Efficacy and Safety of Dapagliflozin According to Frailty in Patients With Heart Failure: A Prespecified Analysis of the DELIVER Trial

被引：90

作者：

Butt, Jawad H. ^{[1
,2
]}

Jhund, Pardeep S. ^{[1
]}

Belohlavek, Jan ^{[3
]}

de Boer, Rudolf A. ^{[4
]}

Chiang, Chern-En ^{[5
,6
,7
]}

Desai, Akshai S. ^{[8
]}

Drozdz, Jaroslaw ^{[9
]}

Hernandez, Adrian F. ^{[10
]}

Inzucchi, Silvio E. ^{[11
]}

Katova, Tzvetana ^{[12
]}

Kitakaze, Masafumi ^{[13
]}

Kosiborod, Mikhail N. ^{[14
]}

Lam, Carolyn S. P. ^{[15
,16
]}

Langkilde, Anna Maria ^{[17
]}

Lindholm, Daniel ^{[17
]}

Bachus, Erasmus ^{[17
]}

Martinez, Felipe ^{[18
]}

Merkely, Bela ^{[19
]}

Petersson, Magnus ^{[17
]}

Saraiva, Jose F. Kerr ^{[20
]}

Shah, Sanjiv J. ^{[21
]}

Vaduganathan, Muthiah ^{[22
]}

Vardeny, Orly ^{[23
]}

Wilderang, Ulrica ^{[17
]}

Claggett, Brian C. ^{[22
]}

Solomon, Scott D. ^{[22
]}

McMurray, John J., V ^{[1
]}

机构：

[1] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland

[2] Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark

[3] Charles Univ Prague, Gen Teaching Hosp, Fac Med 1, Dept Internal Med 2,Cardiovasc Med, Prague, Czech Republic

[4] Erasmus MC, Rotterdam, Netherlands

[5] Taipei Vet Gen Hosp, Gen Clin Res Ctr, Taipei, Taiwan

[6] Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan

[7] Natl Yang Ming Chiao Tung Univ, Taipei, Taiwan

[8] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

[9] Med Univ Lodz, Dept Cardiol, Lodz, Poland

[10] Duke Univ, Med Ctr, Durham, NC USA

[11] Yale Sch Med, New Haven, CT USA

[12] Natl Cardiol Hosp, Dept Noninvas Cardiol, Sofia, Bulgaria

[13] Natl Cerebral & Cardiovasc Ctr, Cardiovasc Div Med, Osaka, Japan

[14] St Lukes Mid Amer Heart Inst, Kansas City, MO USA

[15] Natl Heart Ctr Singapore, Singapore, Singapore

[16] Duke Natl Univ Singapore, Singapore, Singapore

[17] AstraZeneca, BioPharmaceut R&D, Late Stage Dev Cardiovasc Renal & Metab, Gothenburg, Sweden

[18] Univ Cordoba, Cordoba, Argentina

[19] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary

[20] Inst Pesquisa Clin Campinas, Cardiovasc Div, Campinas, Brazil

[21] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[22] Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA

[23] Univ Minnesota, Minneapolis VA Ctr Care Delivery & Outcomes Res, Minneapolis, MN 55455 USA

来源：

CIRCULATION | 2022年 / 146卷 / 16期

关键词：

clinical trial; dapagliflozin; frailty; heart failure; REDUCED EJECTION FRACTION; DEFICIT-ACCUMULATION; OLDER-ADULTS; INDEX; PREVALENCE; VALIDATION; DISABILITY; THERAPY; HEALTH;

D O I：

10.1161/CIRCULATIONAHA.122.061754

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). METHODS: Frailty was measured using the Rockwood cumulative deficit approach. The primary end point was time to a first worsening heart failure event or cardiovascular death. RESULTS: Of the 6263 patients randomized, a frailty index (FI) was calculable in 6258. In total, 2354 (37.6%) patients had class 1 frailty (FI <= 0.210; ie, not frail), 2413 (38.6%) had class 2 frailty (FI 0.211-0.310; ie, more frail), and 1491 (23.8%) had class 3 frailty (FI >= 0.311; ie, most frail). Greater frailty was associated with a higher rate of the primary end point (per 100 person-years): FI class 1, 6.3 (95% CI 5.7-7.1); class 2, 8.3 (7.5-9.1); and class 3, 13.4 (12.1-14.7; P<0.001). The effect of dapagliflozin (as a hazard ratio) on the primary end point from FI class 1 to 3 was 0.85 (95% CI, 0.68-1.06), 0.89 (0.74-1.08), and 0.74 (0.61-0.91), respectively (P-interaction=0.40). Although patients with a greater degree of frailty had worse Kansas City Cardiomyopathy Questionnaire scores at baseline, their improvement with dapagliflozin was greater than it was in patients with less frailty: placebo-corrected improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score at 4 months in FI class 1 was 0.3 (95% CI, -0.9 to 1.4); in class 2, 1.5 (0.3-2.7); and in class 3, 3.4 (1.7-5.1; P-interaction=0.021). Adverse reactions and treatment discontinuation, although more frequent in patients with a greater degree of frailty, were not more common with dapagliflozin than with placebo irrespective of frailty class. CONCLUSIONS: In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with a higher level of frailty.

引用

页码：1210 / 1224

页数：15

共 41 条

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