Incidence, risk factors, and cardiovascular impact of hypertension in people with HIV: a secondary analysis of the REPRIEVE trial.

Abstract

People living with HIV have an increased risk of cardiovascular disease, but data on the development and consequences of hypertension remain limited. Using data from REPRIEVE, a global randomised trial of pitavastatin for primary cardiovascular prevention among people with HIV, we evaluated whether pitavastatin reduces the incidence of hypertension among participants without hypertension at baseline and whether incident hypertension is associated with subsequent major adverse cardiovascular events (MACE). We conducted a prespecified secondary analysis of participants without evidence of hypertension at REPRIEVE entry (baseline). REPRIEVE (NCT02344290) was a global, randomised, double-blind, placebo-controlled trial that enrolled adults with HIV aged 40-75 years at low-to-moderate atherosclerotic cardiovascular risk, receiving stable antiretroviral therapy. The primary outcome in this secondary analysis was incident hypertension based on clinical diagnosis according to standard criteria. Included participants were those without hypertension at baseline; excluded were those with documented hypertension, antihypertensive treatment use, systolic blood pressure of 140 mm Hg or higher, or diastolic blood pressure of 90 mm Hg or higher. The association between incident hypertension and a secondary outcome of MACE was evaluated in a time-updated analysis. Analyses used both Cox and Fine-Gray proportional hazards models and Poisson regression. Of 7769 participants enrolled in REPRIEVE, 4989 (64%) without hypertension at baseline were included (2496 assigned to pitavastatin and 2493 to placebo) in this secondary analysis. The median age was 49 years (IQR 45-54); 1464 (29%) were women and 3525 (71%) men; and the median systolic and diastolic blood pressures at baseline were 102 mm Hg and 76 mm Hg, respectively. Over a median follow-up of 5·0 years (IQR 4·4-5·8), 668 (13%) participants developed hypertension. Participants randomly assigned to pitavastatin showed a modestly lower incidence of hypertension (24·7 per 1000 person-years vs 29·6 per 1000 person-years), corresponding to a 17% relative risk reduction (cause-specific hazard ratio [HR] 0·83, 95% CI 0·71-0·97; p=0·017). Risk factors of incident hypertension included old age, high BMI, metabolic syndrome, reduced estimated glomerular filtration rate (eGFR), and Black race in high-income regions. Among participants with incident hypertension, 581 (87%) initiated antihypertensive therapy. Of 213 who initiated antihypertensive therapy after diagnosis of hypertension, 159 (74·6%) were controlled 4 years after diagnosis. Incident hypertension was associated with a higher risk of MACE during follow-up (subdistribution HR 2·16, 95% CI 1·32-3·52) in modelling adjusted for baseline cardiovascular risk score. These findings suggest additional cardiovascular benefits of pitavastatin on hypertension among people with HIV targeted for primary cardiovascular prevention. National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, ViiV Healthcare, Instituto de Salud Carlos III, and the European Regional Development Fund.