TY - JOUR

T1 - Unstable Angina as a Component of Primary Composite Endpoints in Clinical Cardiovascular Trials

T2 - Pros and Cons

AU - Kristensen, Anna Meta Dyrvig

AU - Pareek, Manan

AU - Kragholm, Kristian Hay

AU - Sehested, Thomas Steen Gyldenstierne

AU - Olsen, Michael Hecht

AU - Prescott, Eva Bossano

N1 - Publisher Copyright: © 2022 The Author(s). Published by S. Karger AG, Basel.

PY - 2022

Y1 - 2022

N2 - Background: Unstable angina (UA) is a component of acute coronary syndrome that is only occasionally included in primary composite endpoints in clinical cardiovascular trials. The aim of this paper is to elucidate the potential benefits and disadvantages of including UA in such contexts. Summary: UA comprises <10% of patients with acute coronary syndromes in contemporary settings. Based on the pathophysiological similarities, it is ideal as a part of a composite endpoint along with myocardial infarction (MI). By adding UA as a component of a primary composite endpoint, the number of events and feasibility of the trial should increase, thus decreasing its size and cost. Furthermore, UA has both economic and quality of life implications on a societal and an individual level. However, there are important challenges associated with the use of UA as an endpoint. With the introduction of high-sensitivity troponins, the number of individuals diagnosed with UA has decreased to rather low levels, with a reciprocal increase in the number of MI. In addition, UA is particularly challenging to define given the subjective assessment of the index symptoms, rendering a high risk of bias. To minimize bias, strict criteria are warranted, and events should be adjudicated by a blinded endpoint adjudication committee. Key Messages: UA should only be chosen as a component of a primary composite endpoint in cardiovascular trials after thoroughly evaluating the pros and cons. If it is chosen to include UA, appropriate precautions should be taken to minimize possible bias.

AB - Background: Unstable angina (UA) is a component of acute coronary syndrome that is only occasionally included in primary composite endpoints in clinical cardiovascular trials. The aim of this paper is to elucidate the potential benefits and disadvantages of including UA in such contexts. Summary: UA comprises <10% of patients with acute coronary syndromes in contemporary settings. Based on the pathophysiological similarities, it is ideal as a part of a composite endpoint along with myocardial infarction (MI). By adding UA as a component of a primary composite endpoint, the number of events and feasibility of the trial should increase, thus decreasing its size and cost. Furthermore, UA has both economic and quality of life implications on a societal and an individual level. However, there are important challenges associated with the use of UA as an endpoint. With the introduction of high-sensitivity troponins, the number of individuals diagnosed with UA has decreased to rather low levels, with a reciprocal increase in the number of MI. In addition, UA is particularly challenging to define given the subjective assessment of the index symptoms, rendering a high risk of bias. To minimize bias, strict criteria are warranted, and events should be adjudicated by a blinded endpoint adjudication committee. Key Messages: UA should only be chosen as a component of a primary composite endpoint in cardiovascular trials after thoroughly evaluating the pros and cons. If it is chosen to include UA, appropriate precautions should be taken to minimize possible bias.

KW - Acute coronary syndromes

KW - Angina

KW - Clinical trials

KW - Composite endpoint

KW - Unstable angina

U2 - 10.1159/000524948

DO - 10.1159/000524948

M3 - Review

C2 - 35537418

AN - SCOPUS:85134083435

VL - 147

SP - 235

EP - 247

JO - Cardiologia

JF - Cardiologia

SN - 0008-6312

IS - 3

ER -