TARGET EU: The risk of angiooedema and other safety events in heart failure patients treated with sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors

26/05/2026
26/05/2026
EU PAS number:
EUPAS1000001002
Study
Ongoing
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Study summary
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Study identification

EU PAS number

EUPAS1000001002

Study ID

1000001002

Official title and acronym

TARGET EU: The risk of angiooedema and other safety events in heart failure patients treated with sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors

DARWIN EU® study

No

Study countries

Netherlands
United Kingdom

Study description

This case study is part of the broader TARGET EU project (EUPAS1000000539), which aims to advance the regulatory use of real-world data through the application of target trial emulation and estimand methodologies.

Background: Sacubitril/valsartan (SV) was superior to enalapril, an Angiotensin Converting Enzyme Inhibitor (ACEI), in delaying the time to the composite outcome of Heart Failure (HF) hospitalization or cardiovascular death in patients with Heart Failure and reduced Ejection Fraction (HFrEF) in the PARADIGM-HF trial. Angioedema was a safety outcome of special interest with a relative risk of 1.9 (95% CI 0.8-4.5) for the SV arm vs the enalapril arm. Nevertheless, the PARADIGM-HF population may not be fully representative of the real-world HF population and angioedema is a rare event, both of which render necessary the assessment of the risk of angioedema with SV on a larger scale and in the general HF population.

Objectives: The primary objective is to estimate the effect of treatment with SV vs ACEi on time to first angioedema event in patients with HF.

Methods: We will perform a Prevalent New User active comparator cohort study using linked electronic healthcare records from the UK CPRD Aurum and the Netherlands PHARMO. Eligible patients are adults with HF, initiating SV or treated with ACEI from 01/01/2014 until 31/03/2023 and September 2024 for CPRD and PHARMO, respectively. In the primary analysis a while on treatment strategy is used for treatment - related intercurrent events and a while alive strategy for all-cause mortality. We match new SV users with ACEI users based on their treatment history before the index date and on time-conditional propensity score. In the primary analysis we use a Cox proportional hazards model with supplemental analyses using an accelerated model to estimate restricted mean survival time at 3 and 5 years. Sensitivity analyses will assess the impact of departures from key assumptions.

Study status

Ongoing
Research institutions and networks

Institutions

Teamit Institute
Spain
First published:
12/03/2024
Institution Other ENCePP partner

Networks

Contact details

Vasiliki Tassopoulou 0000-0001-9610-5357

Primary lead investigator
ORCID number:
0000-0001-9610-5357

Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Data analysis start date

Planned:

Date of final study report

Planned:
Sources of funding
EMA
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable