Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study

Peter Nørkjær Laursen*, Lene Holmvang, Jacob Lønborg, Lars Køber, Dan E. Høfsten, Steffen Helqvist, Peter Clemmensen, Henning Kelbæk, Erik Jørgensen, Jens Flensted Lassen, Frants Pedersen, Thomas Høi-Hansen, Christian Juhl Therkelsen, Hans Henrik Tilsted, Lisette Okkels Jensen, Lars Nepper-Christensen, Golnaz Sadjadieh, Thomas Engstrøm

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.

OriginalsprogEngelsk
TidsskriftAmerican Heart Journal
Vol/bind204
Sider (fra-til)128-138
ISSN0002-8703
DOI
StatusUdgivet - 1. okt. 2018

Fingeraftryk

Randomized Controlled Trials
Denmark
Population
Registries
Cohort Studies

Citer dette

Laursen, Peter Nørkjær ; Holmvang, Lene ; Lønborg, Jacob ; Køber, Lars ; Høfsten, Dan E. ; Helqvist, Steffen ; Clemmensen, Peter ; Kelbæk, Henning ; Jørgensen, Erik ; Lassen, Jens Flensted ; Pedersen, Frants ; Høi-Hansen, Thomas ; Therkelsen, Christian Juhl ; Tilsted, Hans Henrik ; Jensen, Lisette Okkels ; Nepper-Christensen, Lars ; Sadjadieh, Golnaz ; Engstrøm, Thomas. / Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study. I: American Heart Journal. 2018 ; Bind 204. s. 128-138.
@article{0c5b7658c8b34698b3c75679bea70df0,
title = "Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study",
abstract = "Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30{\%}) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70{\%}) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95{\%} CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.",
keywords = "Aged, Angina, Stable/surgery, Angina, Unstable/surgery, Cause of Death, Denmark, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction/mortality, Myocardial Ischemia/mortality, Patient Readmission, Patient Selection, Percutaneous Coronary Intervention, Randomized Controlled Trials as Topic, ST Elevation Myocardial Infarction/mortality",
author = "Laursen, {Peter N{\o}rkj{\ae}r} and Lene Holmvang and Jacob L{\o}nborg and Lars K{\o}ber and H{\o}fsten, {Dan E.} and Steffen Helqvist and Peter Clemmensen and Henning Kelb{\ae}k and Erik J{\o}rgensen and Lassen, {Jens Flensted} and Frants Pedersen and Thomas H{\o}i-Hansen and Therkelsen, {Christian Juhl} and Tilsted, {Hans Henrik} and Jensen, {Lisette Okkels} and Lars Nepper-Christensen and Golnaz Sadjadieh and Thomas Engstr{\o}m",
year = "2018",
month = "10",
day = "1",
doi = "10.1016/j.ahj.2018.05.018",
language = "English",
volume = "204",
pages = "128--138",
journal = "American Heart Journal",
issn = "0002-8703",
publisher = "Mosby, Inc.",

}

Laursen, PN, Holmvang, L, Lønborg, J, Køber, L, Høfsten, DE, Helqvist, S, Clemmensen, P, Kelbæk, H, Jørgensen, E, Lassen, JF, Pedersen, F, Høi-Hansen, T, Therkelsen, CJ, Tilsted, HH, Jensen, LO, Nepper-Christensen, L, Sadjadieh, G & Engstrøm, T 2018, 'Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study', American Heart Journal, bind 204, s. 128-138. https://doi.org/10.1016/j.ahj.2018.05.018

Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study. / Laursen, Peter Nørkjær; Holmvang, Lene; Lønborg, Jacob; Køber, Lars; Høfsten, Dan E.; Helqvist, Steffen; Clemmensen, Peter; Kelbæk, Henning; Jørgensen, Erik; Lassen, Jens Flensted; Pedersen, Frants; Høi-Hansen, Thomas; Therkelsen, Christian Juhl; Tilsted, Hans Henrik; Jensen, Lisette Okkels; Nepper-Christensen, Lars; Sadjadieh, Golnaz; Engstrøm, Thomas.

I: American Heart Journal, Bind 204, 01.10.2018, s. 128-138.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study

AU - Laursen, Peter Nørkjær

AU - Holmvang, Lene

AU - Lønborg, Jacob

AU - Køber, Lars

AU - Høfsten, Dan E.

AU - Helqvist, Steffen

AU - Clemmensen, Peter

AU - Kelbæk, Henning

AU - Jørgensen, Erik

AU - Lassen, Jens Flensted

AU - Pedersen, Frants

AU - Høi-Hansen, Thomas

AU - Therkelsen, Christian Juhl

AU - Tilsted, Hans Henrik

AU - Jensen, Lisette Okkels

AU - Nepper-Christensen, Lars

AU - Sadjadieh, Golnaz

AU - Engstrøm, Thomas

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.

AB - Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.

KW - Aged

KW - Angina, Stable/surgery

KW - Angina, Unstable/surgery

KW - Cause of Death

KW - Denmark

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Myocardial Infarction/mortality

KW - Myocardial Ischemia/mortality

KW - Patient Readmission

KW - Patient Selection

KW - Percutaneous Coronary Intervention

KW - Randomized Controlled Trials as Topic

KW - ST Elevation Myocardial Infarction/mortality

U2 - 10.1016/j.ahj.2018.05.018

DO - 10.1016/j.ahj.2018.05.018

M3 - Journal article

VL - 204

SP - 128

EP - 138

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

ER -