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Dyslipidemia and Elevated CVD Risk
Choosing Statins for Patients With Dyslipidemia and Elevated CVD Risk

Released: June 01, 2017

Expiration: May 31, 2018

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In this HIV cases series, we highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. In the case that follows, an older man with long-time HIV infection and a history of hypertension is experiencing dyslipidemia. Follow discussion of the ensuing decision pathways to determine if a statin is needed, and if so, which one would be most appropriate.

Case Details
A 60-year-old man living with HIV infection for more than 20 years relocates from another state. He is currently receiving darunavir (DRV)/cobicistat (COBI) plus tenofovir alafenamide (TAF)/emtricitabine (FTC) but has an extensive previous ART history, which has prompted accumulation of drug resistance mutations to thymidine analogues, older PIs, and all agents in the nonnucleoside class. Furthermore, he was treated with raltegravir a few years ago but stopped soon after initiation because of fatigue and headache that resolved with discontinuation. His HIV-1 RNA has been undetectable for many years, and his CD4+ cell count is approximately 700 cells/mm3. He has a history of hypertension treated effectively (138/80 mm Hg) with the diuretic chlorthalidone and is a former smoker, having quit 3 years ago. His body mass index is 28.

The patient knows from recent testing that his cholesterol is elevated, but he has held off on starting lipid-lowering medication in favor of trying to bring the numbers down with diet and exercise. Unfortunately, his weight has increased 5 pounds in the last year. A lipid panel is drawn and confirms dyslipidemia with a total cholesterol of 260 mg/dL, an LDL of 169 mg/dL, an HDL of 40 mg/dL, and triglycerides of 225 mg/dL. He has read that people living with HIV infection are at higher risk for cardiovascular disease than those who are HIV negative and asks if he really needs to be on a statin.

Assessing Risk
Medical decision making relies on the consideration of the risks vs benefits of evidence-based interventions and then tempering this with provider and patient preferences. Much work has gone into developing approaches to quantify the risk of cardiovascular disease, the major cause of mortality in developed nations. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) issued guidelines on cardiovascular disease prevention that included a revised calculator to estimate risk of heart attack and stroke, largely replacing the long-standing Framingham algorithm. Plugging our patient’s data into the ACC/AHA’s ASCVD calculator, we see that his 10-year risk of cardiovascular disease is approximately 17%. The ACC/AHA guidelines state that adults 40-75 years of age with an LDL cholesterol level of 70-189 mg/dL with no diabetes and an estimated 10-year ASCVD risk of ≥ 7.5% should be treated with a moderate-intensity or high-intensity statin. So, clearly this man should be advised to start statin therapy, especially because some data suggest that cardiovascular risk assessments developed in the general population underestimate risk in those with HIV infection.

Certainly, the patient’s aspirational plans for eating well and exercising more should also be encouraged. The Mediterranean diet is practical and relatively easy to follow and has been found to reduce weight, atherogenic lipid levels, blood sugar, and inflammatory markers. Brief, high intensity exercise can be attractive to some patients who have been unable to commit to the longer periods of exercise.

Not All Statins Are Created Equal
Just as some PIs are more potent than others, certain statins are considered higher intensity than others, especially when used at larger doses. The designation of statin intensity is based on the anticipated LDL cholesterol lowering effects, which are derived from clinical trial data. Moderate-intensity statins are expected to reduce LDL by 30% to 50% whereas the high-intensity statins should drop LDL by more than 50%. The ACC/AHA guidelines match statin choice and dose with estimated risk such that higher-intensity statin therapy is recommended for those at greatest risk of cardiovascular disease.

Factoring in HIV
For this patient, the guidelines recommend at least a moderate-intensity statin. If we feel that his HIV infection and cardiovascular history raise his risk beyond that estimated by the calculator, a more aggressive approach to LDL lowering would be justified.

A complicating factor is this patient’s ART. He is being treated with COBI, a pharmacologic booster that is needed to raise the level of DRV but that can inhibit the metabolism of other medications, such as statins, that rely on the cytochrome P450 enzymes within the liver. The effect of pharmacologic boosters such as COBI and ritonavir (RTV) can vary by statin. Drug–drug interaction checkers are useful tools in preventing these coadministration complications.

For instance, simvastatin and lovastatin exposure increases are expected with coadministration of a pharmacologic booster and may trigger rhabdomyolysis. Because of this potential toxicity, these statins should be avoided in our patient. Atorvastatin or rosuvastatin would be suggested for this patient, although dose adjustments may still be needed for patients receiving COBI or RTV. Unfortunately, there may not be an easy path to changing his ART away from a pharmacologic booster given his accumulated ART resistance and well-documented intolerance to an INSTI.

Table. Statin Therapy for Patients With HIV

Therefore, for this man with significant cardiovascular risk and use of a pharmacologic booster, high-intensity atorvastatin (covered by his insurance) would be reasonable to try while watching carefully for any adverse events (eg, muscle aches, fatigue). High-intensity rosuvastatin would also be an option. A dose that would start him at the lower end of high-intensity statin therapy would be appropriate.

Your Thoughts
HIV care providers are experts in the strategic use of ARVs, wielding them expertly to beat back the threat of HIV, but mastering use of primary care medications such as antihypertensives, diabetes agents, and lipid-lowering therapies is an ongoing process. As our patients live longer and accumulate the conditions that accompany aging, it is becoming clear that preventing and treating comorbid disease is second only to viral suppression in impact on extending and enhancing the lives of people living with HIV infection. How would you manage dyslipidemia in this patient? Would you take a different lipid-lowering approach? Would you try a switch in his ART, such as a trial of dolutegravir instead of his PI? I invite you to join our conversation in the comments box below.

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How would you manage dyslipidemia in the case patient, who has a history of hypertension and is currently receiving ART that includes COBI?
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