Gout is the most common type of inflammatory arthritis. It is associated with increased risks of heart attacks, strokes and higher mortality. Allopurinol is a very effective treatment that reduces significantly the frequency of long and painful flares in patients with gout. Several scientists believe that allopurinol could also reduce the elevated risks of heart attacks and strokes and increase survival in patients with gout. However, the randomized controlled trials reporting on the effects of allopurinol are imprecise and ambiguous.
On the other hand, some large observational studies reported reductions in heart attacks, strokes and mortality in patients using allopurinol. However, these studies had some methodological flaws in the way they were designed and analysed. These faults could have led to the apparent beneficial effects of allopurinol on these disease outcomes.
We propose to assess the effect of allopurinol on cardiovascular events and mortality in the CPRD, using a study design that avoids the methodological flaws found with the other studies.The results of this study will provide more accurate information to clinicians and patients on these potential additional major benefits of allopurinol for the treatment of gout.
Gout is the most common type of inflammatory arthritis. It is associated with increased risks of cardiovascular events and mortality. Allopurinol is highly effective at reducing urate levels and the frequency of flares in patients with gout, but it is unclear if it also reduces the risks of cardiovascular events and mortality. The randomized controlled trials and meta-analyses reporting on these outcomes with allopurinol are imprecise and ambiguous. On the other hand, large observational studies that reported major reductions in these outcomes with allopurinol were shown to be affected by time-related biases.
The objective of this study is to assess the effect of allopurinol use compared with non-use on the incidence of cardiovascular events and mortality in patients with gout, using the CPRD.
To avoid the time-related biases, we propose to use the prevalent new-user design, suitable in the absence of an active comparator, to compare the effect of new use of allopurinol with non-use on the incidence of cardiovascular events and mortality. We will first form, from CPRD practices, a base cohort of all subjects 30 years of age or more between January 1995 and March 2021, with a clinical diagnosis of gout or hyperuricemia (uric acid > 6.0 mg/dL), and at least one year baseline data.
From the base cohort, each subject who initiates allopurinol at or after base cohort entry. Will be matched with a reference non-user at the same time point (cohort entry) using a prevalent new-user design approach. The matching will be done on sex and time-conditional propensity scores. Matched subjects will be followed for up to 5 years or until the occurrence of death or a first cardiovascular event. The Cox proportional hazard model will be used to assess the effect of allopurinol use versus non-use on the incidence of cardiovascular events and mortality.
All-cause mortality; cardiovascular events (acute myocardial infarction, stroke)
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Afroza Begum - Collaborator - McGill University
Marie Hudson - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
Afroza Begum - Collaborator - McGill University
Marie Hudson - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care