Evidence map›Paper›PMID 35029056›Full record

SynthesisESC heart failure2022

Robustness of outcomes in trials evaluating sodium-glucose co-transporter 2 inhibitors for heart failure.

Muhammad Shariq Usman, Muhammad Shahzeb Khan, Gregg C Fonarow, Stephen J Greene, Tim Friede, Muthiah Vaduganathan, Gerasimos Filippatos, Andrew J Stewart Coats, Stefan D Anker, Javed Butler

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in ESC heart failure, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Muhammad Shariq UsmanDepartment of Medicine, University of Mississippi, Jackson, MS, USA.
Muhammad Shahzeb KhanDivision of Cardiology, Duke University Medical Center, Durham, NC, USA.
Gregg C FonarowDivision of Cardiology, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
Stephen J GreeneDivision of Cardiology, Duke University Medical Center, Durham, NC, USA.
Tim FriedeDepartment of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
Muthiah VaduganathanBrigham and Women's Hospital Heart & Vascular Center, Boston, MA, USA.
Gerasimos FilippatosNational and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.
Andrew J Stewart CoatsDepartment of Cardiology, IRCCS San Raffaele Pisana, Rome, Italy.
Stefan D AnkerDepartment of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); DZHK (German Centre for Cardiovascular Research), partner site Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Javed ButlerDepartment of Medicine, University of Mississippi, Jackson, MS, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsRecent trials have evaluated sodium-glucose co-transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). METHODS AND

resultsFragility index is defined as the minimum number of patients that must be moved from the 'non-event' to the 'event' group to turn a statistically significant result to non-significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non-significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all-cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all-cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta-analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all-cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile.

conclusionImprovement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium-glucose co-transporter 2 inhibitor trials. In contrast, secondary endpoints of all-cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events.

Indexed as

Heart FailureSodium-Glucose Transporter 2 InhibitorsSymportersGlucoseHumansSodiumGlucoseSodiumSodium-Glucose Transporter 2 InhibitorsSymportersCardiac failureFragility indexRobustnessSodium-glucose co-transporter 2 inhibitors

Identifiers

PMID35029056
PMCPMC8934993

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.