ultra-low-dose 4-in-1 blood pressure pill

Study shows ultra-low-dose 4-in-1 blood pressure pill would be cost-effective in Australia

Treating high blood pressure with a ‘quadpill’ tablet containing very low doses of four commonly used, low-cost medicines is not only more effective than usual care but is also comparably cost-effective, according to a new analysis by researchers at The George Institute for Global Health.1

Published today in the journal Heart, the research involved economic modelling using clinical outcomes from the previous QUARTET2 trial of efficacy and safety, and current costs of medicines and healthcare appointments in Australia.

Lead author Dr Emily Atkins, Senior Research Fellow at The George Institute for Global Health, said the findings were significant, because treatment for high blood pressure (hypertension) in Australia has stagnated, creating opportunity for improvement to reduce preventable deaths and disease.

“The traditional treatment approach, recommended in the Australian guidelines for hypertension, is initially to use a single agent for most people, only moving onto combination treatment if they fail to achieve targeted reductions,” she said. “But this rarely achieves sustained control.”

“While the QUARTET trial found the ultra-low-dose combination treatment strategy significantly improved blood pressure control, our analysis projects that a quadpill would also be cost effective over a lifetime, compared to initial monotherapy, in the Australian setting,” Dr Atkins said. 

It is estimated that one in three adult Australians has high blood pressure, increasing their risk for many chronic conditions including heart disease, stroke and chronic kidney disease. The Australian Institute of Health and Welfare reported that only a third of blood pressure cases were under control in 2017-2018, implying that over two thirds of people with raised blood pressure in Australia were not properly managed. This situation has not improved for the past ten years.

The new study calculated the cost of care for 591 adults with high blood pressure, who were on either no treatment or monotherapy and recruited from ten Australian clinics between 2017 and 2020. Half had a treatment approach that began with the quadpill, while half began with a single blood pressure lowering drug at normal dose.

The research team modelled the costs and benefits of lifetime treatment, including estimates of costs of medications and of predicted cardiovascular events in both groups. They found a quadpill would likely be cost effective to the Australian health system within a range of scenarios and for different kinds of patients.

The results showed:

  • The average cost per person at 12 weeks in the quadpill group was $342 and in the monotherapy group was $277, a difference of $65
  • Compared to usual care, the improved blood pressure reduction in the quadpill group was predicted to reduce lifetime incidence of heart attack and stroke, and cost about $14,000 per extra healthy life year
  • In people with medium or high cardiovascular risk in particular, it was projected the quadpill would cost less and be more effective than usual care.

“We found that the greatest benefit of combination therapy is in comparison to usual care, where clinical inertia means patients are not being moved onto combination therapy to achieve more effective blood pressure control,” said Dr Atkins.

The study also incorporates savings anticipated from Australia’s new 60-day dispensing policy, which will come into effect for blood pressure medications in September.

“If we extend this to a model for 90-day dispensing, the cost effectiveness of a quadpill would come down further to about $2,000 per extra healthy life year; and if a quadpill were available for less than 45 cents a day, it would achieve further savings and be more effective than usual care.

“Although the quadpill is not currently manufactured, we know from the QUARTET study - the first large-scale Australian trial using combinations of very low-doses in one capsule and first to show the benefits are maintained to 12 months without any reduction over time - that this strategy significantly improves control of high blood pressure, the leading cause of heart attack and stroke, compared to usual treatment,” Dr Atkins said.

“Our study strongly indicates that a quadpill could represent a promising treatment option to help Australians with high blood pressure achieve sustained control and reduce their risk of further health consequences in an affordable way. The strategy of treating with a quadpill from the outset also challenges the status quo and has implications for clinical guidelines and practice,” she said.


  1. Heart publication - doi link and citation details when available
  2. Chow CK, Atkins ER, Hillis GS, Nelson MR, Reid CM, Schlaich MP, Hay P, Rogers K, Billot L, Burke M, Chalmers J, Neal B, Patel A, Usherwood T, Webster R, Rodgers A. Initial treatment with a single-pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a randomised, double blind active-controlled clinical trial. The Lancet. 2021;398(10305):1043-52