Real-world evidence study shows the significant impact of hyperkalaemia on cardiorenal patient outcomes

AstraZeneca’s real-world evidence (RWE) ZORA study shows the negative consequences of reducing or discontinuing life-saving renin-angiotensin-aldosterone system inhibitor (RAASi) medication in patients experiencing hyperkalaemia (HK).^1-2

One analysis from the ZORA study presented at the European Renal Association (ERA) 2023 Congress in Milan, Italy, showed that discontinuation of RAASi treatment following a HK episode in cardiorenal patients with chronic kidney disease (CKD) and/or heart failure (HF) was still common in clinical practice in the US and Japan despite guidelines recommending maintained treatment.¹ In those patients who discontinued, re-initiation occurred within six months in only 10% to 15% of patients in the US and among 6% to 8% of patients in Japan.¹ In the small number who re-initiated RAASi, 17% to 37% of patients in the US and Japan respectively, had their dose reduced by >25%.¹

A second analysis found that in cardiorenal patients living in Sweden and Japan, reduced RAASi treatment following a HK episode resulted in an increased number of all-cause hospital inpatient days by 18.2 days in Sweden (n=6,998) and 17.9 days in Japan (n=2,092), six months after the HK event.² The increase in hospital days in patients who maintained their RAASi treatment, versus six months post the HK event, was 9.4 and 8.5 days in Sweden and Japan, respectively.² Similar patterns were observed for CKD- and HF-related hospital inpatient days.²

Anjay Rastogi, M.D., Ph.D., Clinical Chief of Nephrology, UCLA Health, said: “Cardiorenal patients face a serious, unmet need in controlling hyperkalaemia, leading to higher cardiac risk and incidence of hospitalisations. These powerful real-world data show how common it is for hyperkalaemia to cause down-titration of guideline-recommended RAASi therapy in cardiorenal patients. Hyperkalaemia should not be a barrier to patients with chronic kidney disease or heart failure achieving guideline directed RAASi treatment, especially when there are treatment options, like potassium binders, which may better manage this chronic condition.”

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Failing to achieve guideline-directed RAASi therapy can have serious consequences for cardiorenal patients, yet these findings highlight how rarely these patients resume treatment following hyperkalaemia-related discontinuation, and the urgent need for practice change in hyperkalaemia management to enable this. We’re committed to improving the treatment of hyperkalaemia through anti-hyperkalaemia therapies and working with the healthcare community more broadly to help deliver better cardiorenal protection for patients.”

These two analyses build on a ZORA manuscript published in BMC Nephrology, which found that HK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi in patients with CKD or HF in the US and Japan.³

Notes

Hyperkalaemia
Hyperkalaemia (HK), an acute or  chronic condition, is characterised by high levels of potassium in the blood, generally defined as greater than 5 mmol/L.^4-5 Patients with high potassium levels are at significant risk of arrhythmias, which can lead to cardiac arrest.⁶ Worldwide there are about 850 million and 64 million people living with CKD and HF, respectively, who are at an estimated 2 to 3 times higher risk of HK.^7-11 RAASi therapy is guideline-recommended to slow CKD progression and reduce CV events, but it is often lowered or discontinued when HK is diagnosed.^12-15 This has been shown to negatively impact patient outcomes, with mortality rates doubled for patients with CKD and HF whose RAASi had been down-titrated or discontinued compared to patients on maximum RAASi dose.¹⁶

ZORA
The ZORA study is part of the CRYSTALIZE evidence programme, which is examining the current management of HK. It is comprised of industry-leading clinical and RWE studies across different disease areas and patient types.

One analysis from the ZORA study titled Suboptimal extent of RAASi re-initiation after discontinuation following hyperkalemia assesses the extent of both temporary and longer-term discontinuation of RAASi following a HK episode, and the magnitude of RAASi re-initiation. Data from hospital records and claims from 34,685 cardiorenal patients in the US (n=25,963) and Japan (n=8,722) with an index HK event during July 2019 and September 2021 (US) or May 2020 and February 2022 (Japan), with CKD and/or HF and baseline RAASi use were included.¹

Another analysis titled Increase in hospitalized days after hyperkalemia-related reduction in RAASi use describes the extent of RAASi reduction (down-titration or discontinuation) following a HK episode, and the associated change in the number of all-cause, CKD-, and HF-related inpatient days. Using data from health registers and hospital records, the study includes 28,613 cardiorenal patients from Sweden (n=20,824) and Japan (n=7,789) who had an index HK event during March 2018 and July 2020 (Sweden) or May 2020 and February 2022 (Japan) with CKD and/or HF and baseline RAASi use.²

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

1. Kanda E et al. Suboptimal Extent of RAASi Re-Initiation After Discontinuation Following Hyperkalemia: an Observational Study of Cardiorenal Patients in US and Japan. Presented at: ERA 2023 Congress; 2023 June 15-18; Milan, Italy.

2. Svensson M et al. Increase in hospitalized days after hyperkalemia-related reduction in RAASi use: An observational study on cardiorenal patients in Sweden and Japan. Presented at: Presented at: ERA 2023 Congress; 2023 June 15-18; Milan, Italy.

3. Kanda, et al. Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia. BMC Nephrol 24, 18 (2023). https://doi.org/10.1186/s12882-022-03054-5  

4. Thomsen RW, et al. Elevated potassium levels in patients with chronic kidney disease; occurrence, risk factors and clinical outcomes – a Danish population-based cohort study. J Am Heart Assoc. 2018;7:e008912.

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9. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239.

10. Jager KJ, et al. A Single Number for Advocacy and Communication—Worldwide More than 850 Million Individuals Have Kidney Diseases. Nephrol Dial Transplant. 2019;34(11):1803-5. 

11. Vos T, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2017; 390(10100):1211–59. 

12. McDonagh TA ,et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.

13. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421.

14. Collins AJ,  et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3):213-221.

15. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney Int. 2022;102(5S):S1-S127.

16. Epstein et al. Evaluation of the Treatment Gap Between Clinical Guidelines and the Utilization of Renin-Angiotensin Aldosterone System Inhibitors. Am J Manag Care. 2015;21(11 suppl):S212-S220.