Hypertension, Women's Cardiovascular Health, and the KARDINAL Trial

Despite decades of progress in cardiovascular medicine, hypertension remains stubbornly difficult to control at the population level, and women continue to be underrepresented in the research that shapes treatment. At the 2026 American College of Cardiology meeting, Pharmacy Times spoke with Stacey Rosen, MD, FAHA, volunteer president of the American Heart Association and executive director of the Katz Institute for Women's Health at Northwell, about a novel RNA-based approach to blood pressure control, the KARDINAL trial (NCT06864104), and what it will take to finally close the gender gap in cardiovascular research.

Pharmacy Times: Uncontrolled hypertension remains stubbornly prevalent despite existing therapies. What is it about this new mechanism that offers a genuinely different approach?

Stacey Rosen, MD, FAHA: Hypertension affects almost half the population, and it is one of the most treatable underlying causes of poor health outcomes. Yet we know what to do—we just don't always know how to do it effectively. There are individual-level barriers: patients struggling to take their medications, adherence and compliance challenges, and necessary lifestyle changes that aren't always accessible. And then there are systemic barriers—health system gaps and societal factors that make long-standing, intractable hypertension very difficult to manage. So the idea of a new type of medication—one that decreases angiotensinogen production and is administered via monthly injection—may meaningfully improve adherence and remove one of the key obstacles we face in managing hypertension across a population.

Pharmacy Times: Heart disease is the number 1 killer of women, yet for decades most of what we know about treatment has come from studies of men. How is that finally starting to change?

Rosen: Thank goodness it is changing. Historically, the entire medical community—research and clinical practice—was focused on the male model. We extrapolated, assuming men and women were essentially the same, perhaps just a little smaller. Over the last 25 years, the American Heart Association's Go Red for Women initiative has shifted that focus considerably. We are now looking more uniquely at the health needs of women—not just for conditions like hypertension, but across all forms of cardiovascular disease. We know that women and men are not the same. We need to study them better, advocate for sex-specific research, and always ask: “how is this different for women?”

Pharmacy Times: KARDINAL was a phase 2 study. What was it primarily powered to demonstrate?

Rosen: KARDINAL enrolled patients with poorly controlled hypertension, all of whom were on multiple medications. The primary end points were 2-fold: first, to determine whether angiotensinogen production was meaningfully reduced, and second, to assess whether office blood pressure was lowered over a relatively short timeframe.

Pharmacy Times: What were the headline efficacy findings, and how meaningful are the blood pressure reductions in terms of overall cardiovascular risk?

Rosen: On the first end point, the medication did significantly lower angiotensinogen production, which was an important proof of concept. On the blood pressure side, I would characterize the short-term results as less definitive. Both groups initially received a dose, but only one group continued with subsequent doses—and at the end of the study period, there was no significant difference in blood pressure lowering between the two groups. So while the mechanism is promising, the efficacy signal on blood pressure needs further evaluation.

Pharmacy Times: How did the tolerability profile look, particularly given that side effects are a major driver of non-adherence?

Rosen: There were some concerning findings in the tolerability profile. There was one death that deemed unrelated to the drug by the site investigator. We have to look carefully at this. The overall risk profile has potential, but it may not be ideal for broad use as a second- or third-line agent across large populations. At least, not yet. More data will be needed.

Pharmacy Times: Would success in this space have broader implications for how the field approaches sex-specific cardiovascular drug development?

Rosen: Always. Whenever we are evaluating a new medication, we must enroll enough women to allow for meaningful disaggregation of the data. With a novel agent like this, that is critically important. We know women metabolize medications differently, and the way blood pressure responds to certain agents can differ between men and women. This has to be built into the research design from the start—not considered as an afterthought.