flare-ups in the first few months. Both options are recommended in clinical guidelines, but until now, there has been little direct evidence comparing their safety in real-world patients with gout.
The study included more than 18,000 matched patients, most of them men with an average age of 61. Patients who received NSAIDs experienced more cardiovascular problems than those given colchicine, with major adverse events occurring at a rate of about 90 per 1,000 person-years compared with 55 per 1,000 in the colchicine group. NSAID users were also more than twice as likely to die from cardiovascular causes.
When NSAID use was compared to starting allopurinol without any preventive therapy, the increased risk persisted. Patients taking NSAIDs had a 50% higher risk of major cardiovascular events and nearly double the risk of heart attack. In contrast, colchicine use did not raise cardiovascular risk compared with no preventive treatment.
These findings were consistent across additional analyses that shortened follow-up time and applied different statistical methods, and the higher risk linked to NSAIDs was especially pronounced in patients treated after 2013, when gout guidelines first began recommending preventive therapy.
Study design and population
Researchers used health data covering nearly all residents of British Columbia, Canada. They focused on adults who started allopurinol between 1995 and 2022 and received either colchicine or an NSAID on the same day. Patients who had used allopurinol in the prior 6 months or had recently taken colchicine, NSAIDs (including aspirin), or steroids were excluded in order to ensure the drugs were being used for new flare prevention.
The primary outcome was the incidence of major adverse cardiovascular events, defined as a composite of myocardial infarction, stroke, or cardiovascular death. Secondary outcomes included individual cardiovascular events and all-cause mortality. Follow up extended until outcome occurrence, medication discontinuation or switch, deregistration, or end of the study period.
An important feature of the research was its “target trial emulation” design, which aimed to mirror the rigor of a randomized controlled trial while using observational data. By matching patients and comparing new users of each drug, the researchers were able to reduce bias and strengthen the reliability of their findings. The size of the dataset, which included the entire provincial population, also gave the study broad real-world relevance.
Implications for patient care
Both NSAIDs and colchicine remain guideline-approved choices for preventing flares when patients begin urate-lowering therapy. But the new evidence suggests the two drugs are not equally safe. In a patient group already at high risk for heart problems, colchicine stood out as the option without added cardiovascular risk.
The results may influence how physicians discuss treatment options with patients starting allopurinol.
While some patients cannot tolerate colchicine or may have contraindications, this study underscores the importance of weighing the potential heart risks when considering NSAIDs for gout flare prevention.
The authors noted that their findings add important context to earlier research showing general cardiovascular risks of NSAIDs but with the addition of a unique comparison within a gout-specific population. By directly contrasting NSAIDs and colchicine, the study findings help clarify which option may be safer for patients who already face heavy cardiovascular burdens. ■