Scientists have long known that people living with HIV face a higher risk of heart disease. The statin drug pitavastatin, however, might offer a solution.
In a phase 3 clinical trial, individuals with an HIV infection who took pitavastatin – a medication 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 on Sunday in The New England Journal of Medicine and presented at a meeting of the International AIDS Society in Brisbane, Australia.
The report offers a promising new way for individuals 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 – diseases. While there is no cure, treatment with antiretroviral medications can help individuals manage the disease and lead near-normal lives.
People with HIV, however, face up to double the risk of heart disease and cardiovascular complications compared to the general population, said Dr. Patrice Desvigne-Nickens, a physician at the National Heart, Lung, and Blood Institute’s Division of Cardiovascular Sciences, who worked on the trial. Heart complications happen much earlier – and are deadlier – for people with HIV.
While scientists aren’t sure exactly why, experts believe it could be a consequence of high, persistent inflammation and chronic immune activation from HIV.
“This is becoming a major issue for the HIV community,” said Dr. Steven Grinspoon, a professor of medicine at Harvard Medical School and the study’s lead author. “They’re still having heart attacks and strokes, despite being on good, effective antiretroviral therapies. They’re not having HIV-specific comorbidities; they’re having heart disease.”
Named the REPRIEVE trial, the study recruited more than 7,700 participants worldwide between the ages of 40 and 75, all of whom had HIV, were currently taking antiretroviral medication, and were rated to have a 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 the patients nor their treating physicans knew which one they were getting.
Pitavastatin belongs to a class of pharmaceuticals called statins that reduce the amount of cholesterol made by the liver and help the liver break down cholesterol in the blood. As a result, the drug lowers the low-density lipoprotein (LDL) cholesterol – or “bad cholesterol,” as Desvigne-Nickens described it – that 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, making it “amazingly perfect,” according to Desvigne-Nickens. The medication is also widely available at “relatively cheap” prices, Grinspoon noted.
Pitavastatin, however, isn’t typically given to patients with a “low-to-moderate” risk of heart disease, like people with HIV might be. The American Heart Association and American College of Cardiology’s standard risk-assessment, which includes criteria such as age, sex and ethnicity, don’t include HIV-related cardiovascular risk factors, either.
That omission creates a blind spot for patients with HIV who score lower on the risk assessment and aren’t prescribed pitavastatin, but still have a disproportionately high rate of heart conditions.
“They wouldn’t typically be recommended a primary prevention drug strategy because the risk is in the low to moderate range because there’s been no data,” said Grinspoon. “This is where REPRIEVE fits in very nicely.”
In the trial, the researchers found that HIV-positive patients taking pitavastatin were about 35% less likely to experience an “adverse” cardiovascular event, like a heart attack, than the control group. They also observed 21% fewer events of cardiovascular events and death in patients, said Desvigne-Nickens.
If pitavastatin was just lowering LDL cholesterol levels, though, there should only have been a 17% decrease in cardiovascular risk, Grinspoon calculated – less than half of the risk reduction in the trial.
As a result, the report suggests that statin therapy does more than reduce LDL levels; it also reduces the immune activation and inflammation that puts 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. Across the board, the researchers found a consistent reduction in cardiovascular risk.
For Desvigne-Nickens, it was a “slam dunk.”
“This is unbelievably 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 stopped early, after about five years per participant. After looking at the data ¾ of the way through the REPRIEVE trial, she explained, an independent safety board had enough data to know that the drug was “very effective”– more so than was expected beforehand.
“This 35% reduction was so compelling that they could stop the trial,” Desvigne-Nickens said. “They knew the answer. They knew this drug was very effective in reducing these adverse cardiac events.”
“That’s typically only done when the results are very robust,” Grinspoon added.
Participants taking pitavastatin also developed diabetes, a known side effect of the statin drugs, at a slightly higher rate: 5% vs. 4% in the control group. Pitavastatin was also equally efficacious at reducing cardiovascular risk for patients with diabetes, Grinspoon noted.
He suspects that many physicians will begin incorporating the findings into their clinical practice. And he’s hopeful that the findings will prompt regulatory bodies to consider incorporating pitavastatin into standard care for people living with HIV.
“It’s extremely generalizable and rigorous in terms of its randomized, placebo-controlled, double-blind design,” he said. “And I think based on the large group it covers, it will be considered important enough to incorporate into guidelines. I think the community will agree that these guidelines will be incorporated.”
The researchers’ optimism stems from the diverse scope of the trial. The study was conducted across twelve countries, including several in sub-Saharan Africa, Asia, South America and the Caribbean, with a high burden of HIV.
Thirty percent of the study’s participants were women, and 65% were not White – a striking comparison, Grinspoon explained, to research that has historically neglected those populations.
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“We thought it was important to get even more global and diverse in our trial,” he added. “It’s really a global trial. Now we can say this is a great trial for all these other groups into as well.”
For individuals taking antiretroviral medication, the researchers also hope that pitavastatin doesn’t add too much of a burden. As a daily medication that’s accessible and affordable, it could be an easier addition to the medication routine of someone with HIV, who might already have “complicated drug medical regimens,” according to Desvigne-Nickens.
“We’re showing that the addition of a single pill a day on top of antiretroviral therapy will prevent heart disease,” Grinspoon said. “Now we have evidence for those people who would typically not be recommended anything: that something does work.”