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Real-world dosing of renin-angiotensin-aldosterone system inhibitors in heart failure patients, and associations between hyperkalaemia and down-titration or discontinuation

Session Poster Session 6

Speaker Professor Cecilia Linde

Event : ESC Congress 2018

  • Topic : heart failure
  • Sub-topic : Epidemiology, Prognosis, Outcome
  • Session type : Poster Session

Authors : C Linde (Stockholm,SE), P Mcewan (Cardiff,GB), A Bakhai (London,GB), H Furuland (Uppsala,SE), M Evans (Cardiff,GB), D Ayoubkhani (Cardiff,GB), S Grandy (Gaithersburg,US), E Palaka (Cambridge,GB), L Qin (Gaithersburg,US)

C. Linde1 , P. McEwan2 , A. Bakhai3 , H. Furuland4 , M. Evans5 , D. Ayoubkhani2 , S. Grandy6 , E. Palaka7 , L. Qin6 , 1Karolinska University Hospital, Heart and Vascular Theme - Stockholm - Sweden , 2Health Economics and Outcomes Research Ltd - Cardiff - United Kingdom , 3Royal Free Hospital, Department of Cardiology - London - United Kingdom , 4Uppsala University Hospital, Department of Nephrology - Uppsala - Sweden , 5University Hospital Llandough, Diabetes Resource Centre - Cardiff - United Kingdom , 6AstraZeneca, Global Health Economics - Gaithersburg - United States of America , 7AstraZeneca, Global Health Economics - Cambridge - United Kingdom ,

Chronic Heart Failure – Epidemiology, Prognosis, Outcome

European Heart Journal ( 2018 ) 39 ( Supplement ), 1194

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.

Figure 1

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