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Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure
Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction. This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empaglifloz...
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| Published in: | Journal of the American College of Cardiology 2021-03, Vol.77 (11), p.1397-1407 |
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| container_title | Journal of the American College of Cardiology |
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| creator | Ferreira, João Pedro Zannad, Faiez Pocock, Stuart J. Anker, Stefan D. Butler, Javed Filippatos, Gerasimos Brueckmann, Martina Jamal, Waheed Steubl, Dominik Schueler, Elke Packer, Milton |
| description | Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.
This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
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| doi_str_mv | 10.1016/j.jacc.2021.01.044 |
| format | article |
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This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
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This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
[Display omitted]</description><subject>Cardiology and cardiovascular system</subject><subject>empagliflozin</subject><subject>heart failure</subject><subject>Human health and pathology</subject><subject>Life Sciences</subject><subject>mineralocorticoid receptor antagonists</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kM1Kw0AUhQdRbK2-gKtsXSTOTzIzATeltLZQEURxOUwmd-qENBMmUahP47P4ZCZUXAoHLlzOd7nnIHRNcEIw4bdVUmljEoopSfCgND1BU5JlMmZZLk7RFAuWxQTnYoIuuq7CGHNJ8nM0YUwwLimZotdN00Noa32IvI0eXANB19740DvjXRk9gYG29yGaN73e-cZ1fRfppoyW-1bvamdr_-maaNAadOi_v1ba1e8BLtGZ1XUHV79zhl5Wy-fFOt4-3m8W821smEj7mILhdvjFFAIYEVjoPDeU5yWkBZcMY8oLSTEIkjNmU16KTFgopLGmGIJZNkM3x7tvulZtcHsdDsprp9bzrRp3mBGZScE-yOClR68JvusC2D-AYDU2qio1NqrGRhUelKYDdHeEYEjx4SCozjhoDJQugOlV6d1_-A-dkX4x</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Ferreira, João Pedro</creator><creator>Zannad, Faiez</creator><creator>Pocock, Stuart J.</creator><creator>Anker, Stefan D.</creator><creator>Butler, Javed</creator><creator>Filippatos, Gerasimos</creator><creator>Brueckmann, Martina</creator><creator>Jamal, Waheed</creator><creator>Steubl, Dominik</creator><creator>Schueler, Elke</creator><creator>Packer, Milton</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-1828-2387</orcidid><orcidid>https://orcid.org/0000-0003-1215-0746</orcidid><orcidid>https://orcid.org/0000-0002-2304-6138</orcidid><orcidid>https://orcid.org/0000-0001-7456-1570</orcidid><orcidid>https://orcid.org/0000-0001-7683-4720</orcidid><orcidid>https://orcid.org/0000-0002-5640-0332</orcidid><orcidid>https://orcid.org/0000-0002-0805-8683</orcidid><orcidid>https://orcid.org/0000-0003-2212-4007</orcidid></search><sort><creationdate>202103</creationdate><title>Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure</title><author>Ferreira, João Pedro ; Zannad, Faiez ; Pocock, Stuart J. ; Anker, Stefan D. ; Butler, Javed ; Filippatos, Gerasimos ; Brueckmann, Martina ; Jamal, Waheed ; Steubl, Dominik ; Schueler, Elke ; Packer, Milton</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-2ec6f736cb7e31707a99c269de4b6830026b820e71933f46d757feb8cfcb109f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cardiology and cardiovascular system</topic><topic>empagliflozin</topic><topic>heart failure</topic><topic>Human health and pathology</topic><topic>Life Sciences</topic><topic>mineralocorticoid receptor antagonists</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferreira, João Pedro</creatorcontrib><creatorcontrib>Zannad, Faiez</creatorcontrib><creatorcontrib>Pocock, Stuart J.</creatorcontrib><creatorcontrib>Anker, Stefan D.</creatorcontrib><creatorcontrib>Butler, Javed</creatorcontrib><creatorcontrib>Filippatos, Gerasimos</creatorcontrib><creatorcontrib>Brueckmann, Martina</creatorcontrib><creatorcontrib>Jamal, Waheed</creatorcontrib><creatorcontrib>Steubl, Dominik</creatorcontrib><creatorcontrib>Schueler, Elke</creatorcontrib><creatorcontrib>Packer, Milton</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferreira, João Pedro</au><au>Zannad, Faiez</au><au>Pocock, Stuart J.</au><au>Anker, Stefan D.</au><au>Butler, Javed</au><au>Filippatos, Gerasimos</au><au>Brueckmann, Martina</au><au>Jamal, Waheed</au><au>Steubl, Dominik</au><au>Schueler, Elke</au><au>Packer, Milton</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure</atitle><jtitle>Journal of the American College of Cardiology</jtitle><date>2021-03</date><risdate>2021</risdate><volume>77</volume><issue>11</issue><spage>1397</spage><epage>1407</epage><pages>1397-1407</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><abstract>Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.
This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
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| subjects | Cardiology and cardiovascular system empagliflozin heart failure Human health and pathology Life Sciences mineralocorticoid receptor antagonists |
| title | Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure |
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