No difference in CV outcomes with two common diuretics among veterans with hypertension
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CHICAGO — Among older veterans with hypertension, there was no difference in the incidence of major adverse CV events after treatment with hydrochlorothiazide compared with chlorthalidone, according to new research.
In the Diuretic Comparison Project, “chlorthalidone did not reduce the incidence of major cardiovascular outcomes or noncancer death compared to hydrochlorothiazide at doses commonly used in clinical practice, specifically hydrochlorothiazide 25 mg or chlorthalidone 12.5 mg,” Areef Ishani, MD, MS, director of primary and specialty care at VA Minneapolis Health Care, director of specialty care in the VA Midwest Health Care Network, and vice chair and professor in the department of medicine at the University of Minnesota, Minneapolis, said during a presentation at the American Heart Association Scientific Sessions. “Subgroup analyses suggested a difference in the primary outcome by the presence or absence of prior stroke or MI.”
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The Diuretic Comparison Project was a point-of-care clinical trial conducted in a real-world setting.
“We undertook this study as the first large randomized controlled trial comparing chlorthalidone to hydrochlorothiazide,” Ishani said.
Researchers enrolled 13,523 U.S. veterans aged at least 65 years with a recent systolic BP of 120 mm Hg or higher already taking hydrochlorothiazide 25 mg or 50 mg (mean age, 72 years; 97% men; 77% white; 45% in rural areas). Ninety-five percent of veterans were on the low does of hydrochlorothiazide at baseline. For the intervention, veterans either continued hydrochlorothiazide or were switched to chlorthalidone 12.5 mg.
The researchers reported no difference in systolic BP or potassium between the hydrochlorothiazide and chlorthalidone groups over time.
Over a median follow-up of 2.4 years, the incidence of the primary outcome — time to first major adverse CV event, defined as stroke, MI, non-cancer death, hospitalization for acute HF or urgent revascularization or unstable angina — was 10.4% in the chlorthalidone group compared with 10% in the hydrochlorothiazide group (HR = 1.04; 95% CI, 0.94-1.16; P = .4). There was also no difference in any of the individual components of the primary outcome, the researchers reported.
In a prespecified subgroup analysis, chlorthalidone was associated with a 27% reduction in the primary outcome among patients with a history of MI or stroke (HR = 0.73; 95% CI, 0.57-0.94) compared with a 12% increase in patients without prior MI or stroke (HR = 1.12; 95% CI, 1-1.26; P for interaction = .035).
Ishani said there was a slight increase in risk for laboratory-identified hypokalemia in the chlorthalidone group compared with the hydrochlorothiazide group (6% vs. 4.4%; HR = 1.38; 95% CI, 1.19-1.6).
Reference:
- No difference in heart outcomes found in use of two diuretics to treat blood pressure. https://newsroom.heart.org/news/no-difference-in-heart-outcomes-found-in-use-of-two-diuretics-to-treat-blood-pressure. Published Nov. 5, 2022. Accessed Nov. 5, 2022.
Perspective
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Edward T.A. Fry, MD, FACC, FSCAI
With the exception of hypokalemia, it didn't look like that there was any kind of negative difference or adverse effects related to chlorthalidone. Then there was the question of the subgroup analysis of patients with prior MI or stroke in terms of whether there was some benefit. It probably means that there is not a lot of difference in change of practice. I don't know exactly what the percentage utilization of one vs. another is, but I would just say from my own experience, hydrochlorothiazide is used 90% of the time.
Chlorthalidone is often used as a switchover if you think people are not making progress on hydrochlorothiazide. One of the other take home messages from this study would then be, with the exception of being careful about hypokalemia, it's not an irrational strategy. If you're not reaching the goal with one, that you could perhaps try the other, with the exception of the hyperemia, without too much concern.
Because IRONMAN was conducted through the VA, is this applicable to women? It was also an older patient population. The average age was 72 and there were a lot of risk factors. Forty-five percent of them had diabetes. Especially in a primary prevention and to a lesser extent secondary prevention trial, was the cake already baked? Would there be a different scene in patients who are a younger population where maybe there's a greater impact of addressing the risk factors?
Another concept came up in the comments that Robert Califf, MD, MACC, gave earlier about this widening divide in health care outcomes between rural and urban populations. In the DCP trial, 45% of participants were from rural areas. That's important.
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Manesh R. Patel, MD, FACC, FAHA, FSCAI
DCP was conducted in the VA system and Dr. Ishani did an amazing job describing what they did across multiple VA systems to identify patient providers, consent them and then consent the patients verbally and randomly assigned them to BP control either continued hydrochlorothiazide or chlorthalidone. Then they used the electronic health record system to identify the events.
For CV events, there was no difference between chlorthalidone or hydrochlorothiazide, an important result for people who are taking care of patients where we are sometimes making decisions between these two commonly used agents.
There is no compelling reason, unless something else is going on differently or there are issues with tolerance, to change the agent if they’re already taking either hydrochlorothiazide or chlorthalidone. Most of the patients in the country are on hydrochlorothiazide, and I think that informs our practice today.
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Ishani A, et al. LBS.01: The Main Event: Changing Clinical Practice. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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