Clinical question: Does pitavastatin decrease major adverse cardiovascular events (MACEs) in patients infected by the human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART) and who are at low to moderate risk of cardiovascular disease?
Background: HIV is a common global infection and patients with HIV infection are at significantly increased risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and stroke, compared to non-HIV patients. Now that ART is widely available and used, the cause of death for patients infected with HIV is frequently related to cardiovascular disease. ASCVD risk scores traditionally used for initiating statins do not incorporate the increased cardiovascular risk associated with HIV infection. It is postulated that the excess risk remains even when traditional risk factors are addressed and may be related to underlying immune activation and inflammation. This study highlights that pitavastatin use can decrease MACEs in patients with HIV who are on antiretroviral therapy.
Study design: Multicenter, randomized, placebo-controlled trial (REPRIEVE)
Setting: 7,769 people aged 40 to 75 years with low to moderate CV risk with HIV on ART were recruited from 145 sites in 12 different countries
Synopsis: This trial was a multinational, randomized, placebo-controlled, efficacy study where patients were randomized to receive pitavastatin or placebo. The participants were between the ages of 40 and 75 years and on ART therapy, with a low-to-moderate risk of ASCVD. Patients with known ASCVD were excluded from the trial. The median calculated 10-year ASCVD risk score was 4.5%. Pitavastatin was used because of its low interaction risk with ART. The primary outcome was the occurrence of a MACE. Data showed that MACEs were significantly lower in the pitavastatin group, with the incidence being 4.81 per 1,000 person-years versus 7.32 per 1,000 person-years in the placebo group (HR, 0.65; P=.002). The trial was stopped early due to the efficacy of pitavastatin at lowering the incidence of MACE versus placebo (35% risk reduction) over the median follow-up of 5.1 years. The authors report the five-year NNT is 106.
Although non-fatal adverse events were similar, the pitavastatin group had slightly higher rates of diabetes mellitus and myopathy or myalgia of grade 3 or higher. The use of only pitavastatin for treatment is a limitation of this study, making the results specific to this drug.
Bottom line: Pitavastatin can reduce the risk of major cardiovascular events in people with HIV infection on ART, especially those in the moderate cardiovascular risk group. It is unclear if using a different statin that does not interact with the patient’s ART would provide the same benefit.
Citation: Grinspoon SK, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389(8):687-99.
Dr. McCutcheon
Dr. McCutcheon is a hospitalist at Atrium Health in Charlotte, N.C.