Hyperuricemia is not the sole driver of CVD risk and the persistent premature mortality observed in patients with gout, despite the narrative forged in observational studies over many years.
Speaking at ACR Convergence 2023 in San Diego, Professor Nicola Dalbeth said recent randomised studies have not supported elevated serum urate as causal for cardiovascular disease.
As an example, the 2022 ALL-HEART study [link here] in a large population with ischaemic heart disease but no gout found allopurinol up to 600 mg/day was effective urate lowering therapy but had no impact on the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death compared to usual care.
“What we don’t know at this stage is whether there is the same lack of effect in people with gout. But … are we actually looking in the wrong place?”
Professor Dalbeth, from the University of Auckland and Auckland District Health Board, said a 2022 nested case-control study [link here] found a higher odds of either acute myocardial infarction or stroke soon after a gout flare.
“So maybe it’s not the urate; maybe it’s actually the acute inflammation that’s contributing.”
She said a number of studies had demonstrated cardiovascular benefits from low dose colchicine in post-MI and stable CVD populations. The question was whether there were similar benefits in gout patients.
“Certainly we really need more data … looking at whether there is in fact a cardiovascular benefit of low dose colchicine, specifically in the gout setting.”
Similarly, there was evidence for the cardiovascular benefits of canakinumab in the general population but not yet for CV benefits in gout patients.
Professor Dalbeth said evidence was building for the potential benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2is) as a treatment approach for the comorbidities seen with gout.
A recent 2023 Canadian study in patients with gout and type 2 diabetes [link here] found SGLT2is reduced recurrent flares and gout-related ED visits and hospitalisations and may provide cardiovascular benefits when compared to glucagon like peptide-1 receptor agonists (GLP-1 RA) or dipeptidyl peptidase-4 inhibitors (DPP-4i).
As well, a second 2023 study using a UK primary care database [link here] found SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators of GLP-1 RA and DPP-4i in patients with gout and type 2 diabetes.
“And I think these are really a very exciting class when we’re thinking about the comorbidities that we often see in people with gout.”
“More and more we should be thinking about, not just the gout management but also management of cardiometabolic complications. I think we do need to be thinking about systematic programs of cardiovascular and CKD risk reduction for people with gout. We do need to be thinking about intensive management of traditional risk factors.”
Professor Dalbeth said she did not want colleagues to think there wasn’t still a role for urate lowering therapy.
“Effective urate lowering therapy needs to be part of the program as well. Certainly we know that effective gout therapy prevents gout flares over time. It also reduces exposure to NSAIDs and corticosteroids.”
“And I think what we often see is that effective gout management enables much better control of other health issues. So, often we see patients getting really good control of their gout and then being activated to take control of other aspects of their health.”