No matter how it was initiated or dosed, the anti-gout drug allopurinol did not increase mortality risk in patients with both gout and chronic kidney disease (CKD), a population-based study affirmed.
In a cohort of 5,277 patients who had initiated allopurinol, mortality was actually slightly lower, at an incidence rate of 4.9 per 100 person-years during 5 years of follow-up, than in the same number of non-initiators, among whom the mortality rate was 5.8 per 100 person-years over the same 5 years period (hazard ratio [HR] 0.85 [95% CI, 0.77-0.93]), Guanghua Lei, MD, PhD, Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Annals of Internal Medicine.
Emulation of a target randomized controlled trial (RCT) in allopurinol initiators showed that the risk of mortality was again slightly lower at an HR of 0.87 (95% CI, 0.75-1.01) for patients who achieved a target serum urate level of less than 0.36 mmol/L compared to patients who did not achieve target serum urate levels.
Furthermore, the risk of mortality was virtually identical at an HR of 0.88 (95% CI, 0.73-1.07) for patients in whom the dose of allopurinol was escalated compared to patients in whom no dose escalation took place.
“[N]o previous study has assessed the effect of allopurinol initiation on mortality, specifically in patients with both gout and CKD,” Lei and colleagues observed.
“These findings provide empirical evidence that adopting current gout treatment guidelines does not seem to have a detrimental effect on mortality in patients with both gout and CKD,” they added.
Data from the Health Improvement Network (THIN), an electronic health records database which contains health records of approximately 17 million patients in the United Kingdom, was used to carry out the study.
Patients were 40 to 89 years of age (mean age 74) and had gout and concurrent moderate-to-severe CKD, 40% were female, and the mean baseline serum urate level was 0.52 mmol/L, while the mean estimated glomerular filtration rate (eGFR) was 47.5 mL/min/1.73 m2.
Initially, investigators did a propensity score (PS)-matched cohort study to compare mortality between allopurinol initiators versus non-initiators. They then emulated analyses of a target clinical trial to assess the effect of patients achieving target serum urate levels as well as the effect that dose escalation had on mortality risk between allopurinol users versus non-users.
At 5 years of follow-up, the mean final level of serum urate was 0.42 mmol/L among initiators versus a mean of 0.48 mmol/L among non-initiators, investigators reported.
Mean levels of eGFR again during the 5-year follow-up were very similar between initiators and non-initiators at a mean of 47.2 mL/min/1.73 m2 and 46.1 mL/min/1.73 m2, respectively.
However, among those who did achieve the target serum urate level of <0.36 mmol/L, the final mean serum urate level was 0.30 mmol/L during the 5 years follow-up at a final dose of allopurinol, 300 mg/day.
Among those participants who did not achieve the target serum urate level within the first year, one-third discontinued treatment after the first prescription, investigators pointed out.
As the authors discuss, results from two RCTs — one from Badve et al and the other from Doria et al—demonstrated that allopurinol had no benefit on kidney function in patients with renal disease but not gout.
“Unexpectedly, both trials and pooled analyses indicated that allopurinol was associated with a 2-fold increase risk for death in patients with renal disease,” they noted.
Thus, the current study’s findings are “clinically relevant” in gout care because CKD is a common comorbidity of gout and allopurinol is still the most widely used urate-lowering medication despite the availability of newer alternatives, the investigators suggested.
Allopurinol is also still largely started at a low dose, which is increased over weeks to months to achieve and maintain a serum urate level below that needed to form crystals and then is continued indefinitely.
“[F]indings from [the] 2 recent RCTs that allopurinol use may increase mortality in participants without gout but with CKD have raised concerns about whether a treat-to-target approach of lowering SU (serum urate) level would be safe for patients with gout and concurrent CKD,” the authors observed.
“To that end, our findings provide reassurance that the treat-to-target approach of lowering serum urate does not have a detrimental effect on mortality in patients with both gout and CKD,” they concluded.
Disclosure:
The study was funded by the Project Program of National Clinical Research Center for Geriatric Disorders.
Wei disclosed no relevant relationships.
by
Pam Harrison, Contributing Writer, BreakingMED™
Kaiser Health News
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.
