Abstract
BackgroundRecent studies have suggested that statins possess diverse immune modulatory and anti-inflammatory properties. As statins might attenuate inflammation, statin therapy has been hypothesized to reduce mortality in HIV-infected individuals. We therefore used a Danish nationwide cohort of HIV-infected individuals to estimate the impact of statin use on mortality before and after a diagnosis of cardiovascular disease, chronic kidney disease or diabetes.MethodsWe identified all Danish HIV-infected individuals (1,738) who initiated HAART after 1 January 1998, and achieved virological suppression within 180 days. Date of first redemption of a prescription of statin was obtained from the Danish National Prescription Registry. We used Poisson regression analysis to assess adjusted mortality rate ratios (aMRR). First, time was censored at date of virological failure (VL >500 copies/ml). Second, time was not censored at virological failure. All analyses were adjusted for potential confounders.ResultsIn the analyses confined to observation time without virological failure (+ censoring) statin therapy was associated with a non-statistically significant reduced rate of death (aMRR 0.75; 95% CI: 0.33–1.68). No difference was observed in the analysis with no censoring (aMRR 1.17; 95% CI: 0.66–2.07). Use of statin seemed to reduce mortality in individuals after a diagnosis of comorbidity {(+ censoring: aMRR: 0.34; 95% CI: 0.11–1.04), (−censoring: aMRR: 0.64; 95% CI: 0.32–1.29)}. No difference in rate of death could be detected before first date of diagnosis of comorbidity {(+ censoring: aMRR: 1.12; 95% CI: 0.34–3.62), (−censoring: aMRR: 0.90; 95% CI: 0.28–2.88)}.ConclusionStatin therapy might reduce all-cause mortality in HIV-infected individuals, but the impact on individuals with no comorbidity seems small or absent. An unambiguous proof of a causal relation can only be obtained in a randomized controlled trial, but the sample size predicted may be prohibitive for its conduct.
Highlights
HMG CoA Reductase Inhibitors are cholesterollowering drugs used extensively in the primary and secondary prevention of cardiovascular disease [1]
The study cohort consisted of 1,738 HIV-infected individuals who initiated highly active antiretroviral therapy (HAART) on 1 January 1998 or after this date and within 180 days of that had a viral loads (VL),50 copies/ml
In the analysis confined to observation time without virological failure we found an adjusted mortality rate ratios (aMRR) of 0.75 for the time after versus the time before or with no initiation of a statin (Table 3)
Summary
HMG CoA Reductase Inhibitors (statins) are cholesterollowering drugs used extensively in the primary and secondary prevention of cardiovascular disease [1]. Recent studies though have suggested that statins possess cholesterol-independent or pleitropic effects including diverse immune modulatory and antiinflammatory properties [2,3]. A wide range of beneficial effects have been hypothesized. It is well established by several large clinical trials [4,5,6,7,8,9] that statin therapy can reduce the risk of coronary and cerebrovascular events, and decrease mortality due to coronary artery disease. During the last years a large number of cohort studies have investigated the impact of statin therapy on mortality for a wide range of other medical conditions. Recent studies have suggested that statins possess diverse immune modulatory and anti-inflammatory properties. We used a Danish nationwide cohort of HIV-infected individuals to estimate the impact of statin use on mortality before and after a diagnosis of cardiovascular disease, chronic kidney disease or diabetes
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