Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protocol Registration
2.2. Data Sources and Search Strategy
2.3. Eligibility Criteria and Study Selection
2.4. Study Selection
2.5. Data Extraction
2.6. Risk of Bias and Certainty of Evidence
2.7. Statistical Analysis
3. Results
3.1. Search Results and Study Selection
3.2. Characteristics of the Included Studies
3.3. Risk of Bias and Certainty of Evidence
3.4. Echocardiographic Parameters
3.5. Hemodynamic Parameters
3.6. Clinical Parameters
3.7. Safety Outcomes
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACA/AHA | American College of Cardiology/American Heart Association |
AF | Atrial fibrillation |
AHF | Acute heart failure |
BMI | Body mass index |
bpm | Beats per minute |
CABG | Coronary artery bypass graft |
CI | Confidence interval |
CKD | Chronic kidney disease |
CS | Cardiogenic shock |
DIG | Digitalis Investigation Group |
DBP | Diastolic blood pressure |
df | Degrees of freedom |
DM | Diabetes mellitus |
EC | Excitation–contraction |
ESC | European Society of Cardiology |
HFrEF | Heart failure with reduced ejection fraction |
HR | Heart rate |
HTN | Hypertension |
I | Istaroxime |
IVC | Inferior vena cava |
ID | Identification |
L | Liter |
LV | Left ventricle |
LVEDV | Left ventricular end-diastolic volume |
LVEF | Left ventricular ejection fraction |
LVESV | Left ventricular end-systolic volume |
M | Mean |
MAP | Mean arterial pressure |
MD | Mean difference |
N | Number |
NCX | Na+/Ca+2 exchange |
p | Probability |
PICO | Population Intervention Comparison Outcomes |
Pl | Placebo |
PCI | Percutaneous coronary intervention |
PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
RCT | Randomized controlled trial |
SBP | Systolic blood pressure |
SCAI | Society of Cardiovascular Angiography and Interventions |
SD | Standard deviation |
SERCA2a | Sarcoplasmic reticulum Ca+2 adenosine triphosphatase isoform 2a |
US | United States |
. (period) | Missing data. |
References
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Study ID | Study Design | Country | Total Participants | Istaroxime | Primary Outcome | |
---|---|---|---|---|---|---|
Dosage | Treatment Duration | |||||
Carubelli et al., 2020 [20] | Double-blinded multicenter phase II RCT | Italy and China | 120 | 0.5 μg/kg/min (cohort 1), 1.0 μg/kg/min in (cohort 2) | 24 h | E/e′ ratio change |
Metra et al., 2022 [19] (SEISMiC) | Double-blinded multicenter phase II RCT | US, Italy, Russia, Romania, and Poland | 60 | 1.0–1.5 μg/kg/min | 24 h | SBP change |
Shah et al., 2009 [21] (HORIZON-HF) | Double-blinded multicenter RCT | US, Italy, Greece, Romania, and Poland | 120 | 0.5, 1.0, or 1.5 μg/kg/min | 6 h | Pulmonary capillary wedge pressure change |
Study ID | Number of Patients in Each Group | Age (Years) Mean (SD) | Gender (Male) N (%) | BMI Mean (SD) | SBP Mean (SD) | DBP Mean (SD) | HR Mean (SD) | Comorbidities N (%) | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
I | Pl | I | Pl | I | Pl | I | Pl | I | Pl | I | Pl | I | Pl | AF | HTN | PCI | CABG | DM | CKD | |||||||
I | Pl | I | Pl | I | Pl | I | Pl | I | Pl | I | Pl | |||||||||||||||
Carubelli et al., 2020 Cohort 1) [20] | 41 | 19 | 60 (16) | 58 (17) | 34 (83) | 16 (84) | 25 (4) | 25 (3) | 105 (12) | 105 (8) | . | . | 72 (13) | 77 (17) | 8 (20) | 5 (26) | 17 (42) | 11 (58) | . | . | . | . | 14 (34) | 5 (26) | 12 (29) | 5 (26) |
Carubelli et al., 2020 Cohort 2) [20] | 40 | 20 | 52 (13) | 56 (16) | 34 (85) | 18 (90) | 23 (4) | 24 (4) | 106 (10) | 108 (10) | . | . | 78 (11) | 79 (13) | 11 (28) | 6 (30) | 14 (35) | 7 (35) | . | . | . | . | 6 (15) | 4 (20) | 10 (24) | 6 (30) |
Metra et al., 2022 [19] (SEISMiC) | 29 | 31 | 65 (10) | 63 (13) | 22 (76) | 27 (87) | 28 (6) | 27 (6) | 88 (3) | 87 (3) | . | . | 84 (16) | 84 (19) | 16 (55) | 18 (58) | 25 (86) | 23 (74) | 9 (31) | 17 (55) | 4 (14) | 3 (10) | 9 (31) | 14 (45) | 2 (7) | 2 (6) |
Shah et al., 2009 [21] (HORIZON-HF) | 89 | 31 | 55 (11) | 57 (10) | 80 (90) | 25 (81) | . | . | 117 (12) | 114 (15) | 70 (7) | 70 (8) | 74 (9) | 72 (11) | . | . | . | . | 20 (22) | 10 (32) | 4 (4) | 4 (13) | 16 (18) | 5 (16) | . | . |
Certainty Assessment | Summary of Findings | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Participants (Studies) Follow-up | Risk of Bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Overall Certainty of Evidence | Study Event Rates (%) | Relative Effect (95% CI) | Anticipated Absolute Effects | ||
With [Placebo] | With [Istaroxime] | Risk with [Placebo] | Risk Difference with [Istaroxime] | ||||||||
Echo-LV end-diastolic volume | |||||||||||
288 (4 RCTs) | not serious | very serious a | not serious | very serious b | none | ⨁◯◯◯ Very low | 99 | 189 | - | The mean echo-LV end-diastolic volume was 0 | MD 4.69 lower (12.85 lower to 3.48 higher) |
Echo-LV end-systolic volume | |||||||||||
288 (4 RCTs) | not serious | very serious a | not serious | very serious b | none | ⨁◯◯◯ Very low | 99 | 189 | - | The mean echo-LV end-systolic volume was 0 | MD 5.4 lower (12.05 lower to 1.25 higher) |
Echo-LV ejection fraction | |||||||||||
288 (4 RCTs) | not serious | not serious | not serious | Serious b | none | ⨁⨁⨁◯ Moderate | 99 | 189 | - | The mean echo-LV ejection fraction was 0 | MD 1.06 higher (0.29 higher to 1.82 higher) |
Echo-stroke volume index | |||||||||||
284 (4 RCTs) | not serious | not serious | not serious | not serious | none | ⨁⨁⨁⨁ High | 98 | 186 | - | The mean echo-stroke volume index was 0 | MD 3.04 higher (2.41 higher to 3.67 higher) |
Echo-cardiac index change (L/min/m2) | |||||||||||
300 (4 RCTs) | not serious | not serious | not serious | not serious | none | ⨁⨁⨁⨁ High | 101 | 199 | - | The mean echo- cardiac index change (L/min/m2) was 0 | MD 0.18 higher (0.11 higher to 0.25 higher) |
Echo-E/A ratio | |||||||||||
239 (4 RCTs) | not serious | not serious | not serious | not serious | none | ⨁⨁⨁⨁ High | 83 | 156 | - | The mean echo-E/A ratio was 0 | MD 0.39 lower (0.58 lower to 0.19 lower) |
Echo-E/e′ ratio | |||||||||||
165 (3 RCTs) | not serious | very serious a | not serious | very serious b | none | ⨁◯◯◯ Very low | 66 | 99 | - | The mean echo-E/e′ ratio was 0 | MD 1.04 lower (4.15 lower to 2.07 higher) |
Echo-IVC diameter | |||||||||||
180 (3 RCTs) | not serious | very serious a | not serious | very serious b | none | ⨁◯◯◯ Very low | 70 | 110 | - | The mean echo-IVC diameter was 0 | MD 1.82 lower (3.74 lower to 0.1 higher) |
Echo-pulmonary artery systolic pressure | |||||||||||
180 (3 RCTs) | not serious | not serious | not serious | Serious b | none | ⨁⨁⨁◯ Moderate | 70 | 110 | - | The mean echo- pulmonary artery systolic pressure was 0 | MD 2.3 lower (3.2 lower to 1.4 lower) |
Hemodynamic-SBP | |||||||||||
300 (4 RCTs) | not serious | not serious | not serious | Serious b | none | ⨁⨁⨁◯ Moderate | 101 | 199 | - | The mean hemodynamic outcomes-SBP was 0 | MD 5.32 higher (2.28 higher to 8.37 higher) |
Hemodynamic-MAP | |||||||||||
180 (2 RCTs) | not serious | not serious | not serious | Serious b | none | ⨁⨁⨁◯ Moderate | 62 | 118 | - | The mean hemodynamic outcomes-MAP was 0 | MD 2.44 higher (0.17 lower to 5.05 higher) |
Hemodynamic-HR | |||||||||||
300 (4 RCTs) | not serious | not serious | not serious | Serious b | none | ⨁⨁⨁◯ Moderate | 101 | 199 | - | The mean hemodynamic outcomes-HR change was 0 | MD 3.05 lower (5.27 lower to 0.82 lower) |
Clinical-NT-proBNP change | |||||||||||
180 (3 RCTs) | not serious | not serious | not serious | very serious b | strong association | ⨁⨁⨁◯ Moderate | 70 | 110 | - | The mean clinical outcomes-NT-proBNP change was 0 | MD 808.28 higher (523.98 higher to 1092.58 higher) |
Clinical-length of hospital stay | |||||||||||
180 (3 RCTs) | not serious | not serious | not serious | not serious | none | ⨁⨁⨁⨁ High | 70 | 110 | - | The mean clinical outcomes-length of stay was 0 | MD 0.23 lower (1.66 lower to 1.21 higher) |
Clinical-worsening HF | |||||||||||
180 (3 RCTs) | not serious | not serious | not serious | very serious b | none | ⨁⨁◯◯ Low | 3/70 (4.3%) | 9/110 (8.2%) | RR 2.13 (0.64 to 7.05) | 43 per 1000 | 48 more per 1000 (from 15 fewer to 259 more) |
Clinical-hospital readmission | |||||||||||
180 (3 RCTs) | not serious | not serious | not serious | very serious b | none | ⨁⨁◯◯ Low | 5/70 (7.1%) | 8/110 (7.3%) | RR 0.94 (0.30 to 2.99) | 71 per 1000 | 4 fewer per 1000 (from 50 fewer to 142 more) |
Safety-any adverse event | |||||||||||
180 (2 RCTs) | not serious | not serious | not serious | very serious b | none | ⨁⨁◯◯ Low | 48/70 (68.6%) | 91/110 (82.7%) | RR 1.26 (1.05 to 1.51) | 686 per 1000 | 178 more per 1000 (from 34 more to 350 more) |
Safety-any serious adverse event | |||||||||||
180 (2 RCTs) | not serious | not serious | not serious | very serious b | none | ⨁⨁◯◯ Low | 8/70 (11.4%) | 14/110 (12.7%) | RR 1.34 (0.58 to 3.11) | 114 per 1000 | 39 more per 1000 (from 48 fewer to 241 more) |
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Abuelazm, M.; Ali, S.; AlBarakat, M.M.; Mahmoud, A.; Tanashat, M.; Suilik, H.A.; Abdelazeem, B.; Brašić, J.R. Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diseases 2023, 11, 183. https://doi.org/10.3390/diseases11040183
Abuelazm M, Ali S, AlBarakat MM, Mahmoud A, Tanashat M, Suilik HA, Abdelazeem B, Brašić JR. Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diseases. 2023; 11(4):183. https://doi.org/10.3390/diseases11040183
Chicago/Turabian StyleAbuelazm, Mohamed, Shafaqat Ali, Majd M. AlBarakat, Abdelrahman Mahmoud, Mohammad Tanashat, Husam Abu Suilik, Basel Abdelazeem, and James Robert Brašić. 2023. "Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials" Diseases 11, no. 4: 183. https://doi.org/10.3390/diseases11040183
APA StyleAbuelazm, M., Ali, S., AlBarakat, M. M., Mahmoud, A., Tanashat, M., Suilik, H. A., Abdelazeem, B., & Brašić, J. R. (2023). Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diseases, 11(4), 183. https://doi.org/10.3390/diseases11040183