‘Quadpills’ for high blood pressure more effective than one medicine alone

10 October 2021

An important new study published in The Lancet this September has shown that treatment with a ‘quadpill’ containing four different blood pressure medicines, each at a quarter of the usual dose, lowers blood pressure more effectively than starting with one blood pressure medicine and building up. The QUARTET study adds weight to a growing body of research supporting combination pills containing different blood pressure medicines and the authors argue this should inform future guidelines.

 

How the study worked

Researchers based in Australia split 591 adults with high blood pressure into two groups. One group (the control group) received one blood pressure tablet at a standard dose, which is how blood pressure is often treated, and the other group received a combination ‘quadpill’ containing four different medicines at a quarter of the usual dose. If blood pressure was not brought down to target, the clinician could add additional medicines (known as ‘uptitration’).

After 12 weeks, more people in the quadpill group had their blood pressure under control (76% vs 58%) and their blood pressure was lowered by an average of 6.9mmHg more than those in the monotherapy group. After one year, a subgroup of patients were still taking part in the study and the effect was maintained: more people had their blood pressure under control in the quadpil group (81% versus 62%) and systolic blood pressure (the top number) was 7.7mmHg lower than in the control group.

Also of note was that more people in the control group needed extra medicines prescribed by their physician - most people in the intervention group didn’t need any further medicines at all. By 12 weeks, 40% in the control group were given additional medications compared to only 15% of those taking the quadpill. After one year, more people in the control group were having uptitration yet they never caught up with the quadpill group in terms of blood pressure control.

Importantly, there was no difference in side effects between the two groups.

 

What this study adds

Previous studies have already shown potential for a quadpill but they were smaller, short term, and didn’t look at adverse effects (side effects). They also didn’t explore the possibility of adding medicines (‘uptitration’) if the first dose wasn’t enough.

This study addresses these issues, demonstrating a sustained benefit with the quadpill over a year with no difference in side effects, and less need for uptitration. It’s also the first study to show that starting with one medicine and adding to it over time does not achieve ‘catchup’ over 12 months. 

The percentage of people to have their blood pressure brought under control (to less than 140/90mmHg) was also higher than those seen in previous trials of combination tablets: 76% after 6 months and 81% after 12 months.

High blood pressure is extremely common, affecting 1.28 billion people worldwide, and the leading modifiable cause of disease burden globally. Treatment often starts with monotherapy (one blood pressure medicine) and if this doesn’t bring blood pressure down to target, more medicines are added. Often multiple medicines are needed, which work by lowering blood pressure in different ways.

There are some challenges to taking blood pressure medicines to their best effect and blood pressure often remains uncontrolled. One challenge is adherence from the patient, whereby people don’t take their medicines every day as prescribed, and this seems to get worse the more medicines people have to take. Another problem is ‘inertia’ from the clinician, where the clinician doesn’t intensify treatment when the patient’s blood pressure target isn’t reached, which is what the authors of this study were interested in. 

Some guidelines around the world are already recommending combination medicines to overcome these challenges, and this study adds support to these guidelines. 

 

Limitations of this study

The study has some limitations. For example, it was smaller than planned due to COVID-19 restrictions which means the results aren’t as strong as if larger numbers had been involved. The clinicians who took part had lower rates of treatment inertia than usually observed, meaning the benefits seen may be an underestimate.

 

Conclusions
This study showed that starting with a single tablet that contained a fixed dose of four different medicines at a quarter of the usual dose achieved better blood pressure control than the common strategy of starting with one blood pressure medicine at a higher dose. Importantly, there was no higher risk of side effects.

The quadpill lowered blood pressure by an extra 7mmHg on average compared to the usual monotherapy. If maintained in the long term, this would translate to an estimated extra 11% lower risk of ischemic heart disease and 18% lower risk of stroke and heart failure.

The authors stated that clinical practice guidelines should incorporate evidence on low-dose combination pills and said “This new paradigm holds promise for achieving better blood pressure control for people with hypertension around the world.”

Professor Graham MacGregor, Chairman of Blood Pressure UK says: “Despite effective treatments being available, many people receiving treatment for high blood pressure don’t have their blood pressure under control. The QUARTET study supports the use of low-dose combination pills as a simple option to avoid the time-consuming step-by-step process of starting with one medicine and adding more and more. It also avoids the side effects of higher doses which are a concern to doctors and patients alike.

“As quadpills are so simple, they could be a great advantage to countries with fewer resources as well as in wealthier nations. We support the inclusion of low dose combination pills in treatment guidelines.”