Joost C Beusekamp1, Jasper Tromp1,2, Haye H van der Wal1, Stefan D Anker3,4, John G Cleland5, Kenneth Dickstein6,7, Gerasimos Filippatos8, Pim van der Harst1, Hans L Hillege1, Chim C Lang9, Marco Metra10, Leong L Ng11, Piotr Ponikowski12, Nilesh J Samani11, Dirk J van Veldhuisen1, Aeilko H Zwinderman13, Patrick Rossignol14, Faiez Zannad14, Adriaan A Voors1, Peter van der Meer1. 1. Department of Cardiology, University of Groningen, Groningen, The Netherlands. 2. National Heart Centre Singapore, Singapore. 3. Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany. 4. Division of Cardiology and Metabolism-Heart Failure, Cachexia and Sarcopenia, Department of Cardiology, and Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany. 5. National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK. 6. University of Bergen, Bergen, Norway. 7. Stavanger University Hospital, Stavanger, Norway. 8. National and Kapodistrian University of Athens, School of Medicine and Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 9. School of Medicine Centre for Cardiovascular and Lung Biology, Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. 10. Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 11. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. 12. Department of Heart Diseases, Wroclaw Medical University, Poland, and Cardiology Department, Military Hospital, Wroclaw, Poland. 13. Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. 14. Inserm CIC-P 1433, Université de Lorraine, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France.
Abstract
BACKGROUND: Hyperkalaemia is a common co-morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Whether it affects the use of renin-angiotensin-aldosterone system inhibitors and thereby negatively impacts outcome is unknown. Therefore, we investigated the association between potassium and uptitration of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and its association with outcome. METHODS AND RESULTS: Out of 2516 patients from the BIOSTAT-CHF study, potassium levels were available in 1666 patients with HFrEF. These patients were sub-optimally treated with ACEi/ARB or beta-blockers and were anticipated and encouraged to be uptitrated. Potassium levels were available at inclusion and at 9 months. Outcome was a composite of all-cause mortality and heart failure hospitalization at 2 years. Patients' mean age was 67 ± 12 years and 77% were male. At baseline, median serum potassium was 4.3 (interquartile range 3.9-4.6) mEq/L. After 9 months, 401 (24.1%) patients were successfully uptitrated with ACEi/ARB. During this period, mean serum potassium increased by 0.16 ± 0.66 mEq/L (P < 0.001). Baseline potassium was an independent predictor of lower ACEi/ARB dosage achieved [odds ratio 0.70; 95% confidence interval (CI) 0.51-0.98]. An increase in potassium was not associated with adverse outcomes (hazard ratio 1.15; 95% CI 0.86-1.53). No interaction on outcome was found between baseline potassium, potassium increase during uptitration, or potassium at 9 months and increased dosage of ACEi/ARB (Pinteraction > 0.5 for all). CONCLUSION: Higher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of ACEi/ARB uptitration.
BACKGROUND:Hyperkalaemia is a common co-morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Whether it affects the use of renin-angiotensin-aldosterone system inhibitors and thereby negatively impacts outcome is unknown. Therefore, we investigated the association between potassium and uptitration of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and its association with outcome. METHODS AND RESULTS: Out of 2516 patients from the BIOSTAT-CHF study, potassium levels were available in 1666 patients with HFrEF. These patients were sub-optimally treated with ACEi/ARB or beta-blockers and were anticipated and encouraged to be uptitrated. Potassium levels were available at inclusion and at 9 months. Outcome was a composite of all-cause mortality and heart failure hospitalization at 2 years. Patients' mean age was 67 ± 12 years and 77% were male. At baseline, median serum potassium was 4.3 (interquartile range 3.9-4.6) mEq/L. After 9 months, 401 (24.1%) patients were successfully uptitrated with ACEi/ARB. During this period, mean serum potassium increased by 0.16 ± 0.66 mEq/L (P < 0.001). Baseline potassium was an independent predictor of lower ACEi/ARB dosage achieved [odds ratio 0.70; 95% confidence interval (CI) 0.51-0.98]. An increase in potassium was not associated with adverse outcomes (hazard ratio 1.15; 95% CI 0.86-1.53). No interaction on outcome was found between baseline potassium, potassium increase during uptitration, or potassium at 9 months and increased dosage of ACEi/ARB (Pinteraction > 0.5 for all). CONCLUSION: Higher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of ACEi/ARB uptitration.
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