Researchers suggest from these findings that because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.
This is one of two large observational studies published in JAMA Internal Medicine, using administrative data to examine the safety of older medications that are sometimes withheld from patients thought to be at higher risk of harm. The other population-based study was of NSAID prescribing in patients with hypertension, heart failure, or CKD.
A commentary notes that unsurprisingly, the safety of NSAIDs and allopurinol in high-risk populations such as these has not been established in RCTs. It acknowledges that although there is reliance on observational studies to answer questions poorly suited to clinical trials, these findings have to be interpreted with caution as causation cannot be established from these associations. It discusses some of the caveats of these new studies, such as whether patients who received NSAIDs or allopurinol were otherwise similar to those who did not. When treatment allocation is non-random, it raises the possibilities of selection bias and confounding by indication. Perhaps the drugs were preferentially prescribed to patients destined to tolerate them, or fare better in some other way apparent to prescribers but beyond the resolution of large databases. It adds that the use of propensity-score matching can generate a nicely balanced Table 1, but it is important to realize that differences are likely to persist between treated and untreated patients, and not all differences are measurable.
It adds that the bigger issue is how these studies should influence practice, if at all, as clinicians already recognize that many patients with heart failure, kidney disease, or hypertension tolerate a short course of NSAIDs without obvious harm, and that in many patients with gout, higher doses of allopurinol can be prescribed without concerns about progression of CKD. It suggests that on balance, these data “help soften our stance on the use of NSAIDs and allopurinol in patients with relative contraindications.” It concludes that done well, observational studies can provide valuable information about the real-world safety of drugs, though the findings will need to be contextualized and viewed with more skepticism than RCTs, but in some instances, it suggests they can be thoughtfully integrated into treatment decisions.