Pitavastatin Lowers Cholesterol More Effectively Than Pravastatin in HIV

The percentage change in fasting low-density lipoproteins at 12 weeks was higher in the pitavastatin group than in the pravastatin group.
The percentage change in fasting low-density lipoproteins at 12 weeks was higher in the pitavastatin group than in the pravastatin group.

Pitavastatin had greater low-density lipoprotein (LDL)-lowering effects than pravastatin without unfavorable effects on glucose metabolism or rates of virological failure in patients with HIV and dyslipidemia. Results of the INTREPID (HIV-Infected Patients and Treatment With Pitavastatin vs Pravastatin for Dyslipidemia) study were published in the Lancet HIV.1

"Nowadays, the treatment of HIV is very effective, and patients who take antiviral medications often do well and lead a normal life. What's happened with HIV is that the other factors that affect a person's health have become more important," Douglas J. Ward, MD, from Dupont Circle Physicians Group and clinical associate professor of medicine at George Washington University Medical School in Washington, DC, told Infectious Disease Advisor. "There is a high incidence of elevated cholesterol in the HIV population. In addition, the HIV population is at greater risk for heart disease due to a higher incidence of smoking and HIV itself, so it's really important to control cholesterol in this population."

According to Dr Ward, pravastatin is commonly the statin of choice for patients with HIV with hyperlipidemia. Pravastatin, unlike most other statins, does not rely on the cytochrome P450 (CYP) enzyme system for metabolism, and is therefore less likely to interact with HIV medications, such as protease inhibitors, that depend on CYP metabolism. Pravastatin, however, is "one of the weakest of the statins, and may still have some potential interactions with the protease inhibitors or other HIV medications."

Pitavastatin is minimally metabolized by the CYP system and does not have clinically meaningful interactions with protease inhibitor therapy.1 A previous phase 3 study showed that compared with pravastatin, pitavastatin significantly decreased LDL in elderly patients with dyslipidemia.2

In the phase 4 INTREPID study, researchers led by Dr Ward and Judith A. Aberg, MD, from the Icahn School of Medicine at Mount Sinai in New York, compared the safety and efficacy of pitavastatin with that of pravastatin in adult patients (aged 18-70 years) with HIV and dyslipidemia.1

A total of 252 patients with controlled HIV (defined as CD4 counts >200 cells/μL and HIV-1 RNA <200 copies/mL) were randomly assigned in a 1:1 ratio to receive pravastatin or pitavastatin.1

The percentage change in fasting LDL at 12 weeks, the primary endpoint, was higher in the pitavastatin group than in the pravastatin group (31.1% vs 20.9% LDL reduction, respectively; P <.0001). Pitavastatin also reduced non-HDL cholesterol and apolipoprotein B to a greater extent than pravastatin.1

Rates of virological failure at 1 year were similar in both groups (3% for pitavastatin vs 5% for pravastatin).

Patients with HIV have an increased risk for impaired glucose metabolism, and statins may promote insulin resistance. However, both treatments had no significant effect on fasting blood glucose, fasting plasma insulin, or HbA1c.1

Rates of treatment-emergent adverse events were similar in the pravastatin and pitavastatin groups (70% vs 68%). Diarrhea and upper respiratory tract infection were the most common adverse events in the pitavastatin and pravastatin groups, respectively. Serious adverse events occurred in 6% of pitavastatin patients compared with 2% of pravastatin patients.1

"The INTREPID trial showed that pitavastatin is well-tolerated and more effective at lowering cholesterol, particularly LDL cholesterol, compared to the traditional go-to statin, pravastatin," Dr Ward concluded.

"However, this trial does not answer the question of whether statins reduce the risk of heart disease in this population," he noted. "The ongoing REPRIEVE trial, which is looking at using pitavastatin to reduce heart disease in HIV patients, hopefully will give us some information on that question."

This study was funded by Eli Lilly and Kowa Pharmaceuticals America. Dr Ward reports financial relationships with ViiV Healthcare, Gilead Sciences, Bristol-Myers Squibb, and Janssen.

References

  1. Aberg JA, Sponseller CA, Ward DJ, Kryzhanovski VA, Campbell SE, Thompson MA. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial [published online April 13, 2017]. Lancet HIV. doi: 10.1016/S2352-3018(17)30075-9
  2. Stender S, Budinski D, Gosho M, Hounslow N. Pitavastatin shows greater lipid-lowering efficacy over 12 weeks than pravastatin in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia. Eur J Prev Cardiol. 2013;20:40-53. doi: 10.1177/2047487312451251
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