Authors’ reply: Systolic blood pressure targets below 120 mmHg are associated with reduced mortality: A meta-analysis

Dear Editor,

We thank Dr. Shamsulddin for his perspective [1] on our meta-analysis on intensive versus standard systolic blood pressure (SBP) control [2]. Although our findings show consistent benefits of intensive SBP control, we agree that identifying individuals who are most likely to benefit or experience harm remains a significant challenge.

Generalizability is a common limitation of trial-level meta-analyses, particularly when the included studies are geographically concentrated. In our analysis, most participants were enrolled in studies conducted in North America and East Asia. Although heterogeneity across study populations may compromise the precision and interpretability of pooled effect estimates, a certain degree of clinical and methodological variation is essential to support the external validity and applicability of meta-analytic findings. Besides geographical diversity, the included studies enrolled patients with different risk profiles, including diabetes, history of stroke, and cardiovascular disease of varying severity. Nonetheless, our subgroup analyses did not show significant heterogeneity of treatment effect across these clinical strata, suggesting a consistency that could be interpreted as a pragmatic proxy for real-world variability. However, this does not serve as a substitute for specifically designed regional studies, which would be required to confirm the benefits of intensive SBP control in genetically diverse populations and within different healthcare systems.

Finally, the risk of adverse events, such as the incidence of syncope, acute kidney injury and electrolyte disturbances, may also differ between geographical and clinical subgroups. These aspects of heterogeneity are rarely addressed in clinical trials and meta-analyses, which are often limited to subgroup analyses for efficacy outcomes.

Although we welcome the call for global validation, we believe our findings provide robust evidence supporting the benefits of intensive blood pressure lowering across diverse populations. Clinicians should use this evidence to guide personalized treatment decisions.

The authors declare no conflicts of interest.