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Review
. 2022;147(3):235-247.
doi: 10.1159/000524948. Epub 2022 May 10.

Unstable Angina as a Component of Primary Composite Endpoints in Clinical Cardiovascular Trials: Pros and Cons

Anna Meta Dyrvig Kristensen  1 , Manan Pareek  2 , Kristian Hay Kragholm  3 , Thomas Steen Gyldenstierne Sehested  1   4 , Michael Hecht Olsen  5   6 , Eva Bossano Prescott  1
Affiliations
Review

Unstable Angina as a Component of Primary Composite Endpoints in Clinical Cardiovascular Trials: Pros and Cons

Anna Meta Dyrvig Kristensen et al. Cardiology. 2022.

Abstract

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.

Keywords: Acute coronary syndromes; Angina; Clinical trials; Composite endpoint; Unstable angina.

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Conflict of interest statement

Dr. Manan Pareek declares the following disclosures (all unrelated to the content of the present manuscript): Advisory Board − AstraZeneca, Janssen-Cilag; Speaker's Fee − AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag. The other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Pros and cons of using UA as an endpoint in cardiovascular clinical trials.
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