Study Metrics
Quality Indicators
Study Information
| First Author: | Baptiste |
| Publication Year: | 2024 |
| DOI: | https://doi.org/10.1093/aje/kwae137 |
| Preprint: | https://doi.org/10.1101/2022.12.02.22282220 |
Institution & Funding
| Institutions: | London School of Hygiene & Tropical Medicine, Queen Mary University of London, Friedrich Alexander University, McMaster University, Analysis Group Inc. |
| Funding: | Declared: Private, research institute, NGO |
| Funding Institutions: | This work was supported by the funding from a GlaxoSmithKline PhD studentship held by PB as part of an ongoing collaboration between GSK and the London School of Hygiene and Tropical Medicine. This research was funded in whole, or in part, by the Wellcome Trust [Senior Research Fellowship 224485/Z/21/Z to EW]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. |
Study Context
| Disease: | Cardiovascular disease |
| Disease Category: | Cardiology |
| Data Type: | Electronic Health Records |
| Number of Data Sources: | 3 |
| Geography: | UK |
| Eligible Sample: | 137155.0 |
| Number of Emulations: | 1 |
| Number of Treatments: | 2 |
Analytical Methods
| Missing Data Method: | Multiple imputation |
| Matching Method: | PS matching |
| Analysis Method: | Cox PH |
Quality Methods
Target Trial Information
| Target Trial Name: | ONTARGET |
| Registration Number: | NCT00153101 |
| Target Trial DOI: | https://doi.org/10.1056/NEJMoa0801317 |
TTE vs RCT Comparisons
Detailed comparison between Target Trial Emulation results and corresponding Randomized Controlled Trial outcomes.
≥30% increase in serum creatinine
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
≥30% increase in serum creatinine
RCT Result
1.14
95% CI: [0.80, 1.62]
vs
TTE Result
1.38
95% CI: [1.34, 1.43]
Concordance Assessment
CIs overlap, suggesting concordance
Both point to similar conclusion
Angioedema
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Angioedema
RCT Result
0.40
95% CI: [0.19, 0.86]
vs
TTE Result
1.14
95% CI: [0.72, 1.80]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Cough
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Cough
RCT Result
0.26
95% CI: [0.21, 0.33]
vs
TTE Result
1.29
95% CI: [1.16, 1.43]
Concordance Assessment
CIs do not overlap
Different conclusions
Death from any cause
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Death from any cause
RCT Result
0.98
95% CI: [0.90, 1.07]
vs
TTE Result
0.97
95% CI: [0.93, 1.01]
Concordance Assessment
CIs overlap, suggesting concordance
Both point to similar conclusion
Death from cardiovascular causes
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Death from cardiovascular causes
RCT Result
1.00
95% CI: [0.89, 1.12]
vs
TTE Result
0.96
95% CI: [0.90, 1.03]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Death from non-cardiovascular causes
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Death from non-cardiovascular causes
RCT Result
0.96
95% CI: [0.83, 1.10]
vs
TTE Result
0.97
95% CI: [0.92, 1.02]
Concordance Assessment
CIs overlap, suggesting concordance
Both point to similar conclusion
Hospitalisation for heart failure
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Hospitalisation for heart failure
RCT Result
1.12
95% CI: [0.97, 1.29]
vs
TTE Result
0.97
95% CI: [0.90, 1.05]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Main secondary outcome: Death from cardiovascular causes, myocardial infarction or stroke
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Main secondary outcome: Death from cardiovascular causes, myocardial infarction or stroke
RCT Result
0.99
95% CI: [0.91, 1.07]
vs
TTE Result
0.98
95% CI: [0.94, 1.02]
Concordance Assessment
CIs overlap, suggesting concordance
Both point to similar conclusion
Myocardial infarction
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Myocardial infarction
RCT Result
1.07
95% CI: [0.94, 1.22]
vs
TTE Result
0.97
95% CI: [0.92, 1.01]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Primary composite: Death from cardiovascular causes, myocardial infarction, stroke, or hospitalisation for heart failure
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Primary composite: Death from cardiovascular causes, myocardial infarction, stroke, or hospitalisation for heart failure
RCT Result
1.01
95% CI: [0.94, 1.09]
vs
TTE Result
0.98
95% CI: [0.94, 1.02]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Stroke
ONTARGETPopulation
High-risk patients aged ≥55 years with history of either coronary artery, peripheral artery, or cerebrovascular disease, or high-risk diabetes with end organ damage
Intervention
Angiotensin receptor blocker (ARB)
Comparison
Angiotensin-converting enzyme inhibitor (ACEi)
Outcome
Stroke
RCT Result
0.91
95% CI: [0.79, 1.05]
vs
TTE Result
1.04
95% CI: [0.97, 1.12]
Concordance Assessment
CIs overlap, suggesting concordance
Different conclusions
Transparency Indicators
Overall Transparency Score:
Conflicts & Funding
| Conflicts of Interest: | Declared: Financial |
| COI Institutions: | GSK, Compass Pathways, Ontario Ministry of Health, Sanofi, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim, Baxter, Fresenius Medical Care, AstraZeneca, Vifor Fresenius Medical Care, Relypsa, Bayer HealthCare, Novo Nordisk, UpToDate Inc., Idorisia, Labchem, Parexel, Roche |
| Funding Source: | Declared: Private, research institute, NGO |
| Funding Institutions: | This work was supported by the funding from a GlaxoSmithKline PhD studentship held by PB as part of an ongoing collaboration between GSK and the London School of Hygiene and Tropical Medicine. This research was funded in whole, or in part, by the Wellcome Trust [Senior Research Fellowship 224485/Z/21/Z to EW]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. |