Social Justice and the Polypill: A Strategy for the Future of Health Equity

The American Heart Association Scientific Sessions kicked off this morning in everything but the usual fashion—socially distant, virtual, absent the normal red regalia and buzzing convention center. And yet, it felt as though the necessary distance created space for a kind and level of discussion and introspection I’ve never before experienced during a large scientific conference. In particular, the Opening Session set the stage for the day with a thoughtful and deliberate discussion of racial and gender inequity featuring the inimitable Drs. Nanette Wenger and Eugene Braunwald along with moderators Drs. Clyde Yancy and Robert Harrington. The session covered historical aspects of the fight for equity in medicine told from the experienced perspectives of Drs. Wenger and Braunwald, while recognizing how far we’ve come—and have yet to go—in realizing the promise of an equitable society and equitable healthcare. That the session was quickly followed by one on how best to use behavioral interventions to advance equity, and then another forum on how training programs can adopt antiracist behaviors and policies, demonstrated the depth of the commitment to address equity and disparities during this year’s Scientific Sessions.

I was, however, most enamored by the first late-breaking clinical trial presentation of the day, summarizing the results of the International Polycap Study 3 (TIPS-3) clinical trial, simultaneously published today in the New England Journal of Medicine.1 In an introduction by Dr. Dorairaj Prabhakaran, it was immediately evident how TIPS-3, a clinical trial evaluating a polypill containing low-dose simvastatin, atenolol, hydrochlorothiazide, and ramipril, fit perfectly within the context of the broader discussions of equity and social justice that permeated the day. The polypill, after all, is less the new-tech that many of us have come to expect in late-breaking sessions, and more a study in improving access to care. Noting the enormous burden of cardiovascular disease (CVD) in low- and middle-income countries, and the marked inter-and intra-country disparities observed in cardiovascular outcomes, Dr. Prabhakaran set the stage for how the polypill was—when all is said and done—a strategy study with the goal of improving equity. He summarized this idea simply and eloquently, concluding that while “medicine is inherently reductionist… the solutions have to be holistic.”

The TIPS-3 study, subsequently presented by Drs. Salim Yusuf and Prem Pais, evaluated the effects of the polypill and primary prevention aspirin against placebo in a two-by-two factorial design within an intermediate-risk population without preexisting CVD. The trial recruited 5713 participants from more than nine countries including India, the Philippines, Colombia, Bangladesh, Canada, and Malaysia, among others. Participants were followed for more than 4.5 years for a primary outcome of major CVD (including cardiovascular death, non-fatal stroke, non-fatal myocardial infarction), heart failure, resuscitated cardiac arrest, or revascularization. Despite achieving lower-than-anticipated levels of blood pressure and LDL-cholesterol reduction (5.8 mmHg and 19 mg/dL, respectively in the polypill arm), the trial saw a 21% reduction in the primary outcome in the polypill arm when compared to placebo (HR 0.79; 95% confidence interval [CI], 0.63 to 1.00), and an even more impressive 31% reduction in the aspirin + polypill group (HR 0.69; CI, 0.50 to 0.97). Unsurprisingly, aspirin alone did not significantly reduce the incidence of cardiovascular events, though this finding does make the additive reduction in CV events in the polypill + aspirin arm more unusual. The benefit of treatment with polypill + aspirin was, moreover, seen early (within the first two years of the trial), and was evident despite relatively high rates of discontinuation of therapy in the follow-up, driven primarily by logistical challenges in obtaining therapies.

With these findings, TIPS-3 adds to the growing and consistent body of evidence from prior trials including HOPE-32 and PolyIran study3, demonstrating that polypills have the potential to impact both intermediate endpoints and cardiovascular outcomes in a primary prevention population. The potential of the strategy to impact cardiovascular disparities is apparent, but the true test of our commitment to health equity globally will be seen in whether we are able to translate such findings into meaningful programs and interventions in the coming years.



  1. Yusuf S, Joseph P, Dans A, et al. Polypill with or without Aspirin in Persons without Cardiovascular Disease. New England Journal of Medicine 2020.
  2. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2021-2031.
  3. Roshandel G, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet. 2019;394(10199):672-683.



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