Modeling Hyperkalaemia Event Rates and Impacts

The occurrence of HK was categorized as a serum potassium level greater than 5 mmol/l, consistent with the definitions used in the OPAL-HK trial and widely accepted in the broader HK literature [29 (link), 44 (link)]. Events were further stratified by severity (i.e., 5–5.5 mmol/l, 5.5–6 mmol/l and > 6 mmol/l). During the first three months of the modelled time horizon, incident HK events are predicted based on data from the OPAL-HK trial [29 (link), 45 (link)]. For all subsequent months, annual rates of HK were obtained from Horne et al. (2019) and applied to the SoC arm [46 (link)]. Hazard ratios relating to reduced (or increased) incidence in those receiving patiromer in subsequent years were obtained from the OPAL-HK trial and applied to the annual rates of HK obtained from Horne et al. (2019). HK event rates are summarised in Table 2. Increased potassium levels negatively impact the incidence of MACE, hospitalisation and death (Fig. 2); the magnitude of these impacts is further described in Supplemental Appendix A.Table 2

HK incidence

Time applied	Potassium level	Monthly probability				Source
		Patiromer		SoC
		Mean	SE	Mean	SE
Month 1	K +  > 5 to ≤ 5.5	21.13%	3.32%	21.13%	3.32%	OPAL-HK CSR; distributed across threshold categories in line with published data [43 , 46 (link)]
	K +  > 5.5 to ≤ 6	1.66%	1.04%	1.66%	1.04%
	K +  > 6	0.38%	0.50%	0.38%	0.50%
Month 2 & 3	K +  > 5 to ≤ 5.5	14.00%	4.68%	15.00%	4.81%	OPAL-HK CSR [43 ]
	K +  > 5.5 to ≤ 6	6.10%	3.23%	25.22%	5.86%
	K +  > 6	1.40%	1.58%	5.78%	3.15%
Subsequent monthsa	K +  > 5 to ≤ 5.5	0.543%	0.054%	1.158%	0.116%	Horne et al. (2019); 'OPAL-HK CSR [43 , 46 (link)]
	K +  > 5.5 to ≤ 6	0.022%	0.002%	0.092%	0.009%
	K +  > 6	0.005%	0.001%	0.021%	0.002%

HK Hyperkalaemia, RAASi Renin–angiotensin–aldosterone system inhibitor, SE Standard error, SoC Standard of care

^aSoC probabilities informed by HK recurrence rates observed in Horne et al. (2019) with recurrence events distributed in line with the distribution of initial HK events across potassium categories; patiromer estimates informed by Horne et al. (2019) after application of a HR based on OPAL-HK data from months 2 and 3; SE assumed as 10% of mean

Fig. 2

Influence of RAASi use and HK events on disease progression and events. References below each box describe the baseline probabilities/rates; references alongside arrows describe the influence of one disease component on the other, with influences applied to the baseline probabilities rates