Background: Down-titration or discontinuation of renin-angiotensin-aldosterone system inhibitors (RAASi) is common practice to reduce iatrogenic hyperkalaemia (HK) in heart failure (HF) patients. However, RAASi dose modification may reduce its cardio-renal protection.
Purpose: To study RAASi dosing in HF patients, including the association between HK and down-titration/discontinuation of RAASi therapies.
Methods: Data from the UK Clinical Practice Research Datalink identified patients with a new diagnosis of HF from Jan 2006 to Dec 2015 without chronic kidney disease (stage 3+). Serum potassium (K+) was time-updated during follow-up. HK was categorised using the thresholds K+ ≥5.0, ≥5.5 and ≥6.0 mmol/L; normokalaemia was defined as K+ 3.5 to <5.0 mmol/L. RAASi therapies included ACEi, ARBs and MRAs. Outcomes included: prescribed RAASi daily dose (DD) as a percentage of ESC-recommended DD; down-titration, defined as a decrease in prescribed DD between successive prescriptions; and discontinuation, defined as a minimum 90-day gap in the supply. DDs were assessed within 7 days from each K+ measurement. Generalized Estimating Equations were used to estimate adjusted odds ratios (ORs) relating RAASi down-titration/discontinuation to HK whilst controlling for confounders, including patient demographics, clinical measurements (e.g. eGFR), and concomitant medications.
Results: Of 21,334 eligible HF patients, 13,113 (61%) received RAASi during follow-up (mean follow-up 5.1 years). At baseline, the mean age was 73 years, 60% male, and 16%, 12% and 7% had diabetes, myocardial infarction or stroke, respectively. During follow-up, 5,580 (43%), 2,070 (16%) and 601 (5%) patients experienced at least one HK event at K+ ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. Prescriptions recorded for ACEi, ARBs and MRAs were 250,842 (54%), 92,569 (20%) and 118,079 (26%), respectively. In 65% of patients, prescribed RAASi DD was less than 100% of ESC-recommended dose, with 26% prescribed less than 50% of recommended. RAASi dose was reduced in 4%, 6% and 9% of prescriptions issued within 7 days of K+ measurements of ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively, compared to 3% of prescriptions during normokalaemia. The corresponding percentages of RAASi discontinuation were 4%, 6% and 10% after K+ measurements of ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively, compared to 3% during normokalaemia. Figure 1 illustrates ORs for RAASi down-titration and discontinuation, comparing patients with and without HK at different K+ thresholds, after controlling for covariates.
Conclusion: In this real-world HF cohort analysis, most patients were below recommended RAASi daily dose. The likelihood of down-titration post HK was significantly associated with, and proportional to the magnitude of elevated K+. Therapies to manage HK would allow patients to be maintained on recommended RAASi dose for cardio-renal benefits; further prospective studies are warranted to evaluate this.