Allopurinol in CVD and CKD - ALL-HEART & CKD-FIX - Prof. Isla S Mackenzie and Prof. Sunil V. Badve

Prof. Isla Mackenzie and Prof. Sunil Badve present major findings from their ALL-HEART and CKD-FIX trials, which studied whether or not lowering of uric acid in patients without gout has benefits in secondary prevention of cardiovascular disease and for nephroprotection, respectively.
Isla Mackenzie is Professor of Cardiovascular Medicine and Honorary Consultant Physician at the University of Dundee and Ninewells Hospital, Dundee. Her major research interests include cardiovascular safety of drugs, clinical trials, hypertension and technology in research, and her major clinical interests include hypertension and adrenal disorders including phaeochromocytoma. Prof Mackenzie has been involved in leading a number of randomised clinical trials, including FAST, TIME and ALL-HEART, which tested whether allopurinol therapy reduces cardiovascular events in patients with ischemic heart disease without gout.
Sunil Badve is a nephrologist at St. George Hospital, Sydney and Conjoint Professor at UNSW Medicine and Health. His primary research focus are clinical trials, meta-analyses and epidemiology, particularly within the field of progression of chronic kidney disease, anticoagulation and treatment of cardiovascular disease in chronic kidney disease. He is lead author of the CKD-FIX trial, which tested the nephroprotective effects of allopurinol in CKD patients without gout.
The interview was recorded on July 20th, 2023.
Moderators: Prof. Dr. Kirsten de Groot (Offenbach, Germany), Ass.-Prof. Dr. Andreas Kronbichler (Innsbruck, Austria) and Prof. Dr. Gunnar Heine (Frankfurt, Germany).
Articles discussed:
Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial.
Mackenzie IS, Rogers A, Poulter NR, Williams B, Brown MJ, Webb DJ, Ford I, Rorie DA, Guthrie G, Grieve JWK, Pigazzani F, Rothwell PM, Young R, McConnachie A, Struthers AD, Lang CC, MacDonald TM; TIME Study Group. Lancet doi: 10.1016/S0140-6736(22)01786-X
Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial.
Mackenzie IS, Hawkey CJ, Ford I, Greenlaw N, Pigazzani F, Rogers A, Struthers AD, Begg AG, Wei L, Avery AJ, Taggar JS, Walker A, Duce SL, Barr RJ, Dumbleton JS, Rooke ED, Townend JN, Ritchie LD, MacDonald TM; ALL-HEART Study Group. Lancet. doi: 10.1016/S0140-6736(22)01657-9
Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial.
Mackenzie IS, Ford I, Nuki G, Hallas J, Hawkey CJ, Webster J, Ralston SH, Walters M, Robertson M, De Caterina R, Findlay E, Perez-Ruiz F, McMurray JJV, MacDonald TM; FAST Study Group. Lancet. 2020 doi: 10.1016/S0140-6736(20)32234-0
Effects of Allopurinol on the Progression of Chronic Kidney Disease.
Badve SV, Pascoe EM, Tiku A, Boudville N, Brown FG, Cass A, Clarke P, Dalbeth N, Day RO, de Zoysa JR, Douglas B, Faull R, Harris DC, Hawley CM, Jones GRD, Kanellis J, Palmer SC, Perkovic V, Rangan GK, Reidlinger D, Robison L, Walker RJ, Walters G, Johnson DW; CKD-FIX Study Investigators. N Engl J Med. 2020 doi: 10.1056/NEJMoa1915833
Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial.
Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Lancet. 2010 doi: 10.1016/S0140-6736(10)60391-1
Urate-Lowering Therapy and Chronic Kidney Disease Progression.
Feig DI. N Engl J Med. 2020 doi: 10.1056/NEJMe2015886
Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial.
Kimura K, Hosoya T, Uchida S, Inaba M, Makino H, Maruyama S, Ito S, Yamamoto T, Tomino Y, Ohno I, Shibagaki Y, Iimuro S, Imai N, Kuwabara M, Hayakawa H, Ohtsu H, Ohashi Y; FEATHER Study Investigators. Am J Kidney Dis. 2018 doi: 10.1053/j.ajkd.2018.06.028
Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.
White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, Hunt B, Castillo M, Gunawardhana L; CARES Investigators.
N Engl J Med. 2018 doi: 10.1056/NEJMoa1710895