Compared with placebo in people with HIV infection, pitavastatin decreased the risk of major adverse cardiovascular events over a median follow-up of 5.1 years, researchers report. “The effect size in men and women appeared to be similar,” write the authors. “The high risk of HIV-associated cardiovascular disease among women is an important concern in the field, and these data provide reassurance about relative statin effectiveness in this understudied population.”
The phase 3 REPRIEVE trial included 7,769 participants with HIV infection with a low-to-moderate risk of cardiovascular disease who were receiving antiretroviral therapy. Randomized to daily pitavastatin calcium 4 mg or placebo, participants were assessed for the primary outcome of the occurrence of a major adverse cardiovascular event (a composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause).
“The median age of the participants was 50 years (interquartile range, 45 to 55); the median CD4 count was 621 cells per cubic millimeter (interquartile range, 448 to 827), and the HIV RNA value was below quantification in 5,250 of 5,997 participants (87.5%) with available data,” the authors write. “The trial was stopped early for efficacy after a median follow-up of 5.1 years (interquartile range, 4.3 to 5.9). The incidence of a major adverse cardiovascular event was 4.81 per 1,000 person-years in the pitavastatin group and 7.32 per 1,000 person-years in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.48 to 0.90; P = 0.002). Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 participants (5.3%) and in 155 (4.0%), respectively.”
Editorial: “This trial underscores the importance of cardiovascular disease prevention measures,” writes an editorialist. “Although pitavastatin targets one and perhaps two important risk factors for atherosclerotic cardiovascular disease (i.e., LDL cholesterol and systemic inflammation), other risk factors merit attention for this preventive approach to be transformative. Hypertension and diabetes are often routinely addressed in clinical care, although behavioral risk factors such as cigarette smoking, unhealthy alcohol consumption, drug use, obesity, and mental health conditions are often underassessed, underaddressed, or both, in part because these risk factors can be challenging to modify. Moreover, alcohol consumption at lower doses can result in a higher risk of physiological injury among persons with HIV infection. Thus, targeting of these less traditional risk factors in this population could result in beneficial effects, either directly on the cardiovascular system or indirectly by reducing systemic inflammation. As part of this overall effort, this trial represents a necessary first step toward a comprehensive preventive approach to reducing the risk of cardiovascular disease among persons with HIV infection.”
In an Intent to Treat interview in the Journal‘s Perspective column, the lead REPRIEVE investigator comments on the role of cardiovascular disease in a mortality gap seen in people with HIV: “I think this [study] is a game changer, because we’ve got the virus pretty much under control with the use of effective antiretroviral therapy, but the problem that’s emerged is people living with HIV are now living with a chronic disease. It happens to be a chronic inflammatory disease. So they’re living with this chronic inflammatory disease, yet there’s been no focus on that. The only focus has been to get the virus in check — which is great, but it’s not enough. It’s critical, but not sufficient.”