Serum phosphorus levels and pill burden are inversely associated with adherence in patients on hemodialysis

Abstract

Background: Phosphate binders (PBs) account for about one half of the daily pill burden for US hemodialysis (HD) patients, which may reduce adherence. Adherence can be estimated by the medication possession ratio (MPR), which is defined as the proportion of time a patient had sufficient medication to have taken it as prescribed. Gaps of time between prescription fills lower the patient's MPR. We assessed the association of PB pill burden and adherence (MPR) with phosphorus goal attainment.

Methods: Using pharmacy management program data, HD patients on PB monotherapy were tracked from first PB fill during 1 January 2007-30 June 2011 for 1 year, or until PB change or censoring. Data were assessed with generalized linear models.

Results: We analyzed 8616 patients. Higher pill burden was associated with lower adherence. Lower adherence tended to be associated with higher mean phosphorus levels and lower percentage of patients with serum phosphorus ≤5.5 mg/dL (P < 0.001). The association between adherence and these clinical outcomes was most pronounced in the lowest and highest pill burden strata (<3, >3-6, >12-15, >15).

Conclusions: Adherence, as measured by the MPR, was negatively related to higher pill burden and phosphorus levels and positively related to patients in the phosphorus target range. Within pill burden strata, phosphorus increased and patients in the target range generally decreased with decreasing adherence, suggesting that patients prescribed fewer PB pills are less likely to have treatment gaps, and may be more likely to achieve phosphorus targets.

Keywords: adherence; hemodialysis; phosphate binders; pill burden; retrospective study.

FIGURE 1:

Pill burden, MPR and serum phosphorus calculated using the order method. (A) Weighted MPR by pill burden using the order method. The MPR was calculated as the days supplied in the period minus the excess days divided by the days covered by orders in the period. The mean MPR for each stratum is shown; P < 0.001 among strata by GLM; total n = 8616. Sample sizes for each pill burden stratum are shown at the base of the column. Error bars represent 95% confidence intervals (CIs). (B) Mean Phosphorus Levels Stratified by MPR using Order Method. Mean phosphorus concentration was calculated as the mean of per patient values for all tests of the period. Phosphorus means were weighted by the amount of patient–time contributed by each patient; P < 0.001 among strata by GLM; total n = 8616. Error bars represent 95% CIs. (C) Mean phosphorus by pill burden and MPR strata using the order method. Mean phosphorus was calculated as the mean of per patient values for all tests of the period. Phosphorus means were weighted by the amount of patient-time contributed by each patient. Lower MPR was associated with a higher mean phosphorus level (P < 0.001 among strata using GLM); a non-linear pattern emerged within the >6–9 and >9–12 pills/day strata. Error bars represent 95% CIs. (D) Percentage of patients with mean serum phosphorus ≤5.5 mg/dL by Pill Burden and MPR strata using the order method. The percentage of patients with phosphorus ≤5.5 mg/dL was calculated as the percentage of patients with an overall mean phosphorus of ≤5.5 mg/dL within the research period after censoring; total n = 8616. Higher MPR was positively associated with a higher percentage of patients with a serum phosphorus concentration of ≤5.5 mg/dL within each pill burden stratum (the difference was significant among strata, P < 0.001 using GLM analysis); in the >6–9 and >9–12 pills/day strata, a non-linear pattern was noted. Error bars represent 95% CIs.

FIGURE 2:

Weighted MPR by pill burden and mean phosphorus by pill burden and MPR strata using the patient-time method. (A) MPR was calculated as the days supplied in the period minus the excess days divided by the days in the period. Mean MPR for each stratum is shown; P < 0.001 among strata by GLM. Error bars represent 95% CIs. (B) Mean phosphorus was calculated as the mean of per patient values for all tests of the period. Phosphorus means were weighted by the amount of patient-time contributed by each patient; total n = 9346. Lower MPRwas associated with a higher mean phosphorus level (P < 0.001 among strata using GLM); a non-linear pattern emerged within the >6–9 and >9–12 pills/day strata. Error bars represent 95% CIs.

FIGURE 3:

Weighted MPR by pill burden and mean phosphorus by pill burden and MPR strata using the order method in patients using the RMS. (A) MPR was calculated as the days supplied in the period minus the excess days divided by the days covered by orders in the period. Mean MPR for each stratum is shown; P < 0.001 among strata by GLM. Error bars represent 95% CIs. (B) Mean phosphorus was calculated as the mean of per patient values for all tests of the period. Phosphorus means were weighted by the amount of patient-time contributed by each patient; total n = 26 279. Lower MPR was associated with a higher mean phosphorus level (P < 0.001 among strata using GLM); a non-linear pattern emerged within the >9–12, >12–15 and >15 pills/day strata. Error bars represent 95% CIs.