Four-in-one pill 'effective' for high blood pressure

"Four-in-one 'miracle' pill to cure high blood pressure," is the headline on Mail Online.

This is based on early research from Australia looking at the effect of a four-in-one "quadpill" on high blood pressure.

The idea behind the quadpill is that by combining four hypertension drugs at a much lower dose than they are normally used, you still get a beneficial effect, but you minimise the risk of side effects.

In a small study involving only 18 people, the quadpill was compared to placebo (a dummy treatment).

While they were taking the drug all 18 people had a greater reduction in blood pressure compared with when they were taking the placebo.

While the prospect of a blood pressure-lowering drug with fewer side effects is exciting, it is important to remember that this was a very small study.

As only 18 people took the drug for just four weeks, and the quadpill was not compared to full strength blood pressure pills, we don't know yet if it is a "miracle" or just a useful option.

All adults over 40 are advised to have their blood pressure checked at least every five years. Getting this done is easy and could save your life.

Where did the story come from?

The proof-of-concept study was carried out by researchers from various institutions across Australia, including the University of Sydney, as well as John Hopkins Bloomberg School of Public Health, US, and Imperial College, UK.

The study was published in the peer-reviewed medical journal The Lancet.

The study was funded by various sources, including National Health and Medical Research Council (NHMRC) fellowships and a range of pharmaceutical companies. The authors declare the funder had no role in any aspect of the study.

The UK's media generally reported the story accurately, if a little overexcitedly. The Sun's report that the drug was "100 per cent effective at tackling high blood pressure" is a bit misleading, as blood pressure was reduced to a controlled level on just one measure.

And Mail Online's claim that this was a "miracle drug" is hyperbolic.

The idea that this was early exploratory research seemed to be largely overlooked by the media.

What kind of research was this?

This was a randomised controlled trial (RCT) of patients who had untreated moderate to high blood pressure, aiming to see if a combination pill – quadpill – of four blood pressure-lowering drugs (each at a lower dose than normal) would be effective and safe, compared to a placebo drug.

An RCT is good as you can see the effects of an intervention – in this case the quadpill – on reducing blood pressure.

As a crossover trial, everyone had the chance of receiving four weeks of treatment and four weeks of placebo (with a two-week break in between), without evaluators being aware of the order treatment was given

The researchers also included a systematic review of the literature in order to look at the existing studies into effectiveness of just one blood pressure drug given at a quarter strength. This was useful in judging whether theirs was a one-off finding and to see what the average side-effect rates for the component drugs compared to a placebo were.

What did the research involve?

Researchers randomised 21 adults, of whom 18 completed the trial. These people had untreated high blood pressure. They carried out a double-blind randomised controlled trial, comparing a quadpill (a pill containing four blood pressure reducing drugs, each at a quarter of their usual strength) and a placebo.

The participants were randomly allocated to either the quadpill or a placebo for four weeks. This treatment was followed by a two-week "washout" (no pill taken), then the other treatment was taken for four weeks (participants taking placebo for the first four weeks took the quadpill for the final four weeks and vice versa).

At four weeks, the researchers looked at the reduction in mean 24-hour systolic blood pressure (the highest pressure when your heart beats and pushes blood around your body) while carrying out normal daily activities.

They also looked at reduction in mean 24-hour diastolic blood pressure (the lowest pressure when your heart relaxes between beats), as well as daytime and nighttime diastolic blood pressure, at four weeks.

Blood pressure recorded in the researchers' office was also examined.

Controlled blood pressure was considered to be less than 135/85mm Hg for the 24-hour blood pressure, and less than 140/90mm Hg for office blood pressure.

Researchers also looked at adverse events of taking the quadpill compared to placebo.

A systematic review was also done, looking at the effectiveness and side effects of taking either one or two blood pressure-reducing pills (rather than four) at a quarter of the usual strength, compared to a placebo.

What were the basic results?

24-hour blood pressure less than 135/85mm Hg (the threshold for controlled blood pressure) was achieved by 15 of 18 participants on the quadpill compared with seven of 18 on placebo (relative risk [RR] 2.14, 95% confidence interval [CI] 1.25 to 3.65).

All 18 participants achieved office systolic and diastolic blood pressure less than 140/90mm Hg (the threshold for controlled blood pressure) while on the quadpill, compared with six of 18 on placebo (relative risk 3.01, 95% confidence interval (CI) 1.54 to 5.89).

  • The difference in mean 24-hour systolic blood pressure between quadpill and placebo was 18.7mm Hg (95% (CI) 14.3 to 23.0).
  • The difference in mean 24-hour diastolic blood pressure between quadpill and placebo was 14.2mm Hg (95% CI 11.5 to 16.9).
  • The difference in mean office systolic blood pressure between quadpill and placebo was 22.4mm Hg (95% CI 16.5 to 28.3).
  • The difference in mean office diastolic blood pressure between quadpill and placebo was 13.1mm Hg (95% CI 8.9 to 17.3).

There were no serious adverse events reported.

The systematic review found 36 trials with one drug at a quarter dose and six trials of two drugs at a quarter dose, against a placebo. No increase in side effects was found compared with a placebo, indicating the advantages of a single pill with low doses of multiple blood pressure-lowering drugs.

How did the researchers interpret the results?

The researchers conclude that "the findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure".

They add that "further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer-term tolerability".


The findings of this early-stage study suggest that a quadpill might be an effective way of lowering blood pressure. It might also show fewer side effects associated with taking blood pressure tablets at higher doses, such as dizziness, diarrhoea, or a cough.

There are some limitations to the study:

  • There were only 18 people included in the study. A bigger trial needs to be undertaken to find out what the results would look like if the quadpill was widely used in the population.
  • The study was undertaken in an Australian setting where medication and monitoring of blood pressure might differ – therefore results might not be generalisable to other settings.
  • People in the study took the quadpill for just four weeks. The medication needs to be taken for longer in order to see long-term effectiveness and possible side effects.
  • The "controlled" level of blood pressure the researchers used did not mean that participants had an ideal blood pressure, just that their blood pressure was no longer considered high.

This is an early-stage trial. Changes to advice on blood pressure medication won't happen immediately, but this approach appears to be promising and further larger trials, hopefully against existing single therapies, could provide stronger evidence.

Ways you can combat high blood pressure, as well as other chronic diseases, include:

Read more about preventing high blood pressure.

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