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Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF

Session Mechanisms of Heart Failure and Implications for Clinical Translation

Speaker Soeren Lund Kristensen

Event : ESC Congress 2020

  • Topic : heart failure
  • Sub-topic : Heart Failure with Reduced Ejection Fraction (HFrEF)
  • Session type : Rapid Fire Abstracts

Authors : SL Kristensen (Copenhagen,DK), KF Docherty (Glasgow,GB), PS Jhund (Glasgow,GB), O Bengtsson (Gothenburg,SE), DL Demets (Madison,US), SE Inzucchi (New Haven,US), L Kober (Copenhagen,DK), MN Kosiborod (Kansas City,US), AM Langkilde (Gothenburg,SE), FA Martinez (Cordoba,AR), P Ponikowski (Wroclaw,PL), MS Sabatine (Boston,US), M Sjostrand (Gothenburg,SE), SD Solomon (Boston,US), JJV Mcmurray (Glasgow,GB)

Authors:
SL Kristensen1 , KF Docherty2 , PS Jhund2 , O Bengtsson3 , DL Demets4 , SE Inzucchi5 , L Kober1 , MN Kosiborod6 , AM Langkilde3 , FA Martinez7 , P Ponikowski8 , MS Sabatine9 , M Sjostrand3 , SD Solomon9 , JJV Mcmurray2 , 1Rigshospitalet - Copenhagen University Hospital - Copenhagen - Denmark , 2University of Glasgow - Glasgow - United Kingdom of Great Britain & Northern Ireland , 3AstraZeneca - Gothenburg - Sweden , 4University of Wisconsin-Madison - Madison - United States of America , 5Yale University - New Haven - United States of America , 6St. Luke's Mid America Heart Institute - Kansas City - United States of America , 7National University of Cordoba - Cordoba - Argentina , 8Wroclaw Medical University - Wroclaw - Poland , 9Brigham And Women'S Hospital, Harvard Medical School - Boston - United States of America ,

Topic(s):
Heart Failure with Reduced Ejection Fraction

Background: Hyperkalaemia often limits the use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF), denying these patients a life-saving therapy.

Purpose: To determine whether treatment with the sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin reduces the risk of hyperkalaemia associated with MRA use in patients with HFrEF.

Methods: The risk of developing mild hyperkalaemia (potassium > 5.5 mmol/L) and moderate/severe hyperkalaemia (>6.0 mmol/L) was examined in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) according to background MRA use, and randomized treatment assignment, by use of Cox regression analyses.

Results: Overall, 3370 (70.1%) patients in DAPA-HF were treated with an MRA. Mild hyperkalaemia and moderate/severe hyperkalaemia occurred in 182 (11.1%) and 23 (1.4%) patients treated with dapagliflozin as compared to 204 (12.6%) and 40 (2.4%) of patients given placebo (Table and Figure). This yielded a hazard ratio (HR) of 0.86 (0.70-1.05) for mild hyperkalaemia and 0.50 (0.29, 0.85) for moderate/severe hyperkalaemia, comparing dapagliflozin to placebo.

Conclusions: Patients with HFrEF and taking a MRA who were randomized to dapagliflozin had half the incidence of moderate/severe hyperkalaemia, compared with those randomized to placebo.

Dapagliflozin Placebo
No. events/patients

Rate

per 100py

No. events/patients

Rate

per 100py

HR

(95% CI)

P-value

Mild hyperkalaemia

(>5.5 mmol/L)*

No MRA at baseline 63/661 7.1 58/684 6.5

1.20

(0.84-1.72)

0.32
MRA treated at baseline 182/1637 8.6 204/1626 9.8

0.86

(0.70-1.05)

0.14
All patients 245/2298 8.2 262/2310 8.8

0.93

(0.78-1.11)

0.42

Moderate/Severe hyperkalaemia

(>6.0 mmol/L)**

No MRA at baseline 13/676 1.4 11/697 1.1

1.17

(0.52-2.62)

0.71
MRA treated at baseline 23/1688 1.0 40/1667 1.7

0.50

(0.29-0.85)

0.010
All patients 36/2364 1.1 51/2364 1.6

0.64

(0.42-0.99)

0.046
Models adjusted for baseline potassium and stratified by diabetes status at randomization. * Excluding those with baseline K+ >5.5 (n=136) ** Excluding those with baseline K+ >6.0 (n=16) Abbreviations: CI, confidence interval; HR, hazard ratio; MRA, mineralocorticoid receptor antagonist; PY, patient-years.

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