Cardiometabolic Considerations

CE / CME

Individualizing ART With Cardiometabolic Considerations

Nurses: 0.75 Nursing contact hour

Pharmacists: 0.75 contact hour (0.075 CEUs)

Physicians: maximum of 0.75 AMA PRA Category 1 Credit

Released: July 10, 2024

Expiration: July 09, 2025

Grace A McComsey
Grace A McComsey, MD

Activity

Progress
1 2
Course Completed

What is the CV risk for women with HIV? What do we know about statin benefits with low ASCVD risk estimates?

Our case patient has a CVD risk estimate of 4%. Does that mean she is low risk? Does it mean I should not worry about her? The results of the REPRIEVE study with statins indicate that this is not an easy answer.

REPRIEVE: Statins for Cardiovascular Disease Prevention in People Living With HIV

The REPRIEVE study was a global, randomized, placebo-controlled trial with more than 7000 participants.13,14

This study assessed the effect of a statin in people with HIV on stable ART and low to moderate CVD risk. Investigators asked whether people on pitavastatin 4 mg once/day would experience a reduction in CV events compared with people taking placebo. This was the first study looking at CV events as an outcome. Prior studies, including the one I did, looked only at markers of CVD, but REPRIEVE looked at events.

After a median of 5.1 years follow-up, the study was stopped early because of the big difference in major adverse cardiovascular events between the pitavastatin and placebo arms.

As shown on the slide, the effect was consistent across subgroups, (ie, between females and males, and different ages), including different CV risk factors.

REPRIEVE: First Major Cardiovascular Event by ASCVD Risk Score

This slide shows that pitavastatin was effective overall and in all atherosclerotic cardiovascular disease (ASCVD) risk score groups. As shown on the right, for people in the group with a CVD risk of 5% or higher, the number of people needed to treat (NNT) to avoid 1 major CV event would be between 35 and 53.  If people had a lower CVD score, between 0 and 5%, between 149 and 199 people must be treated to prevent 1 CVD event. In the cardiology world, that is still acceptable.

Overall, regardless of the CVD risk estimate calculation, statins were effective, although you need to treat more people when the CVD risk score is less than 5%.13,14

Updated DHHS Recommendations for Statins for People Living With HIV: February 27, 2024

Thanks to the results of the REPRIEVE study, new guidelines were recently issued for statin use in people living with HIV.2 I was a part of this guideline committee, and we reviewed all statin data in HIV and compared it with data from the general population and to other populations.

Also of note is that, in people on placebo, the study showed that the CVD risk calculation underestimated the observed CV events rates in people living with HIV. This may be because HIV induces sustained levels of systemic inflammation and other factors pertinent to HIV that the risk score calculation does not account for. Basically, when you see a 4% ASCVD risk score in a person with HIV, it is probably much higher.

In our analysis, we came up with the simple recommendation that people with HIV aged 40 to 75 years who have a low to intermediate 10-year CVD risk between 5% and 20%, should receive at least moderate intensity statin therapy. We selected this age range because this is the age of people studied in REPRIEVE, but it does not mean that someone who is 39 or 76 years of age would not qualify.

The statin options include pitavastatin, which was used in the study, but if pitavastatin is difficult to get in clinic, atorvastatin and rosuvastatin are good choices.

Of note, the intensity of the statin refers to the level of decrease in LDL cholesterol. For example, a moderate-intensity statin taken at the recommended doses will decrease LDL cholesterol by >30%. High-intensity statins will decrease LDL cholesterol by more than 50%.

Now, what happens if the CV event risk is <5%? There is still a benefit, but as we discussed earlier, it is more modest as the NNT is higher (between 149-199) for this lower-risk group. Therefore, we thought that this should be a decision between the patient and their provider, and the discussion should include any other risk factors the person may have. If there are other risk factors, whether they are HIV-related or non-HIV–related—like a family history of premature CVD or coronary calcifications on a chest CT scan—these added CVD risks should be taken into account if people have <5% risk.

What are other HIV-related risk factors for CVD? We know that older people with HIV have lived with the increased inflammation for decades and that people with low current and nadir CD4 cell counts have an increased risk of CVD.15

If a person living with HIV has high LDL (>190 mg/dL) or diabetes, we recommend following standard CV guidelines like those of the American College of Cardiology or American Heart Association.

Case Optimization: 2-Yr Visit

To optimize care for our female patient, lifestyle interventions, referral to a nutritionist, and starting on atorvastatin were discussed. Together we decided that she would focus on the nutrition and lifestyle interventions and not yet start on a GLP-1 RA like semaglutide.

Take-home Points

What are the take-home points? In term of INSTIs, they are still the first-line regimen recommended for most people. There are conflicting data about their association with CV risk and so more longer-term studies are needed. However, it does not mean that we should give up on them as a first line treatment. I think the data we have show that they are still the safest first-line regimen that is currently available.

Weight gain is common regardless of ART and regardless of INSTI use, so you should talk to patients about weight gain, especially if they are women, and especially if they are Black women. Weight gain is not just cosmetic: it is something to be concerned about as the fat seems to deposit deep in the visceral depots and in other organs like the liver, and it is associated with increased risk of diabetes and MASLD.

Among the GLP-1 RAs, semaglutide is the one that now has some data in HIV in 2 separate studies. GLP-1 RAs may decrease weight, visceral fat and liver fat. However, we require more data in our HIV population because of the concern for loss of muscle fat or muscle mass, and potentially exacerbating lipoatrophy.

Statins for CV risk should be given if people have an ASCVD risk score of 5% or more. However, since the ASCVD risk calculation probably underestimates the risk in people living with HIV, I would recommend considering statin therapy for those with lower risk scores as well.