Hyperkalemia Is an Underestimated Risk Factor in COPD

Jukka Mäenpää,1 Isobel Anderson,2 Caroline A Owen,3 Ulrika Emerath,1 Rod Hughes,4 Stefan R Sultana,5 Marita Olsson6 1Chief Medical Office, Research & Development, Patient Safety Biopharma, AstraZeneca, Gothenburg, Sweden; 2Patient Safety Operations, Technology & Analytics, Global Patient Safety, AstraZeneca, Macclesfield, UK; 3BioPharmaceuticals, Early Clinical Development, AstraZeneca, Gaithersburg, MD, USA; 4BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 5Cardiovascular Safety Center of Excellence and Safety Knowledge Groups, Global Patient Safety, AstraZeneca, Cambridge, UK; 6BioPharma Late-Stage Development Respiratory & Immunology, Biometrics and Statistical Innovation, AstraZeneca, Gothenburg, SwedenCorrespondence: Jukka Mäenpää, Chief Medical Office, Research & Development, Patient Safety Biopharma, AstraZeneca, Gothenburg, SE-431 83, Sweden, Tel +46-730-715488, Email [email protected]: Hyperkalemia increases mortality in various patient populations. The risk of hyperkalemia in COPD patients is poorly recognized. Hyperkalemia may increase cardiovascular mortality during and soon after COPD exacerbations.Patients and Methods: A cohort based on two clinical trials comprising 7968 patients with moderate-to-very severe COPD was analysed retrospectively for associations between hyperkalemia and common comorbidities such as chronic kidney disease, diabetes mellitus (DM), or renin-angiotensin-aldosterone system inhibitor use.Results: Overall, 6.4% of 7968 patients had hyperkalemia (5.3% Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2, 6.8% GOLD 3, and 8.0% GOLD 4). COPD severity was associated with significantly higher hyperkalemia risk in GOLD 3 (odds ratio [OR]=1.28, 95% CI 1.04– 1.58) and GOLD 4 (OR=1.64, 95% CI 1.19– 2.22) versus GOLD 2 patients. Hyperkalemia cases increased with decreasing renal function. Patients with moderate-to-severe renal impairment had > 2-fold increased hyperkalemia risk versus those with normal renal function (OR=2.29, 95% CI 1.71– 3.04). DM was associated with increased hyperkalemia risk (OR=1.28, 95% CI 1.02– 1.59). Angiotensin-converting-enzyme inhibitor (ACEi) use increased hyperkalemia risk (OR=1.25, 95% CI 1.02– 1.53). Unexpectedly, the association between hyperkalemia and renin-angiotensin-aldosterone system inhibitor use was statistically significant only in the normal renal function group (OR=1.63, 95% CI 1.13– 2.34).Conclusion: Hyperkalemia risk is higher in severe and very severe COPD patients than patients with moderate COPD. Hyperkalemia was also associated with decreasing kidney function, DM, and ACEi use. Serum potassium levels should be monitored regularly in patients with COPD, particularly those with GOLD-3 and 4.Keywords: cardiac arrhythmias, chronic kidney disease, angiotensin-converting-enzyme inhibitor, renin-angiotensin-aldosterone system inhibitors, serum bicarbonates