Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

Abstract

BackgroundThe effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals.MethodsPatients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated.ResultsAmong 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights.ConclusionThe impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population.

Statin use and all-cause mortality in people living with HIV: a systematic review and meta-analysis

“… Rasmussen et al, [ 42 ] 2015 1998–2009 Cohort Denmark Danish HIV Cohort Study (DHCS) Primary prevention Total cholesterol > 5 mmol/L: 28.3% 73.1 39.3 (33.0–46.3) 1738 Not reported [10%] Age intervals (time-updated), gender, race, HIV-transmission group, hepatitis C status, calendar year of HAART initiation, AIDS defining illnesses prior to HAART, ART use before initiating HAART, CD4 cell count, viral load and cholesterol at HAART initiation. Krask et al, [ 38 ] 2015 2000–2015 Cohort USA Nutrition For Healthy Living (NFHL) Primary prevention Framingham score: 6.5, hypertensive: 35%, diabetic: 7%, smokers: 47%, metabolic syndrome: 23% 68 44.3 (7.7) 438 Not reported [15%] Race, HBV, HCV, LDL, CD4 cell count, age, smoking, statin duration Lang et al, [ 39 ] 2015 2000–2009 Cohort France French Hospital Database on HIV (FHDH-ANRS CO4) Primary prevention Current smokers: 42.1%, hypertensive 13.7%, diabetics: 10.1% 88.9 50.5 (10) 1776 Not reported [8%] Stepwise multivariable model using age, gender, HIV transmission group, current CD4 and CD8 T cell counts, CD4 T cell nadir, CD4/CD8 T cell ratio, CD4 T cell nadir/CD8 T cell ratio, plasma HIV-1 RNA level, AIDS status, the haemoglobin level, body mass index (BMI), smoking status, hypertension or use of antihypertensive treatment, diabetes or use of antidiabetic treatment, anti-HCV antibodies and HBs antigen status, non-AIDS malignancy (CIM-10 definition), liver failure, chronic kidney disease, cirrhosis, and pulmonary embolism. *Conference abstracts …”

“…The bias in selection of participants was moderate in four studies [ 36 , 38 , 41 , 42 ] and serious in three studies [ 37 , 39 , 40 ] For Knobel and colleagues study [ 37 ], the Framingham cardiovascular risk score above 20% was significantly higher among those on statin compared with those not on statins (21.4% versus 5.0%, RR = 2.95, 95% CI 2.22 to 3.92) and those on statin had significantly higher median total cholesterol (231 versus 178 mg/dL). Similarly, for Lang et al [ 39 ], the proportion of participants with hypertension (29.7% versus 12.4%) and type 2 diabetes mellitus (21.7% versus 9.1%) was significantly higher among those exposed to statins compared with those not on statins at baseline. For Moore and colleagues study [ 40 ], the proportion of participants on antihypertensive medications was significantly higher among those on statin compared with those not on statins (46.3% versus 25.6%).…”

Understanding mechanisms to promote successful aging in persons living with HIV

“…In retrospective studies, statins have been shown to reduce allcause mortality, decrease malignancy risk, and lower cirrhosis risk among HIV/HCV-co-infected patients (Lang et al, 2015;Moore et al, 2011;Overton et al, 2013;Chao et al, 2011;Galli et al, 2014;Oliver et al, 2016). It must be noted, however, that other studies have not shown a mortality benefit with statin use (Overton et al, 2013;Krsak et al, 2015;Rasmussen et al, 2013).…”

Serious Non-AIDS Events: Therapeutic Targets of Immune Activation and Chronic Inflammation in HIV Infection

“…In a small randomized, placebo controlled trial of 40 virologically suppressed individuals on ART, statin use was associated with reduced non-calcified plaque volume and high-risk coronary plaque [186]. In retrospective studies of individuals on ART, statin use has also been associated with reduction in mortality [187, 188]. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE, NCT02344290), involving 6500 individuals will shed further light on the effect of statin therapy on CVD and mortality in individuals on ART.…”