Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials

Alexander Jobs; Shamir R Mehta; Gilles Montalescot; Eric Vicaut; Arnoud W J Van't Hof; Erik A Badings; Franz-Josef Neumann; Adnan Kastrati; Alessandro Sciahbasi; Paul-Georges Reuter; Frédéric Lapostolle; Aleksandra Milosevic; Goran Stankovic; Dejan Milasinovic; Reinhard Vonthein; Steffen Desch; Holger Thiele

doi:10.1016/S0140-6736(17)31490-3

Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials

Alexander Jobs, Shamir R Mehta, Gilles Montalescot, Eric Vicaut, Arnoud W J Van't Hof, Erik A Badings, Franz-Josef Neumann, Adnan Kastrati, Alessandro Sciahbasi, Paul-Georges Reuter, Frédéric Lapostolle, Aleksandra Milosevic, Goran Stankovic, Dejan Milasinovic, Reinhard Vonthein, Steffen Desch, Holger Thiele

Abstract

BACKGROUND: A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality.

METHODS: We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).

FINDINGS: We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive.

INTERPRETATION: An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients.

FUNDING: None.

Original language	English
Journal	The Lancet
Volume	390
Issue number	10096
Pages (from-to)	737-746
Number of pages	10
ISSN	0140-6736
DOIs	https://doi.org/10.1016/S0140-6736(17)31490-3
Publication status	Published - 19.08.2017

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10.1016/S0140-6736(17)31490-3

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Jobs, A., Mehta, S. R., Montalescot, G., Vicaut, E., Van't Hof, A. W. J., Badings, E. A., Neumann, F.-J., Kastrati, A., Sciahbasi, A., Reuter, P.-G., Lapostolle, F., Milosevic, A., Stankovic, G., Milasinovic, D., Vonthein, R., Desch, S., & Thiele, H. (2017). Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials. The Lancet, 390(10096), 737-746. https://doi.org/10.1016/S0140-6736(17)31490-3

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title = "Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials",

abstract = "BACKGROUND: A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality.METHODS: We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).FINDINGS: We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive.INTERPRETATION: An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients.FUNDING: None.",

author = "Alexander Jobs and Mehta, {Shamir R} and Gilles Montalescot and Eric Vicaut and {Van't Hof}, {Arnoud W J} and Badings, {Erik A} and Franz-Josef Neumann and Adnan Kastrati and Alessandro Sciahbasi and Paul-Georges Reuter and Fr{\'e}d{\'e}ric Lapostolle and Aleksandra Milosevic and Goran Stankovic and Dejan Milasinovic and Reinhard Vonthein and Steffen Desch and Holger Thiele",

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month = aug,

day = "19",

doi = "10.1016/S0140-6736(17)31490-3",

language = "English",

volume = "390",

pages = "737--746",

journal = "The Lancet",

issn = "0140-6736",

number = "10096",

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Jobs, A, Mehta, SR, Montalescot, G, Vicaut, E, Van't Hof, AWJ, Badings, EA, Neumann, F-J, Kastrati, A, Sciahbasi, A, Reuter, P-G, Lapostolle, F, Milosevic, A, Stankovic, G, Milasinovic, D, Vonthein, R, Desch, S & Thiele, H 2017, 'Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials', The Lancet, vol. 390, no. 10096, pp. 737-746. https://doi.org/10.1016/S0140-6736(17)31490-3

TY - JOUR

T1 - Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome

T2 - a meta-analysis of randomised trials

AU - Jobs, Alexander

AU - Mehta, Shamir R

AU - Montalescot, Gilles

AU - Vicaut, Eric

AU - Van't Hof, Arnoud W J

AU - Badings, Erik A

AU - Neumann, Franz-Josef

AU - Kastrati, Adnan

AU - Sciahbasi, Alessandro

AU - Reuter, Paul-Georges

AU - Lapostolle, Frédéric

AU - Milosevic, Aleksandra

AU - Stankovic, Goran

AU - Milasinovic, Dejan

AU - Vonthein, Reinhard

AU - Desch, Steffen

AU - Thiele, Holger

PY - 2017/8/19

Y1 - 2017/8/19

N2 - BACKGROUND: A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality.METHODS: We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).FINDINGS: We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive.INTERPRETATION: An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients.FUNDING: None.

AB - BACKGROUND: A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality.METHODS: We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988).FINDINGS: We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive.INTERPRETATION: An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients.FUNDING: None.

U2 - 10.1016/S0140-6736(17)31490-3

DO - 10.1016/S0140-6736(17)31490-3

M3 - Scientific review articles

C2 - 28778541

SN - 0140-6736

VL - 390

SP - 737

EP - 746

JO - The Lancet

JF - The Lancet

IS - 10096

ER -

Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials

Abstract

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