26 August 2019

Could the polypill become a reality?

Cardio Clinical Research

A world-first study has proven that the polypill is safe and effective for CVD prevention, but plenty of hurdles remain, an Australian expert says.

The polypill was dreamed up almost 20 years as a way to make CVD prevention easier and cheaper for patients, particularly those in low- and middle-income countries.

It’s a four-in-one tablet, taken daily, that contains aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan.

It had been difficult to put the polypill to the test because it wasn’t a big money-maker for generics manufacturers, Professor Anushka Patel, a cardiologist and scientist at The George Institute for Global Health, said.

However, in a “monumental effort by a dedicated research team” from Iran, the first large-scale trial of the polypill had finally been done, she said.

The randomised five-year study of around 6,800 people, published recently in The Lancet, found that people taking the polypill were 34% less likely to have a major CVD event than people just receiving lifestyle advice.

Doctors would need to treat around 35 people with the polypill for five years to prevent one major CVD event, the research showed.

The study recruits were aged 50 to 75 years and were mostly from the rural villages in the Golestan province of Iran. Around 90% had no history of CVD and half were women.

Dropout rates were low, with around 80% of patients continuing to take the polypill during the study.

(By comparison, previous research has shown that a third of US patients stop taking preventive medication as early as 90 days after having a heart attack.)

“A fixed-dose polypill strategy could help achieve the UN Sustainable Development Goal to reduce premature mortality due to cardiovascular disease by at least a third before 2030,” the researchers said.

Professor Patel said it was likely that the effects of the polypill on CVD events “might be more modest than reported” in the study.

One of the reasons for this was the lack of doctor blinding at the start of the trial. The researchers only started using blinding when it became clear that patients were not being allocated to treatment arms randomly.

The polypill also didn’t appear to have much effect on blood pressure or LDL cholesterol in the study, which are known risk factors for CVD events.

“Our trial participants were relatively healthy and most had normal blood pressure, so this small decrease in blood pressure was not unexpected,” the authors said.

The main downside to the polypill was the fixed dose, which meant that doctors couldn’t individualise treatment, Professor Patel said.

However, the Iranian study showed that the polypill could cut CVD events without increasing adverse events.

“There is a role for the polypill,” she said. “The next steps are going to be around how do you get this through the regulatory pathway. You need to convince the regulators that this is going to be effective and safe.

“The regulators will accept this latest data, but they’ll be interested in whether the combined tablets work the same as giving four separate medications.

“So, they are the type of regulatory trials we need to do, which are much smaller, easier to do than these big, large-scale trials.”

The Lancet 2019, 24 August