Peter A. McCullough M.D.

Roger, S. D., P. T. Lavin, E. V. Lerma, P. A. McCullough, J. Butler, B. S. Spinowitz, S. von Haehling, M. Kosiborod, J. Zhao, S. Fishbane and D. K. Packham (2020). “Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study.” Nephrol Dial Transplant Feb 6. [Epub ahead of print].

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BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. METHODS: Adults with serum K+ >/=5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for /=30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). RESULTS: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, >/=30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and >/=30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 >/=30 mL/min/1.73 m2 subgroup. CONCLUSIONS: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Roger, S. D., P. T. Lavin, E. V. Lerma, P. A. McCullough, J. Butler, B. S. Spinowitz, S. von Haehling, M. Kosiborod, J. Zhao, S. Fishbane and D. K. Packham (2020). “Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study.” Nephrol Dial Transplant Feb 6. [Epub ahead of print].

Full text of this article.

BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. METHODS: Adults with serum K+ >/=5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for /=30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). RESULTS: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, >/=30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and >/=30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 >/=30 mL/min/1.73 m2 subgroup. CONCLUSIONS: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Oliveros, E., E. T. Oni, A. Shahzad, A. Y. Kluger, K. B. Lo, J. Rangaswami and P. A. McCullough (2020). “Benefits and Risks of Continuing Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Mineralocorticoid Receptor Antagonists during Hospitalizations for Acute Heart Failure.” Cardiorenal Med Feb 14:1-16. [Epub ahead of print].

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BACKGROUND: The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. SUMMARY: The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.

Cork, D. P., P. A. McCullough, H. S. Mehta, C. M. Barker, J. Van Houten, C. Gunnarsson, M. P. Ryan, E. R. Baker, S. Mollenkopf and P. Verta (2020). “The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.” J Med Econ Mar 2. [Epub ahead of print].

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Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age >/=18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

Cork, D. P., P. A. McCullough, H. S. Mehta, C. M. Barker, J. Van Houten, C. Gunnarsson, M. Ryan, E. Baker, S. Mollenkopf and P. Verta (2020). “The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.” J Med Econ Jan 17:1. [Epub ahead of print].

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Aim: This study aims to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM(R) MarketScan((R)) Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age >/=18 with a TR diagnosis, 12 months pre (baseline) and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately 1 inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.