Enhancing South Asian Representation in Cardiovascular Trials

Corresponding Author

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide.¹ South Asian individuals, originating from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka, experience disproportionately elevated CVD risk.^2,3 Despite constituting approximately one-quarter of the global population, South Asians exhibit higher rates of CVD in their countries of origin and in diaspora communities.^4,5 This elevated burden reflects the interplay of environmental factors, sociocultural influences,⁶ and distinctive predispositions, such as preferential visceral adiposity and elevated proinflammatory protein concentrations.7, 8, 9 However, South Asians continue to be markedly underrepresented in cardiovascular randomized controlled trials (RCTs).^10,11

In this issue of JACC: Asia, Uppal et al¹² examined 310 cardiovascular randomized controlled trials published between 2018 and 2022, encompassing 1,036,737 participants. Of these, only 3.2% were South Asian, and 75% of that subgroup came from trials conducted within South Asia. Excluding the single large ACS Quik trial, whose participants were exclusively Indian, reduces South Asian representation to just 1.1% of the total cohort. Only 35 of the 310 trials enrolled South Asians, and among the 80 trials reporting postrandomization race or ethnicity data, South Asians comprised 7.3%, dropping to 1.8% without the ACS Quik trial. Moreover, the review highlighted how South Asians were entirely absent from trials addressing heart failure, cardiac arrest, and valvular heart disease, and only 7.3% of participants with postrandomization outcome data were of South Asian origin.¹²

While the review did not identify studies on specific conditions, such as heart failure and cardiac arrest, a few notable examples of RCTs, such as EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6¹³ for heart failure and SAHARA (South Asian Heart Risk Assessment)¹⁴ intervention for myocardial infarction risk were noted. However, these studies fell outside the review's search criteria and may not have been accounted for in the analysis. The review by Uppal et al offers valuable insights and there are several methodological considerations that could enhance the comprehensiveness and robustness of future studies. The rationale for selecting the study years (2018-2022) was not clearly articulated, and the search was limited to journals such as The New England Journal of Medicine, The Journal of the American Medical Association, and The Lancet. While these journals are reputable, this narrow approach may have missed valuable studies published elsewhere. Future reviews could benefit from adopting a more expansive search strategy that encompasses a wider array of journals, databases, and clinical trial registries. This broader approach will help capture a more diverse set of studies, enriching the analysis. While the review did not explicitly mention the use of systematic review software like Covidence or the involvement of a medical librarian, incorporating these resources could further enhance the search process. Utilizing such tools and expertise can help ensure a comprehensive exploration of the literature, ultimately contributing to a more inclusive understanding of cardiovascular trials involving South Asian populations.

To enhance the inclusion of South Asian populations in cardiovascular trials, several strategic initiatives can be considered (Table 1). First, formative research should be undertaken to elucidate participation barriers, including length of residence, migration trajectory, socioeconomic status, and language proficiency. This will disentangle effects of acculturation, social disadvantage, and communication barriers on both CVD risk and treatment response. Second, RCTs must integrate South Asian stakeholders into governance by appointing community members to a community advisory board. These advisors should participate actively in the study’s conceptualization, design, site selection, recruitment strategies, and dissemination plans, ensuring that research questions and endpoints reflect community priorities. Meaningful partnership with community advisors will enhance trial relevance, optimize recruitment and retention, and increase the likelihood that findings will translate into actionable, sustainable improvements in cardiovascular health. A strong example of formative research and community engagement pre-RCT is SAHELI (South Asian Healthy Lifestyle Intervention), a 16-week, culturally adapted, group-based lifestyle intervention in South Asians with CVD risk factors.¹⁵ Third, trial sites should be expanded to include diaspora communities through partnerships with local health centers and cultural organizations. Embedding trials within trusted community institutions and employing culturally concordant staff may overcome barriers related to transportation, time constraints, and mistrust. Fourth, study designs must be sufficiently powered to permit South Asian–specific analyses. This includes oversampling within multiethnic trials or conducting dedicated RCTs focused on South Asian populations. This will prevent underpowered subgroup analyses that render results inconclusive. Fifth, investigators must adopt nuanced analytical frameworks that distinguish genetic ancestry from the sociopolitical constructs of race or ethnicity.¹⁶ South Asian representation in clinical research is critical to account for social considerations, including the intersectionality of socioeconomic, environmental, and cultural determinants. Recognizing that genetic variation at the population level is rooted in ancestral inheritance rather than socially assigned categories will allow researchers to identify true sources of clinical differences.¹⁶ Last, dissemination of trial results must prioritize accessibility and relevance to South Asian communities. Beyond traditional academic publications, study findings should be returned directly to participants through informational materials produced in English and relevant spoken languages, with translations led by community members. Town hall meetings in community venues will facilitate interactive dialogue, reinforce trust, and empower individuals to translate research insights into meaningful changes in prevention and care.

Table 1.

Context-Specific Strategies to Increase South Asian Participation in Cardiovascular RCTs

Strategy	Details	South Asia Countries	Host Countries
Formative research	Undertake research to elucidate participation barriers, including length of residence, migration trajectory, socioeconomic status, and language proficiency.	Conduct local studies to identify barriers specific to the region, such as limited health care access and cultural beliefs.	Conduct studies to identify barriers specific to diaspora communities, such as language barriers and cultural adaptation challenges.
Community engagement	Integrate South Asian stakeholders into governance by appointing community members to a community advisory board. These advisors should participate actively in protocol development, site selection, recruitment strategies, and dissemination plans.	Establish local community advisory boards to ensure cultural relevance and trust.	Establish diaspora community advisory boards to address unique challenges faced by immigrant populations.
Site expansion	Expand trial sites to include diaspora communities through partnerships with local health centers and cultural organizations. Embed trials within trusted community institutions and employ culturally concordant staff.	Partner with local health centers and cultural organizations to build trust and accessibility.	Partner with local health centers and cultural organizations serving diaspora communities to overcome transportation and time constraints.
Study design and power	Ensure that study designs are sufficiently powered to permit South Asian–specific analyses. This includes oversampling within multiethnic trials or conducting dedicated RCTs focused on South Asian populations.	Design studies with sufficient power for local South Asian–specific analyses, considering regional genetic and environmental factors.	Design studies with sufficient power for diaspora South Asian–specific analyses, considering the unique health profiles of immigrant populations.
Analytical frameworks	Adopt nuanced analytical frameworks that distinguish genetic ancestry from the sociopolitical constructs of race or ethnicity.	Use frameworks that account for local genetic and sociopolitical factors, such as regional dietary patterns and environmental exposures.	Use frameworks that account for diaspora genetic and sociopolitical factors, such as acculturation and socioeconomic disparities.
Dissemination of results	Prioritize accessibility and relevance to South Asian communities. Return study findings directly to participants through informational materials produced in English and relevant spoken languages, with translations led by community members. Organize town hall meetings in community venues.	Disseminate results in local languages and through local community venues to ensure wide reach and understanding.	Disseminate results in relevant spoken languages and through diaspora community venues to address language barriers and cultural differences.

RCT = randomized controlled trial.

Redressing the underrepresentation of South Asians in cardiovascular RCTs is both an ethical imperative and a scientific necessity. Inclusive research practices will refine clinical guidelines, optimize therapeutic strategies, and mitigate the disproportionate burden of CVD among South Asian populations. Although the review by Uppal et al did not address sudden cardiac death, a major cause of mortality in South Asians globally, it should nonetheless serve as both a wake-up call and a roadmap, guiding the cardiovascular research community toward a more inclusive, culturally informed, and ultimately more effective evidence base for all populations. Collectively, strategies to increase South Asians participation in RCTs should consider community engagement, cultural sensitivity, trust and representation, access, awareness of benefits through education, and establishment of international networks of collaboration within the context the countries of origin and host countries.

Funding Support and Author Disclosures

Dr Ramos was supported by National Institute on Minority Health and Health Disparities grant R01MD019956 and the Gordon and Betty Moore Foundation via the University of California Davis Betty Irene Moore Fellowship for Nurse Leaders and Innovators (principal investigator: S.R.R.; grant GBMF9048). Dr Boutjdir was supported by National Heart, Lung and Blood Institute grants R25HL105446 and R01HL164415. Dr Pondugula has reported that she has no relationships relevant to the contents of this paper to disclose.