We read with great interest the paper by Uppal et al1 on South Asian representation in cardiovascular trials. The authors highlight a significant gap—only ∼3% of more than 1 million trial participants were of South Asian ancestry.1 As practicing clinicians, we commend them for bringing attention to this under-representation, which has serious implications for evidence-based care in a high-risk population.
A key limitation underscored by Uppal and colleagues is that South Asian samples in many major trials are too small, making subgroup analyses statistically underpowered. For example, REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl [IPE]-Intervention Trial) included only 262 South Asian participants (∼3% of 8,179), resulting in an HR of ∼0.49 for the primary outcome in that subgroup with a 95% CI spanning 1.1 This wide interval reflects insufficient power and undermines confidence in the therapy’s effectiveness for South Asian patients. As a result, clinicians lack robust data to tailor guidelines for this population, even when a trend suggests benefit.
Another limitation is that trials rarely stratified results by risk factors prevalent in South Asians, such as elevated lipoprotein(a) or early-onset diabetes. South Asians have high rates of metabolic risk factors (eg, diabetes/prediabetes and hypertension) and often higher Lp(a) levels.2 Not accounting for these factors may dilute observed intervention effects and mask differences in treatment response, hindering personalized care.
Addressing these gaps requires proactive trial design changes. First, future trials should set prespecified enrollment targets to ensure sufficient South Asian participants for powered subgroup analysis. Second, trials can enrich enrollment of high-risk phenotypes common in South Asians (eg, elevated Lp(a), impaired fasting glucose) to better capture this population’s risk spectrum. Finally, adaptive designs can adjust recruitment in real time to boost inclusion of underrepresented groups as needed. These approaches would enhance subgroup power and improve the generalizability of trial findings.
We again commend the study from Uppal et al1 for exposing this representation gap in cardiovascular research. Their work is a crucial step toward more equitable evidence generation.1 By overcoming current barriers to inclusion, future cardiovascular trials can yield data that are more generalizable to South Asian patients, ensuring advances in therapy benefit all high-risk populations.
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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