Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design

Gianluigi Savarese; Camilla Settergren; Benedikt Schrage; Tonje Thorvaldsen; Ida Löfman; Ulrik Sartipy; Linda Mellbin; Andrea Meyers; Soulmaz Fazeli Farsani; Martina Brueckmann; Kimberly G Brodovicz; Ola Vedin; Folkert W Asselbergs; Ulf Dahlström; Francesco Cosentino; Lars H Lund

doi:10.1016/j.ijcard.2020.04.068

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design

Standard

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design. / Savarese, Gianluigi; Settergren, Camilla; Schrage, Benedikt; Thorvaldsen, Tonje; Löfman, Ida; Sartipy, Ulrik; Mellbin, Linda; Meyers, Andrea; Farsani, Soulmaz Fazeli; Brueckmann, Martina; Brodovicz, Kimberly G; Vedin, Ola; Asselbergs, Folkert W; Dahlström, Ulf; Cosentino, Francesco; Lund, Lars H.

In: INT J CARDIOL, Vol. 313, 15.08.2020, p. 76-82.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Savarese, G, Settergren, C, Schrage, B, Thorvaldsen, T, Löfman, I, Sartipy, U, Mellbin, L, Meyers, A, Farsani, SF, Brueckmann, M, Brodovicz, KG, Vedin, O, Asselbergs, FW, Dahlström, U, Cosentino, F & Lund, LH 2020, 'Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design', INT J CARDIOL, vol. 313, pp. 76-82. https://doi.org/10.1016/j.ijcard.2020.04.068

APA

Savarese, G., Settergren, C., Schrage, B., Thorvaldsen, T., Löfman, I., Sartipy, U., Mellbin, L., Meyers, A., Farsani, S. F., Brueckmann, M., Brodovicz, K. G., Vedin, O., Asselbergs, F. W., Dahlström, U., Cosentino, F., & Lund, L. H. (2020). Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design. INT J CARDIOL, 313, 76-82. https://doi.org/10.1016/j.ijcard.2020.04.068

Vancouver

Savarese G, Settergren C, Schrage B, Thorvaldsen T, Löfman I, Sartipy U et al. Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design. INT J CARDIOL. 2020 Aug 15;313:76-82. https://doi.org/10.1016/j.ijcard.2020.04.068

Bibtex

@article{e1fef96f9e544bbeb5b635e30f5dd5aa,

title = "Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design",

abstract = "BACKGROUND: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.METHODS AND RESULTS: Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.CONCLUSION: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.",

keywords = "Clinical Trials as Topic, Diabetes Mellitus, Type 2/diagnosis, Heart Failure/diagnosis, Humans, Prognosis, Stroke Volume, Sweden",

author = "Gianluigi Savarese and Camilla Settergren and Benedikt Schrage and Tonje Thorvaldsen and Ida L{\"o}fman and Ulrik Sartipy and Linda Mellbin and Andrea Meyers and Farsani, {Soulmaz Fazeli} and Martina Brueckmann and Brodovicz, {Kimberly G} and Ola Vedin and Asselbergs, {Folkert W} and Ulf Dahlstr{\"o}m and Francesco Cosentino and Lund, {Lars H}",

year = "2020",

month = aug,

day = "15",

doi = "10.1016/j.ijcard.2020.04.068",

language = "English",

volume = "313",

pages = "76--82",

journal = "INT J CARDIOL",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design

AU - Savarese, Gianluigi

AU - Settergren, Camilla

AU - Schrage, Benedikt

AU - Thorvaldsen, Tonje

AU - Löfman, Ida

AU - Sartipy, Ulrik

AU - Mellbin, Linda

AU - Meyers, Andrea

AU - Farsani, Soulmaz Fazeli

AU - Brueckmann, Martina

AU - Brodovicz, Kimberly G

AU - Vedin, Ola

AU - Asselbergs, Folkert W

AU - Dahlström, Ulf

AU - Cosentino, Francesco

AU - Lund, Lars H

PY - 2020/8/15

Y1 - 2020/8/15

N2 - BACKGROUND: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.METHODS AND RESULTS: Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.CONCLUSION: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

AB - BACKGROUND: Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.METHODS AND RESULTS: Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.CONCLUSION: HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

KW - Clinical Trials as Topic

KW - Diabetes Mellitus, Type 2/diagnosis

KW - Heart Failure/diagnosis

KW - Humans

KW - Prognosis

KW - Stroke Volume

KW - Sweden

U2 - 10.1016/j.ijcard.2020.04.068

DO - 10.1016/j.ijcard.2020.04.068

M3 - SCORING: Journal article

C2 - 32360702

VL - 313

SP - 76

EP - 82

JO - INT J CARDIOL

JF - INT J CARDIOL

SN - 0167-5273

ER -