Primary prevention of cardiovascular disease important in people with HIV

People living with HIV have a significantly increased risk of cardiovascular disease that requires a different level of preventive management than in the general population.

Last year, an HHS panel released recommendations for the use of statin therapy as primary prevention of atherosclerotic cardiovascular disease (ASCVD) in people with HIV. Researchers are continuing to explore whether other agents, such as anti-inflammatory drugs, may reduce such risks, and how to manage the higher risk of heart failure in this population, which statins cannot address.

New Recommendations for Statins in People With HIV

New clinical guidelines published in May described in more depth the justification for the statin recommendations, the evidence behind them, and the remaining gaps in research.

The recommendations are primarily for people ages 40-75 who have HIV and a low to intermediate risk of ASCVD, defined as less than 20% over 10 years. Those with at least a 5% risk should take moderate-intensity statins, including 4-mg daily pitavastatin (Livalo), 20-mg daily atorvastatin (Lipitor), or 10-mg daily rosuvastatin (Crestor).

Matt Durstenfeld, MD, of the University of California San Francisco, who specializes in cardiovascular health for people with HIV, told MedPage Today that it’s worth considering a high-potency statin in those with greater than a 5% risk, though the guidelines only call for at least a moderate-intensity statin.

The recommendations are based on the results of the REPRIEVE trial, which showed a 35% reduced risk of any major adverse cardiovascular event (MACE) over 5 years with pitavastatin versus placebo in patients with HIV and a low to moderate risk of cardiovascular disease.

“REPRIEVE took a lot of the ambiguity out and made it really clear that there is a benefit of treating people with HIV who were previously considered borderline,” Durstenfeld said.

Craig Beavers, PharmD, of the University of Kentucky in Lexington and the lead author of the guidelines, told MedPage Today that many clinicians may have thought that people with HIV cannot take statins because protease inhibitors, a mainstay of several antiretroviral therapy (ART) regimens, have a lot of drug interactions. But pitavastatin doesn’t have those interactions, and many patients with HIV are now on different ART regimens without a protease inhibitor. The guidelines include a table to help clinicians navigate statins and drug-drug interactions with various ART regimens.

Patients over age 40 with a greater than 20% ASCVD risk should follow the recommendations for the general population, taking a high-intensity statin. For people with HIV who are under 40, not enough data exist to guide statin recommendations for primary prevention. In these situations, the patient and clinician should discuss the risks and benefits for that particular patient, given their personal risk factors, lifestyle, and preferences, Durstenfeld said.

“You may have other information that can help inform the personalized risk calculus,” he said.

Beavers noted that the decision may also depend on management of their HIV. “If their HIV is well controlled and their viral load is down, the risk could be lower versus someone who has had an uncontrolled or continuously uncontrolled viral load,” he said.

An important nuance to understand about the REPRIEVE trial and new guidelines, Durstenfeld added, is that they are based on the 2013 American College of Cardiology (ACC) ASCVD risk calculator, not the newer American Heart Association PREVENT calculator that a growing number of clinicians have switched to using.

“It really matters which calculator you’re using because different calculators will predict a different 10-year risk,” Durstenfeld said. “You can’t just use the same threshold with the new calculator.”

For the purposes of these guidelines, clinicians should use the 2013 ACC calculator, he said, but they also need to be aware that this calculator, like all current general population cardiovascular calculators, underestimates risk in people with HIV.

Beavers said the guidelines also describe some of the gaps that require further research to better understand cardiovascular risk in people with HIV, particularly as it relates to those under 40.

“We don’t have an understanding of what lifetime prevention would look like,” Beavers said. “We know, historically, when we had less control of HIV, the risk for cardiac events would go up, but in patients that are younger or able to get screened and treated earlier, is their risk burden the same? And do we need to follow the same primary prevention guidelines?”

It will take more research to find out, he added.

Understanding Overall Increased Cardiovascular Risk With HIV

The higher cardiovascular risk in people with HIV includes all types of heart conditions, not only ASCVD, but also heart failure, arrhythmias, and cerebrovascular disease, including stroke, peripheral vascular disease, venous thromboembolism, pulmonary hypertension, and aortic aneurysms. Risk of atrial fibrillation is approximately 1.5 times greater in those with HIV, especially those with viremia or low CD4 counts, and risk of heart failure is 1.5 to 2 times greater.

“One common way I explain this is that people with HIV get heart disease 10 years earlier,” Durstenfeld said. “That really puts it into perspective for some people.”

In terms of relative risk, incidence of cardiovascular disease is over twice as high in those with HIV compared with those without HIV, and prevalence among people with HIV has tripled in the last 20 years, as noted in a review of cardiovascular disease in people with HIV that Durstenfeld authored.

“Some of that has to do with increased burden of traditional risk factors,” such as a higher prevalence of smoking, lower activity levels, hypertension, and obesity, among those with HIV, Durstenfeld said, though he added that the higher risk is not entirely explained by traditional factors.

“Other things we think about are chronic inflammation that may result from the time before they were treated, or it may relate to ongoing inflammation from the viral reservoir in the tissues, even if there’s no detectable virus in the blood, or from co-infections or increased gut permeability that increase chronic inflammation,” he explained.

It’s also possible that effects from ART play a role, since several regimens can adversely affect lipid levels. While the newer integrase strand transfer inhibitor regimens have more favorable effects on lipids, they are also associated with more weight gain.

“The cardiometabolic effects of ART must be weighed against selecting the most effective antiviral with high genetic barrier to resistance,” Durstenfeld and his co-author wrote in their review. “In most cases, lipid abnormalities should be managed directly with statins rather than switching ART regimens.”

For those who cannot take statins or remain at high risk despite statin use, other therapies to consider include PCSK9 inhibitors, ezetimibe (Zetia), and bempedoic acid, Durstenfeld said. For atrial fibrillation, dabigatran (Pradaxa) has the fewest drug-drug interactions with ART regimens, while the calcium channel blockers diltiazem and verapamil have interactions with older ART regimens.

A number of unanswered questions remain about the best way to manage primary prevention of heart disease in people with HIV, Durstenfeld said. One of those questions is whether aspirin should be used as a primary prevention strategy in this population. Another is whether various other anti-inflammatory agents have any benefits, such as colchicine. And while there are no drug-drug interactions with standard heart failure medications, gaps in prevention exist there as well.

“There’s still a lot of need to understand what leads to heart failure in people with HIV, if there are HIV-specific factors [that contribute to it], and what we can do to lower those risks too,” he noted.

By Tara Haelle