Related Experiment Videos

Surrogacy of composite endpoints for mortality in trials of atherosclerotic cardiovascular disease

Ilan Richter1, Dafna Yahav2, Danielle R Rome3

  • 1Division of Cardiology, Columbia University Irving Medical Center, NY, New York, USA.

International Journal of Cardiology
|May 26, 2026
PubMed

Insights

Composite endpoints in cardiovascular trials do not reliably predict patient outcomes like mortality. Researchers found poor correlation between composite outcomes and actual patient prognosis, urging a shift towards more patient-centered trial designs.

Area of Science:

  • Cardiology
  • Clinical Trials
  • Biostatistics

Background:

  • The reliability of composite endpoints in predicting patient mortality in cardiovascular trials is not well-established.
  • Modern composite endpoints are frequently used in randomized controlled trials (RCTs) for atherosclerotic cardiovascular disease (ASCVD).

Purpose of the Study:

  • To assess the surrogacy of composite endpoints used in recent ASCVD RCTs for cardiovascular and all-cause mortality.
  • To determine if components of composite endpoints correlate with patient prognosis.

Main Methods:

  • A systematic review of primary publications of RCTs for non-acute ASCVD using composite endpoints (≥3 components) published in top-tier journals from 2019-2023.
  • Trial-level surrogacy was evaluated using the R² coefficient of determination, with R² ≥ 0.8 set as the threshold for validation.

Main Results:

  • Forty-five RCTs met the inclusion criteria; 42% focused on secondary prevention.
  • None of the composite endpoint components met the R² ≥ 0.8 threshold for surrogacy of all-cause mortality.
  • The correlation coefficient for cardiovascular death was 0.54, with lower correlations observed for other outcomes like myocardial infarction and stroke.

Conclusions:

  • Components of composite endpoints in large ASCVD RCTs published in high-impact journals show a lack of correlation with patient prognosis.
  • There is a need for journal editors, regulators, and healthcare professionals to advocate for clinical trial evidence that better reflects patient outcomes.
  • Improved alignment of trial evidence with patient outcomes is crucial for informed decision-making in cardiovascular care.
Abstract

Keywords:
ASCVDCompositeDeath surrogateOutcomesRCT

Related Concept Videos

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
Kaplan-Meier Approach01:24

Kaplan-Meier Approach

The Kaplan-Meier estimator is a non-parametric method used to estimate the survival function from time-to-event data. In medical research, it is frequently employed to measure the proportion of patients surviving for a certain period after treatment. This estimator is fundamental in analyzing time-to-event data, making it indispensable in clinical trials, epidemiological studies, and reliability engineering. By estimating survival probabilities, researchers can evaluate treatment effectiveness,...
Study Designs in Epidemiology01:20

Study Designs in Epidemiology

Epidemiological study designs are fundamental tools for investigating the distribution, determinants, and control of health conditions in populations. They help researchers understand the relationships between exposures and outcomes, and they broadly fall into two categories: "observational" and "experimental" studies.
Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and case-control studies.
Acute Coronary Syndrome III: Diagnostic Studies01:30

Acute Coronary Syndrome III: Diagnostic Studies

Diagnosing acute coronary syndrome or ACS begins with a thorough patient history. Notable symptoms include central, crushing chest pain radiating to the left arm, neck, jaw, or back, along with shortness of breath, sweating (diaphoresis), nausea, vomiting, dizziness, and palpitations.It is crucial to note any history of cardiac illnesses and assess risk factors, including age, gender, smoking, hypertension, diabetes, hyperlipidemia, and a sedentary lifestyle.During physical examination, vital...