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Heart polypill cuts cardiovascular disease risks by 21% over placebo in primary prevention trial

New England Journal of Medicine
AHA 2020
Reuters Health - 13/11/2020 - A new test of a multi-drug pill containing a statin and three blood pressure medicines shows that long-term use can lower cardiovascular disease risks for people with no previous history of heart disease or stroke by 21%.

Adding low-dose aspirin to the mix cuts the odds by 31%.

The pill used in the 5,713-patient TIPS-3 study contained simvastatin, atenolol, hydrochlorothiazide and ramipril.

For the primary outcome of a major cardiovascular event plus heart failure, resuscitated cardiac arrest or arterial revascularization, the rate after a mean follow-up of 4.6 years was 4.4% in the polypill group and 5.5% among placebo recipients (95% confidence interval of 0.63 to 1.00).

When 75 mg of aspirin was added to the daily treatment, the rates were 4.1% with the polypill and 5.8% in the control group (0.50 to 0.97).

"There was a similar effect on death from cardiovascular causes, myocardial infarction or stroke," said the research team, led by Salim Yusuf, a professor of medicine at McMaster University in Ontario, Canada.

The findings were presented Friday at the American Heart Association (AHA) Scientific Sessions meeting and released online by the New England Journal of Medicine.

The study also hinted at a benefit of low-dose aspirin alone.

In the subset of volunteers who only used aspirin or placebo, the rate of death from cardiovascular causes, heart attack or stroke was 4.1% with aspirin versus 4.7% with placebo, a 14% reduction (95% confidence interval of 0.67 to 1.10). There were 1,431 patients in that group.

The patients - treated at 86 centers in nine countries, with more than two thirds living in India or the Philippines - were selected because they had elevated risk based on the 49-point INTERHEART Risk Score, but no known cardiovascular disease. The men were age 50 and older; the women were age 55 and older.

Dr. Yusuf told Reuters Health in a telephone interview that doctors and patients often have trouble juggling multiple medications, with physicians often adjusting the dose of one drug at one time. An effective multi-drug pill would make compliance and prescribing easier.

His team found that the combined outcome of death from cardiovascular causes, heart attack or stroke was 3.9% with the polypill and 4.9% with placebo (with a 95% confidence interval of 0.61 to 1.01).

Polypill treatment lowered LDL cholesterol by about 19 mg per deciliter and systolic blood pressure by about 5.8 points.

The risk of hypotension or dizziness severe enough to cause temporary or permanent discontinuation of the trial was 2.7% with the polypill and 1.1% with placebo.

Compliance was above 67% at the two-year mark. The discontinuation rate was about double the 20% originally anticipated, in part due to the pandemic, the researchers said.

Aspirin use did not increase the risk of bleeding. However, the study had a run-in period that excluded people who showed significant side effects, and 9.5% of volunteers did not participate for that reason.

The combination used in the study "is one of the first polypills," Dr. Yusuf said. "Our study was a concept study. There will be better polypills that groups will produce."

Most drug companies are unlikely to push for them because the pills use generic medicines, so the potential profit margin is low. "It's unrealistic to expect big pharma to put in this money. It's a fact of life," he said.

"This is where government can step in," he said. The COVID-19 pandemic is showing that the government can make a difference, he said, and it should also get involved in addressing "a chronic epidemic that is killing 18 million people a year."

No such pills are available in the United States and Canada. But Dr. Yusuf said he knows of at least three such products in Europe.

Polypill use is not widespread there, but that's because convincing data are only now emerging to show that such pills can have an impact on prevention, he said.

By Gene Emery

SOURCE: https://bit.ly/2IBokZg The New England Journal of Medicine, online November 13, 2020.

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