Table 1.

Clinical trials for the efficacy of therapeutic agents of gout in cardiovascular risks.

Drugs	Study Design	Control	Participants	Number	Results
Allopurinol	RCT [107]	Usual therapy	Patientis with CKD (eGFR < 60 mL/min).	113	Allopurinol slows down the progression of renal disease and reduces risk of cardiovascular events by 71%.
	RCT [108]	Placebo	Adults with stage 3 or 4 CKD and no history of gout.	369	Allopurinol did not slow the decline in eGFR as compared with placebo.
	Meta-analysis: 12 RCTs [123]	Placebo or no treatment	RCTs investigated allopurinol’s effects on endothelial function. Patients with CHF, CKD, or type 2 DM.	CHF; 197 CKD; 183 DM; 170	Allopurinol had a benefit on endothelial function in patients with CHF and CKD but not in type 2 DM.
	Meta-analysis: 9 RCTs [109]	Placebo or control	Patients undergoing CABG, after ACS or CHF.	850	Allopurinol was associated with the reduction of odds of periprocedural ACS but not with that of long-term secondary prevention of ACS.
Febuxostat	RCT [116]	Allopurinol	Patients with gout and cardiovascular disease.	6190	All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (HR for all death, 1.22; HR for cardiovascular death, 1.34).
	RCT [117]	Allopurinol	Patients were ≥60 y.o., already receiving allopurinol, and had at least one additional cardiovascular risk factor.	6128	Febuxostat is non-inferior to allopurinol therapy as the primary cardiovascular endpoint and not associated with an increased risk of death.
Xanthine oxidase inhibitor (XOI)	Meta-analysis: 81 RCTs [119]	Placebo or no treatment	RCTs comparing purine-like or non-purine XOI with placebo or no treatment (control) for a period equal or superior to 28 days in adult patients.	10,684 (6434 pt·yr)	XOI did not significantly reduce the risk of MACE and death but reduced the risk of TCE and hypertension.
Urate-lowering treatment (ULT)	Meta-analysis: 18 RCTs [120]	Placebo or other ULT drugs	RCTs had to report cardiovascular safety of urate-lowering treatment (allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone).	7757	Any ULT did not demonstrate a significant difference in any cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, or all-cause mortality.
Colchcine	RCT [122]	Placebo	Patients suffered from MI within 30 days.	4745	The primary endpoint occurred at 5.5% in the colchicine group compared with 7.1% in the placebo group (HR 0.77, 95% CI 0.61–0.96).
	RCT [89]	Placebo	Patients had any evidence of coronary disease and have been in a clinically stable condition for at least 6 months.	5522	A primary endpoint event occurred in 6.8% in the colchicine group and 9.6% in the placebo group (HR 0.69, 95% CI 0.57–0.83).

RCT, randomized controlled trial; CKD, chronic kidney disease; CHF, chronic heart failure; DM, diabetes mellitus; CABG, coronary artery bypass graft; ACS, acute coronary syndrome; MI, myocardial infarction; pt·yr, patient-years; HR, hazard ratio; CI, confidence interval; MACE, major adverse cardiovascular event; TCE, total cardiovascular event.