Cholesterol lowering drugs reduce risk of heart disease in people with HIV, trial finds

CNN
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Scientists have long known that people living with HIV are at a higher risk of heart disease. The statin the drug pitavastatin, however, might offer a solution.

In a phase 3 clinical trial, people with HIV who took pitavastatin – a drug used to lower high cholesterol – were 35% less likely to suffer major heart complications, including heart attacks, heart failure or strokes. The findings were published in the New England Journal of Medicine on Sunday and presented at a meeting of the International AIDS Society in Brisbane, Australia.

The report offers a promising new way for people living with HIV to better manage their heart health.

HIV, or human immunodeficiency virus, attacks and weakens the body’s immune system, leaving patients vulnerable to other, often fatal, illnesses. Although there is no cure, treatment with antiretroviral drugs can help individuals manage the disease and lead near-normal lives.

People living with HIV, however, are at double the risk of heart disease and cardiovascular complications compared to the general population, said Dr. Patrice Desvigne-Nickens, a physician in the Division of Cardiovascular Sciences at the National Heart, Lung and Blood Institute, who worked on the trial. Cardiac complications occur much earlier – and are more deadly – ​​for people living with HIV.

Although scientists aren’t exactly sure why, experts believe it could be a consequence of persistent high inflammation and chronic immune activation due to HIV.

“This is becoming a major issue for the HIV community,” said Dr. Steven Grinspoon, professor of medicine at Harvard Medical School and lead author of the study. “They continue to have heart attacks and strokes, despite receiving good, effective antiretroviral treatment. They have no HIV-specific comorbidities; they have heart disease.

Called the REPRIEVE trial, the study recruited more than 7,700 participants worldwide between the ages of 40 and 75, all of whom were HIV-positive, currently taking antiretroviral drugs, and were at low to moderate risk of heart disease.

Each participant was randomly assigned to take a daily dose of pitavastatin or a placebo tablet. In this double-blind setup, neither patients nor their treating physicians knew which one they were receiving.

Pitavastatin belongs to a class of pharmaceuticals called statins which reduce the amount of cholesterol produced by the liver and help the liver break down cholesterol in the blood. As a result, the drug lowers low-density lipoprotein (LDL) cholesterol — or “bad cholesterol,” as Desvigne-Nickens described it — which can build up inside blood vessels and cause heart problems.

It was specifically chosen for the HIV trial because it doesn’t interact with antiretroviral drugs, which makes it “incredibly perfect,” according to Desvigne-Nickens. The drug is also widely available at “relatively cheap” prices, Grinspoon noted.

However, pitavastatin is generally not given to patients at “low to moderate” risk of heart disease, such as people living with HIV might be. The American Heart Association and American College of Cardiology standard risk assessment, which includes criteria such as age, gender and ethnicity, also does not include HIV-related cardiovascular risk factors.

This omission creates a blind spot for HIV-positive patients who score lower on the risk assessment and are not prescribed pitavastatin, but still have a disproportionately high rate of heart disease.

“They would generally not be recommended as a primary drug prevention strategy because the risk is low to moderate because there are no data,” Grinspoon said. “That’s where REPRIEVE fits in really well.”

In the trial, researchers found that HIV-positive patients taking pitavastatin were about 35% less likely to experience an “adverse” cardiovascular event, such as a heart attack, than the control group. They also observed 21% fewer events of cardiovascular events and deaths in patients, Desvigne-Nickens said.

If pitavastatin only lowered LDL cholesterol, there should have been only a 17% decrease in cardiovascular risk, Grinspoon calculated – less than half the risk reduction in the trial.

Accordingly, the report suggests that statin therapy does more than reduce LDL levels; it also reduces immune activation and inflammation that put HIV-positive people at risk for heart disease in the first place.

And among different subgroups, including women and international populations, the researchers found that the therapeutic benefit was the same. Overall, the researchers found a consistent reduction in cardiovascular risk.

For Desvigne-Nickens, it was a “slam dunk”.

“It’s incredibly positive,” Desvigne-Nickens said. “It was almost too good to believe that the drug exceeded expectations.”

So much so, in fact, that the study was terminated prematurely, after about five years per participant. After reviewing data from ¾ of the REPRIEVE trial, she explained, an independent safety committee had enough data to know that the drug was “very effective” – ​​more than previously expected.

“That 35% reduction was so compelling that they were able to stop the trial,” Desvigne-Nickens said. “They knew the answer. They knew that this drug was very effective in reducing these adverse cardiac events.

“It’s usually only done when the results are very robust,” Grinspoon added.

Participants taking pitavastatin also developed diabetes, a known side effect of statins, at a slightly higher rate: 5% versus 4% in the control group. Pitavastatin was also equally effective in reducing cardiovascular risk in diabetic patients, Grinspoon noted.

He suspects that many physicians will begin to incorporate the results into their clinical practice. And he hopes the results will prompt regulators to consider integrating pitavastatin into standard care for people living with HIV.

“It is extremely generalizable and rigorous in terms of its randomized, placebo-controlled, double-blind design,” he said. “And I think based on the large group that it covers, it will be considered important enough to incorporate into the guidelines. I think the community will be okay with these guidelines being incorporated.

The researchers’ optimism stems from the diverse scope of the trial. The study was conducted in twelve countries, including several in sub-Saharan Africa, Asia, South America and the Caribbean, where the burden of HIV is high.

Thirty percent of study participants were female and 65 percent were non-white — a stark comparison, Grinspoon said, with research that has historically overlooked these populations.

“We thought it was important to be even more comprehensive and diverse in our trial,” he added. “It really is a world trial. Now we can say that it’s also a big trial for all these other bands.

For people taking antiretroviral drugs, the researchers also hope pitavastatin won’t add too much of a burden. As an accessible and affordable daily medication, it could be an easier addition to the medication routine of someone living with HIV, who might already have “complicated medical regimens,” according to Desvigne-Nickens.

“We show that adding just one pill a day in addition to antiretroviral therapy will prevent heart disease,” Grinspoon said. “Now we have evidence for people for whom nothing would generally be recommended: that something works.”