Blinding and quality of life endpoints in randomised trials of stable angina: a meta-epidemiological study.

BACKGROUND

Quality of life (QoL) measures are commonly used in randomised trials assessing therapies for stable angina. As these outcomes rely on patient reporting, they are susceptible to placebo and expectation effects when blinding is absent. It remains unclear whether trials investigating QoL outcomes in stable angina routinely incorporate blinded designs.

METHODS

We performed a meta-epidemiological analysis of randomised controlled trials evaluating therapeutic interventions for stable angina, examining the association between QoL endpoint use and trial blinding. Trials were identified through systematic searches of MEDLINE from inception to February 2026. Trial characteristics including intervention type, QoL endpoint use and blinding status were extracted. QoL endpoint use was defined according to the primary endpoint where specified or any reported endpoint otherwise. Associations between QoL endpoint use and trial blinding were evaluated using Poisson regression to estimate adjusted prevalence ratios.

RESULTS

A total of 381 randomised trials were included, of which 58 (15%) incorporated QoL endpoints. QoL endpoint use increased over time. Blinding status was available for 355 trials; 308 (87%) trials reported participant blinding. Trials using QoL endpoints were less frequently blinded than those without QoL endpoints (54% vs 92%). In adjusted analyses, QoL endpoint use was associated with a lower likelihood of blinding (adjusted prevalence ratio 0.70, 95% CI 0.57 to 0.87, p=0.001). Findings remained consistent in a sensitivity analysis restricted to trials with explicitly stated primary endpoints. This pattern was observed across pharmacological, interventional and other therapies.

CONCLUSION

In randomised trials of therapies for stable angina, QoL endpoints are increasingly used but are less frequently accompanied by blinded trial designs. Given the vulnerability of subjective outcomes to bias, these findings highlight a potential blinding paradox in angina trials, whereby outcomes most prone to bias are often evaluated in studies that are less likely to incorporate blinding.

PROSPERO REGISTRATION NUMBER: CRD420261336319.