SO033PATIROMER TO ENABLE SPIRONOLACTONE IN PATIENTS WITH RESISTANT HYPERTENSION AND CHRONIC KIDNEY DISEASE (AMBER): PRESPECIFIED RESULTS BY BASELINE SERUM POTASSIUM

Abstract Background and Aims Spironolactone (SPIRO) is effective at reducing blood pressure in patients with resistant hypertension (RHTN); however, its use in patients with advanced chronic kidney disease (CKD) is often limited by hyperkalaemia. In AMBER, patiromer (PAT) enabled more persistent use of SPIRO in patients with RHTN and eGFR 25 to ≤45 mL/min/1.73 m2. Patients were required to be normokalaemic at baseline, with serum potassium (sK+) 4.3 to 5.1 mmol/L. Since higher baseline sK+ may increase the risk for developing hyperkalaemia on SPIRO, we evaluated AMBER results in prespecified subgroups by baseline sK+. Methods This was a randomised, double-blind, placebo (PBO)-controlled trial in adults with eGFR 25 to ≤45 mL/min/1.73 m2, uncontrolled RHTN, and sK+ 4.3 to 5.1 mmol/L. Patients were assigned (1:1) to receive PBO or PAT, and SPIRO 25 mg QD, with dose titrations permitted after 1 week (PAT) and 3 weeks (SPIRO). The primary endpoint was the between-group difference at Week 12 in the percentage of patients on SPIRO. The secondary endpoint was the difference between treatment groups in the change in systolic automated office blood pressure (AOBP) from baseline to Week 12 (or to the last available measurement before the addition of any new antihypertensive medications or increase in any of the baseline antihypertensive medications). The primary and secondary endpoints were assessed in prespecified subgroups by baseline sK+ stratum: 4.3 to <4.7 mmol/L and 4.7 to 5.1 mmol/L. Results 295 patients were randomised, 129 (44%) and 166 (56%) with baseline sK+ 4.3 to <4.7 mmol/L and sK+ 4.7 to 5.1 mmol/L, respectively. Baseline mean (SD) systolic AOBP (mmHg) was 144.0 (7.3) and 144.1 (6.4), and eGFR (mL/min/1.73 m2) was 36.4 (7.6) and 35.2 (7.2), respectively. Significantly more patients treated with PAT than with PBO remained on SPIRO at Week 12 in both subgroups (between treatment difference of 16.2% [P=0.0167] for patients with sK+ 4.3 to <4.7 mmol/L and 22.4% [P=0.0016] for patients with sK+ 4.7 to 5.1 mmol/L) with P=0.45 for interaction between subgroups (Figure). In patients with sK+ 4.3 to <4.7 mmol/L, LS mean (SE) systolic AOBP change from baseline was –10.7 (1.9) mmHg in patients receiving PBO and –13.0 (1.9) mmHg in patients receiving PAT; systolic AOBP change from baseline was –10.5 (1.6) (PBO) and –10.5 (1.6) mmHg (PAT) in patients with sK+ 4.7 to 5.1 mmol/L (P<0.001 for all changes from baseline and P=NS for all differences between treatment groups). LS mean (SE) cumulative SPIRO dose was higher with PAT than PBO by 373.2 (157.0) mg and 392.3 (185.0) mg in patients with sK+ 4.3 to <4.7 mmol/L and sK+ 4.7 to 5.1 mmol/L, respectively. Adverse events occurred in 52% (PBO) and 56% (PAT) of patients with sK+ 4.3 to <4.7 mmol/L and in 55% (PBO) and 56% (PAT) of patients with sK+ 4.7 to 5.1 mmol/L. Adverse events of hyperkalaemia or blood K+ increased occurred in 2 (PBO) and 4 (PAT) patients with sK+ 4.3 to <4.7 mmol/L and in 12 (PBO) and 5 (PAT) patients with sK+ 4.7 to 5.1 mmol/L. One PBO and 2 PAT patients (sK+ 4.3 to <4.7 subgroup) and 1 PAT patient (sK+ 4.7 to 5.1 subgroup) had serum Mg 0.49 to <0.58 mmol/L; none had serum Mg <0.49 mmol/L. Conclusion PAT enabled more patients with advanced CKD and RHTN to continue treatment with SPIRO, regardless of baseline sK+ stratum.