Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature
Abstract Aims Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end‐diastoli...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-06-01
|
| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.12681 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832544439950639104 |
|---|---|
| author | Navkaranbir S. Bajaj Kartik Gupta Nitin Gharpure Mike Pate Lakshay Chopra Rajat Kalra Sumanth D. Prabhu |
| author_facet | Navkaranbir S. Bajaj Kartik Gupta Nitin Gharpure Mike Pate Lakshay Chopra Rajat Kalra Sumanth D. Prabhu |
| author_sort | Navkaranbir S. Bajaj |
| collection | DOAJ |
| description | Abstract Aims Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end‐diastolic dimension (LVEDD), and all‐cause mortality in patients with HF with reduced ejection fraction (HFrEF) through meta‐analyses and trial sequential analyses (TSAs) of RCTs. Methods and results PubMed, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov were systematically reviewed to identify RCTs that studied the effects of immunomodulation in patients with HFrEF. The primary endpoint in this analysis was change in LVEF. Secondary outcomes were changes in LVEDD and all‐cause mortality. TSA was used to quantify the statistical reliability of data in the cumulative meta‐analyses. Nineteen RCTs with 1341 HFrEF subjects were eligible for analyses. The aetiology of HF, specific immunomodulation strategy, and treatment duration were variable across trials. Immunomodulation led to a greater improvement in LVEF [mean difference: +5.7% 95% confidence interval (CI): 3.0–8.5%, P < 0.001] and reduction in LVEDD (mean difference: −3.7 mm, 95% CI: −7.0 to −0.4 mm, P = 0.028) than no immunomodulation in meta‐analyses and TSAs. We observed a non‐significant decrease in all‐cause mortality among those on immumomodulation (risk ratio: 0.7, 95% CI: 0.4–1.3, P = 0.234), but the Z‐curve for cumulative treatment effect of immunomodulation in the TSA did not cross the boundary of futility. Conclusions Immunomodulation led to improved cardiac structure and function in patients with HFrEF. While these benefits did not translate into a significant improvement in mortality, our analysis suggests that larger studies of targeted immunomodulation are needed to understand the true benefits. |
| format | Article |
| id | doaj-art-db04d5416bf941abb00babca3991ae42 |
| institution | Kabale University |
| issn | 2055-5822 |
| language | English |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-db04d5416bf941abb00babca3991ae422025-02-03T10:25:46ZengWileyESC Heart Failure2055-58222020-06-01731319133010.1002/ehf2.12681Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literatureNavkaranbir S. Bajaj0Kartik Gupta1Nitin Gharpure2Mike Pate3Lakshay Chopra4Rajat Kalra5Sumanth D. Prabhu6Division of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USADivision of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USADivision of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USADivision of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USADivision of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USACardiovascular Division University of Minnesota Minneapolis MN USADivision of Cardiovascular Disease University of Alabama at Birmingham 1900 University Boulevard, 311 THT Birmingham AL 35294‐0006 USAAbstract Aims Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end‐diastolic dimension (LVEDD), and all‐cause mortality in patients with HF with reduced ejection fraction (HFrEF) through meta‐analyses and trial sequential analyses (TSAs) of RCTs. Methods and results PubMed, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov were systematically reviewed to identify RCTs that studied the effects of immunomodulation in patients with HFrEF. The primary endpoint in this analysis was change in LVEF. Secondary outcomes were changes in LVEDD and all‐cause mortality. TSA was used to quantify the statistical reliability of data in the cumulative meta‐analyses. Nineteen RCTs with 1341 HFrEF subjects were eligible for analyses. The aetiology of HF, specific immunomodulation strategy, and treatment duration were variable across trials. Immunomodulation led to a greater improvement in LVEF [mean difference: +5.7% 95% confidence interval (CI): 3.0–8.5%, P < 0.001] and reduction in LVEDD (mean difference: −3.7 mm, 95% CI: −7.0 to −0.4 mm, P = 0.028) than no immunomodulation in meta‐analyses and TSAs. We observed a non‐significant decrease in all‐cause mortality among those on immumomodulation (risk ratio: 0.7, 95% CI: 0.4–1.3, P = 0.234), but the Z‐curve for cumulative treatment effect of immunomodulation in the TSA did not cross the boundary of futility. Conclusions Immunomodulation led to improved cardiac structure and function in patients with HFrEF. While these benefits did not translate into a significant improvement in mortality, our analysis suggests that larger studies of targeted immunomodulation are needed to understand the true benefits.https://doi.org/10.1002/ehf2.12681Heart failureInflammationImmunomodulationLeft ventricular ejection fractionAnti‐cytokine therapy |
| spellingShingle | Navkaranbir S. Bajaj Kartik Gupta Nitin Gharpure Mike Pate Lakshay Chopra Rajat Kalra Sumanth D. Prabhu Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature ESC Heart Failure Heart failure Inflammation Immunomodulation Left ventricular ejection fraction Anti‐cytokine therapy |
| title | Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature |
| title_full | Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature |
| title_fullStr | Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature |
| title_full_unstemmed | Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature |
| title_short | Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature |
| title_sort | effect of immunomodulation on cardiac remodelling and outcomes in heart failure a quantitative synthesis of the literature |
| topic | Heart failure Inflammation Immunomodulation Left ventricular ejection fraction Anti‐cytokine therapy |
| url | https://doi.org/10.1002/ehf2.12681 |
| work_keys_str_mv | AT navkaranbirsbajaj effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT kartikgupta effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT nitingharpure effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT mikepate effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT lakshaychopra effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT rajatkalra effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature AT sumanthdprabhu effectofimmunomodulationoncardiacremodellingandoutcomesinheartfailureaquantitativesynthesisoftheliterature |