ABSTRACT
Background: Metformin-associated lactic acidosis occurs very infrequently;however, with the significantly greater comorbidity burden and acuity of patients with diabetes undergoing coronary angiography/angioplasty (CA), the inherent risk of metformin-associated lactic acidosis may be significantly increased. Additionally, significant variations in contemporary practice pattern around peri-CA metformin use still continue to exist. Methods and Results: This is a pilot, single-center, open-labelled, randomized comparison of metformin continuation or 48-hour interruption following CA (Saskatoon, Clinical Trials.gov 03980990). All patients had metformin continued to the time of the angiogram. Patients presenting with cardiogenic shock, cardiac arrest, history of chronic liver disease, severe chronic kidney disease (eGFR<30 or on dialysis) or requiring coronary artery bypass graft surgery following CA were ineligible for inclusion. Planned enrollment of 500 patients had been anticipated for the calendar year (June 2019-June 2020), and stratified at randomization by in/out-patient status. The primary outcome included lactic acidosis (lactate ≥5mmol/L ± bicarbonate <18mmol/l) at 48-72 hours after CA. Key secondary outcomes included: absolute lactate levels, acute kidney injury (AKI, ≥25% or 27μmol/L rise at 48-72 hours) and all-cause mortality at 1-week. Continuous variables are expressed as medians (25th, 75th percentile) and categorical variables as frequency (%). At study interruption (March 12/20, COVID-19) 312 patients had been randomized, of whom 52% presented with an acute coronary syndrome (n= 161/312;STEMI 11%). Baseline characteristics were balanced across the two groups, including the proportion treated with PCI (Table 1). Follow up lactate levels were available in: continued arm 71% (n=112/157), interrupt arm 67% (n=104/155). No patients in either arm had serum lactate ≥5mmol/L, however, metformin continuation compared with a 48-hour interruption had significantly higher median lactate levels (1.70 [1.15, 2.2] vs. 1.40 [1.2, 1.8], p=0.02);no between-group differences were evident for serum bicarbonate (26.0 [24, 28] mmol/L vs. 25.0 [24, 27] mmol/l, p=0.15). No differences were evident in the rates of AKI (7.7% vs. 8.3% p= 1.0). No patients died in either treatment arm at 1-week (vital status available for all 312 patients). Conclusion: Conclusion: In this interim analysis of contemporary treated patients with diabetes, all of whom had metformin continued up to CA, metformin continuation compared with a 48-hour interruption was not associated with clinically relevant lactic acidosis. Continued metformin use however appears to associate with higher 48-72-hour lactate levels, without differences in AKI or all-cause mortality at 1-week. Trial completion is anticipated with COVID-19 pandemic resolution. [Formula presented] Royal University Hospital Foundation