Rohan Kumar Ochani  ( 4th Year Medical Students, Dow Medical College, Karachi Pakistan )
Farah Yasmin  ( 2nd Year Medical Student, Dow Medical College, Karachi Pakistan )
Simran Batra  ( 3rd Year Medical Student, Dow Medical College, Karachi Pakistan )
Ameema Asad  ( 4th Year Medical Students, Dow Medical College, Karachi Pakistan )

Madam, Hyperuricaemia (HU), characterized by raised serum uric acid levels (SUA), is a cause of substantial morbidity affecting 1-2% of the population globally with a prevalence of 39% in Pakistan of which 9.2% of the cases are reported to be asymptomatic.¹ According to a pooled analysis, HU was shown to be associated with ischaemic heart disease and higher SUA levels are a risk factor for dyslipidaemia and hypertension resulting in adverse cardiovascular events. ¹ Febuxostat — a non-competitive xanthine oxidase inhibitor has been increasingly prescribed for the potential management of hyperuricaemia with gout, after being approved by U.S. Food and Drug Administration (FDA) in 2009, ² with a better efficacy as compared to otherhyperuricaemic medications such as allopurinol. It has proved to significantly lower SUA levels with a success rate of 64% as compared to allopurinol (32%).³ Mechanically, it works by blocking the molybdenum pterin center- the active site on xanthine oxidase and thereby reduces the oxidation of xanthine to uric acid. ³ However recently in February 2019, FDA released a warning alert on a possible link between febuxostat and adverse cardiovascular events. ^4,5This boxed warning is based on the outcomes of a multicenter, randomized control study (CARES trial) comprising a cohort of 6000 gout patients, assigned to receive either febuxostat or allopurinol. ⁵ This non-inferiority trial was carried out to measure cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization as the primary outcome while death from all-causes and heart-related deaths were considered as secondary end points. ^4,5The primary endpoint was observed at similar rates in both febuxostat and allopurinol group, while all-cause mortality and cardiovascular mortality were observed to be higher in febuxostat group, sudden cardiac death being the most prevalent reported in 83 (2.7%) patients in the febuxostat group and 56 (1.8%) patients in the allopurinol group. ^4,5 Despite this warning issued by the FDA to limit the use of febuxostat, this drug is still being prescribed in many countries, including Pakistan. It is imperative that the physicians restrict the use of the drug only to patients for whom allopurinol has proved to be ineffective. Furthermore, physicians should prescribe this drug with caution among patients with gout and cardiovascular disease, and should inform patients of any possible cardiovascular-related adverse effects associated with febuxostat. They should be advised to immediately consult a physician, in case they experience any signs and symptoms associated with heart diseases such as chest pain, shortness of breath, rapid heartbeats. These and many more efforts are the need of the hour to reduce the modifiable causes of increasing burden of deaths due to cardiovascular events.

Disclaimer: None to declare.
Conflict of Interest: None to declare.

Funding Sources: None to declare.

References

1. Qidwai W, Jawaid M. Frequency of Uric Acid Levels, Symptomatic and Asymptomatic Hyperuricemia among the Pakistani Population. Middle East J Family Med. 2017; 15: 52-6.

2. Barclay L. FDA Approves Febuxostat for Chronic Management of Hyperuricemia in Patients With Gout. [Online] 2009 [Cited 2019 Mar 30]. Available from: URL:

https://www.medscape.com/viewarticle/588360.

3. Khan TA, Hussain A, Shakir L, Zaidi SA. COMPARISON OF XANTHINE OXIDASE INHIBITORS IN GOUTY PATIENTS WITH HYPERURICEMIA. Asian J Pharm Clin Res. 2016; 9: 183-6.

4. White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018; 378:1200-10.

5. U.S. Food & Drug Administration. FDA Drug Safety Communication: FDA to evaluate increased risk of heart-related death and death from all causes with the gout medicine febuxostat (Uloric) [Online] [Cited 2019 Mar 28]. Available from: URL:
https://www.fda.gov/drugs/drugsafety/ucm584702.htm.
DOI:10.5455/JPMA.42025.