Evidence map›Insulin × cardiovascular events›PMID 25810334›Full record

SynthesisCirculation2015

Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.

Azmil H Abdul-Rahim, Ana-Cristina Perez, Rachael L Fulton, Pardeep S Jhund, Roberto Latini, Gianni Tognoni, John Wikstrand, John Kjekshus, Gregory Y H Lip, Aldo P Maggioni and 5 more

Registry-linked trialOpen access · bronzeAbstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Circulation, 2015. The graph read 5 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports 5 associations that do not count as treatment evidence, such as HR 1.81 (1.19 to 2.74) for stroke. It is linked to trial NCT04696120 (Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure), which is not on this map. Cited by 48 papers, 3 of them syntheses that pooled it.

5numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 3 pooled it
7.6field-weighted citation impact, top 2% of its field
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.

Read, but not usablea number the graph found but could not read as for or against

Strokeprevious stroke vs no previous stroke, in patients without AFan association or prognostic statement, not a treatment comparison · arrhythmia, t1dfeeds one cell of the map
HR 1.811.19 to 2.74
Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74).
FeedsInsulin×cardiovascular events
Strokebody mass index (per 5 kg/m(2) up to 30) vs reference BMI, in patients without AFan association or prognostic statement, not a treatment comparison · arrhythmia, t1dfeeds one cell of the map
HR 0.740.60 to 0.91
Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74).
FeedsInsulin×cardiovascular events
Strokeage (per 10 years) vs reference age, in patients without AFan association or prognostic statement, not a treatment comparison · arrhythmia, t1dfeeds one cell of the map
HR 1.341.18 to 1.63
Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74).
FeedsInsulin×cardiovascular events
StrokeNew York Heart Association class III/IV vs New York Heart Association class II, in patients without AFan association or prognostic statement, not a treatment comparison · arrhythmia, t1dfeeds one cell of the map
HR 1.601.21 to 2.12
Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74).
FeedsInsulin×cardiovascular events
Strokediabetes mellitus treated with insulin vs no diabetes or non-insulin treated diabetes, in patients without AFan association or prognostic statement, not a treatment comparison · arrhythmia, t1dfeeds one cell of the map
HR 1.871.22 to 2.88
Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74).
FeedsInsulin×cardiovascular events

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Insulin×cardiovascular events

No readable resultOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · head-to-head
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
Cardiovascular and Other Outcomes Postintervention With Insulin Glargi…PMID 26681720 · 2016
HR 1.010.94 to 1.10

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

NCT04696120 phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial

TypeinterventionalSponsorKorea University Guro HospitalRan2021 to 2023Enrolled200ConditionsHeart Failure, Sinus Rhythm, Cerebrovascular DiseaseArmsApixaban, Placebo
5 · Its place in the literature

Who cites it

48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Pooled it
  3. Marine-derived n-3 fatty acids therapy for stroke.The Cochrane database of systematic reviews · 2019
    Pooled it
  4. Trial
  5. SESC heart failure · 2024
    Trial
  6. Trial
  7. Trial
  8. Trial
  9. Observational
  10. Article
  11. Article
  12. Heart Failure and Stroke: A Narrative Review.Journal of clinical medicine · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

15 authors at 7 institutions in 5 countries.

Azmil H Abdul-RahimFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Ana-Cristina PerezFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Rachael L FultonFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Pardeep S JhundFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Roberto LatiniFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Gianni TognoniFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
John WikstrandFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
John KjekshusFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Gregory Y H LipFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Aldo P MaggioniFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Luigi TavazziFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
Kennedy R LeesFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
John J V McMurrayFrom Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.). john.mcmurray@glasgow.ac.uk.
Investigators of the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA)
GISSI-Heart Failure (GISSI-HF) Committees and Investigators
University of Birmingham · GBOslo University Hospital · NOAalborg University · DKAssociazione Nazionale Medici Cardiologi Ospedalieri · ITBirmingham City Hospital · GBMario Negri Institute for Pharmacological Research · ITUniversity of Gothenburg · SE

Funding

Medical Research Council MR/N003403/1
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundOur aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). METHODS AND

resultsWe pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.

conclusionsA small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Indexed as

AdultAgedAged, 80 and overAtrial FibrillationBenzimidazolesBiomarkersBiphenyl CompoundsCardiovascular AgentsDiabetes Mellitus, Type 1Fatty Acids, Omega-3FemaleFluorobenzenesFollow-Up StudiesHeart FailureHumansHydroxymethylglutaryl-CoA Reductase InhibitorsBenzimidazolesBiomarkersBiphenyl CompoundscandesartanCardiovascular AgentsFatty Acids, Omega-3FluorobenzenesHydroxymethylglutaryl-CoA Reductase InhibitorsNatriuretic Peptide, BrainPeptide Fragmentspro-brain natriuretic peptide (1-76)PyrimidinesRosuvastatin CalciumSulfonamidesTetrazolesatrial fibrillationheart failurerisk factorssinus rhythmstrokeventricular ejection fraction

Identifiers

PMID25810334
OpenAlexW2038337299

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

Registered trials

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.