This news release does a nice job of explaining the basic design of a study investigating whether a once-daily “triple pill” (that combines 3 different blood pressure-lowering medications) is more effective in lowering blood pressure than doctors’ usual approach.
But there’s plenty of room for improvement here including: presenting the findings in a more meaningful context for patients, including the substantial adverse outcomes noted by the researchers, and using much more toned down language for results that are neither novel or all that significant.
Notably, there is a significant financial conflict of interest involving the authors. This should have been made clear to readers.
The global importance of poorly controlled high blood pressure is well-stated by the authors in the introduction to their study published in JAMA (paraphrased):
High blood pressure is the leading cause of mortality and cardiovascular disease globally with most of the disease burden occurring in low- and middle-income countries. The availability and affordability of medications is a critical issue. About one-third of individuals with high blood pressure in these settings receive treatment. Only about half of patients treated in high-income countries and about 1-in-4 patients in low- and middle-income countries achieve blood pressure control.
A fixed low-dose combination therapy with inexpensive blood pressure-lowering drugs has the potential to address several barriers to improve blood pressure control worldwide.
Indeed, there’s significant need for a simple-to-take, effective, and affordable medication to address this issue. If successful, the benefits to patients, and the profits for developers, would be massive.
The cost of the three-in-one pill is not mentioned.
Two similar pills already on the market (Tribenzor and Exforge HCT). They’re also once-daily pills combining an angiotensin II receptor blocker + calcium channel blocker + thiazide diuretic. They both have a retail price of approximately $10 a pill, or $300 per month [Source: Drugs.com].
The target blood pressure (BP) for this study was below 140/90 (or below 130/80 in patients with diabetes or chronic kidney disease).
The news release states that: “70% (of subjects) reached blood pressure targets with the ‘Triple Pill’, compared to just over half receiving normal care.” (Normal or usual care is defined in the release as “their doctor’s choice of blood pressure lowering medication.”)
It should have been made more clear this was measured after 6 months in the study. And as a result, the effect on cardiovascular (CV) risk reduction of the combination is unknown.
One of the goals of the approach using reduced dosage is to reduce the likelihood of side effects, but the side effects reported in the study were not mentioned in the news release, and include:
Overall, 419 adverse events in 255 patients (about 38% for the triple pill and 35% for usual care)
Of note, both groups experienced similar rates of musculoskeletal pain (roughly 7%), but the triple pill group had much more dizziness and fainting (5.2% vs. 2.8%) as well.
It should have been mentioned that combination antihypertensive (blood pressure lowering) medications are well known to have dozens of “major” drug interactions, and can also cause swelling and metabolic disturbances.
We were glad to see that the basic study design was included: 700 patients randomized to either receive the triple pill or usual care, with an average patient age of 56 years old, and a mean baseline blood pressure of 154/90. This qualifies as “mild” hypertension.
But it should have been made clear that while reduced blood pressure is a goal it is a surrogate goal. The real target of blood pressure reduction is reduced cardiovascular (CV) event rates. As we learned from previous research (ALLHAT trial), drugs that reduce blood pressure equally are not all created equally with regard to CV risk reduction.
A finding that should have been included in the news release is that — after 6 months of treatment — the triple pill group achieved a mean BP = 125/76 vs. the usual care a mean BP = 134/81.
That’s clinically relevant for two reasons. First, it clearly shows the difference in systolic blood pressure achieved by the triple pill group compared to the usual care group is only 9 mm of mercury. Not very clinically significant at the individual level, and arguably a modest achievement at the population level.
Finally, it would have been useful to note, as the authors noted in the study, that since the research was conducted in Sri Lanka, with its unique health system and culture, the results may not be generalized to Western, industrialized countries.
There is no disease-mongering here and a target blood pressure of <140/90 would be considered appropriate by many medical societies. It provides some context in terms of goals to reduce high blood pressure globally.
Although this is mentioned …
The study was funded by the National Health and Medical Research Council of Australia
… what’s not mentioned is that the two lead authors quoted in the news release both receive a salary from George Health Enterprises (GHE is the product commercialization arm of The George Institute for Global Health). According to disclosures cited in the published study:
George Health Enterprises has received investment funds to develop fixed-dose combination products containing aspirin, statin, and blood pressure-lowering drugs and has submitted a patent for the treatment of hypertension
The news release calls the pill “innovative” and says it “could transform the way blood pressure is treated around the world” … but it fails to mention that combination blood pressure-lowering medications have been around for decades. And, as mentioned above, there are some once-daily “triple pills” already on the market.
It’s implied (but not made very clear for readers) that the pill is in trials and, therefore, not commercially available.
Despite the fact that other combination blood pressure-lowering medications are available (but not mentioned), the headline and first paragraph of this news release suggest novelty. That’s potentially misleading for readers.
An editorial accompanying the study put this research in context in terms of what has been learned previously:
The TRIUMPH investigators have demonstrated the effects of a promising intervention in a triple half-dose combination therapy, which logically extends findings from prior research to improve BP control among patients with mild to moderate hypertension. This study contributes to the existing literature demonstrating the essential role of fixed-dose combination therapy as a viable strategy for BP control on a global scale.
This framing is premature, not supported by the study, and therefore unjustified:
Could transform the way high blood pressure is treated around the world … expected the findings will change guidelines globally … a major advance.