By Wayne Batchelor, Paul Underwood, Roxana Mehran, Vishal Dahya and Lisa Currier
The PLATINUM DIVERSITY trial was initiated last year with the aim of evaluating the clinical outcomes of an everolimus-eluting stent (Promus Premier, Boston Scientific) in patient populations that have been traditionally under-served by clinical trials (eg. women and minorities). Study investigators, Wayne Batchelor, Paul Underwood, Roxana Mehran and others explain why data for these patients are urgently needed.
Data from cardiovascular clinical trials serve as the basis for clinicians to make important daily treatment decisions. Despite an increasingly diverse US population,1 clinical trials evaluating new medical and device therapies for cardiovascular disease have historically enrolled a disproportionately low number of women and minorities.2 It is estimated that approximately 35% of participants in recent cardiovascular research trials have been women.2 However, only 31% of these studies report outcomes by gender.2 Similarly, while African Americans make up 12% of the US population, they comprise only 3–5% of the patients enrolled in clinical trials.2,3 Hispanics, who now represent nearly 16% of the US population, account for a mere 1% of study patients.3 As a result, our understanding of the safety and efficacy of a range of cardiovascular therapies, including coronary stent procedures, in women and minorities remains incomplete. Considering that current US demographic trends predict that minorities will constitute the majority of the US population between 2040 and 2050,1 these disparities will become increasingly relevant in the future.
Not surprisingly, there is very little clinical and angiographic outcomes data for minorities and women undergoing coronary stent procedures. However, a number of noteworthy observations have surfaced, at least with regards to the impact of gender and race on stent selection and overall clinical outcomes.4,5 In 2007, Hannan et al showed that African Americans and patients with lower socioeconomic status tended to receive drug-eluting stents less frequently and bare metal stents more often than their Caucasian counterparts.4 A study by Rao et al showed that race, gender and age all significantly influenced the likelihood of a patient receiving a drug-eluting stent versus a bare metal stent.5 Several retrospective studies have shown higher rates of early and/or late drug-eluting stent thrombosis and myocardial infarction in African American patients undergoing percutaneous coronary intervention (PCI) than that noted in non-blacks, even after accounting for imbalances in baseline characteristics.6,7,8 We, and others, have recently shown that this incremental risk of late myocardial infarction could be as much as 3–5 fold higher for blacks.6,8 A recent large study of more than 400,000 patients, of whom more than 390,000 were white, also reported higher adverse events after PCI for black and Hispanic patients compared with Caucasians.9 Despite these concerning findings, several studies have shown that drug-eluting stents still provide more favourable outcomes in African American patients than do bare metal stents.7,9
It is important to note the limitations of these prior studies. The larger studies have been retrospective administrative databases, which have generally lacked detailed socioeconomic, clinical and angiographic data.6,7,9 Other studies, which have reported more detailed clinical and angiographic data, have tended to be small and underpowered or have lacked long-term follow-up. Therefore, we have yet to define if and how race and/or gender might be associated with incremental risk in contemporary PCI, particularly in the era of newer generation drug-eluting stents. For example, is race, gender or ethnicity associated with altered biological responses to drug-eluting stents or adjunctive medications, or is the incremental risk conferred by other factors, such as differences in baseline clinical characteristics, socioeconomic status, medication compliance, coronary disease severity or lesion characteristics? These and many other questions warrant further exploration.
The disparities mentioned above form the basis for the PLATINUM DIVERSITY trial. This study aims to help fill the outcomes data gap for women and minorities undergoing contemporary PCI. This prospective, multicentre study will evaluate the one-year clinical outcomes of an everolimus-eluting stent (Promus Premier, Boston Scientific) in 1,500 women, blacks and Hispanics enrolled in up to 65 sites across the US socioeconomic status, level of education, health insurance status, primary language, language concordance/discordance between patient and physician, and patient access to healthcare will be recorded at baseline. Detailed angiographic and procedural characteristics will be collected and medications will be logged (including adherence to dual anti-platelet therapy) and tracked over time. Patients will be followed at 30 days, 180 days and one-year post-procedure, and the primary endpoint of the study will be a composite of death, myocardial infarction and target vessel revascularisation. Several secondary endpoints will also be evaluated, including all-cause death, cardiac death, definite/probable stent thrombosis (using the Academic Research Consortium, or ARC definition), myocardial infarction rates and target vessel/lesion failure rates. Symptom status at baseline and follow-up will be assessed using the Canadian Cardiovascular Society (CCS) angina scale.
Enrolment in one subgroup (women, black and Hispanic) may be stopped to ensure sufficient enrolment in the other groups. The primary outcome will be compared across each of these groups and the one-year data from Caucasian male controls enrolled in the Promus Element Plus Post Approval Study.10 The PLATINUM DIVERSITY study will provide approximately 80% statistical power to detect a 3% difference in the primary endpoint between (1) the Caucasian male controls and women, and (2) the Caucasian male controls and the minority groups. Enrolment has already started and is anticipated to be completed by June 2016.
In summary, despite efforts to include gender and racially diverse subjects in clinical trials, current approaches are not successful at achieving this goal. The prospective and selective enrolment of women and minorities in the PLATINUM DIVERSITY study is unprecedented and will efficiently provide much needed contemporary coronary drug-eluting stent outcomes data for these under-represented groups. The goals of this study are aligned with recent efforts from the National Institutes of Health11 and the FDA12 to mandate more diversity in clinical studies. By broadening the demographic spectrum of contemporary PCI outcomes, we hope that this study will add substantially to the existing PCI database in a meaningful way.
- US census. http://www.census.gov/population/projections/files/analytical-document09.pdf.
- American Heart Association. http://blog.heart.org/fda-hearing-highlights-research-gaps-for-women-minorities-and-the-elderly/.
- Coakley et al. Journal of Women’s Health 2012;21: 713–16
- Hannan et al. The American Journal of Cardiology 2007; 100: 1192–98.
- Rao et al. American Heart Journal 2006; 152: 321–26.
- Collins et al. Circulation 2010; 122: 1085–90.
- Poludasu et al. Coronary Artery Disease 2008; 19: 551–57.
- Batchelor et al. Journal of interventional cardiology 2013; 26: 49–57.
- Kumaret al. Circulation 2013; 127: 1395–1403.
Wayne Batchelor, Southern Medical Group, assistant professor of Medicine, Florida State College of Medicine; president, Tallahassee Research Institute, Tallahassee, USA
Paul Underwood, medical director, Interventional Cardiology, Boston Scientific
Roxana Mehran, professor of Medicine, Cardiology, Mount Sinai Hospital, New York, USA
Vishal Dahya, resident physician, Florida State University College of Medicine, Tallahassee, USA
Lisa Currier, clinical trial manager, Clinical Interventional Cardiology, Boston Scientific (USA)