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Long-term Antilipid Therapy Tied to
70% Lower Death Risk in VA Cohort
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17th European AIDS Conference, November 6-9, 2019, Basel
Mark Mascolini
Long-term lipid-lowering therapy with statins alone halved the death risk in a mostly male group of more than 23,000 US veterans [1]. Long-term use of nonstatin lipid-lowering agents cut the death risk by up to 70%.
Investigators from the VA North Texas Health Care System and collaborators from other centers noted that research links statin therapy to lower all-cause mortality [2] and decreased rates of non-AIDS conditions like non-AIDS cancer [3]. But the impact of other, often coadministered lipid-lowering agents on mortality in people with HIV has not been well studied. The VA team aimed to assess the potential impact of individual and combined antilipid therapy in people with HIV, including statins, antihypertensives, and aspirin.
The researchers used the VA Clinical Case Registry to identify all HIV-positive US veterans who achieved HIV control after starting antiretroviral therapy from 1996 through 2011. Using time-updated exposure categories for each drug class analyzed, they explored five endpoints: (1) death or first occurrence of (2) an acute coronary event, (3) an acute cerebrovascular event, (4) severe infection, or (5) cancer. They grouped cardiovascular preventive medication exposure into mutually exclusive time-updated categories: (1) long-term use (exclusive statin, nonstatin, or combination therapy for at least the past 11 months), (2) recent use (any use in the past year), (3) remote use (last use more than 1 year ago), and (4) never exposed.
The VA researchers tracked more than 23,000 people for a median of 5.2 years, splitting them into three groups by year of first antiretroviral use: 7434 people in 1996-2000, 7855 in 2001-2005, and 7987 in 2006-2011. Median ages of those three groups were 50, 53, and 56, proportions of blacks and whites 38% and 34%, 48% and 39%, and 53% and 37%, and proportions of smokers 52%, 59%, and 57%. Only 2.5% of participants were women.
A sizeable minority of participants, 42%, had taken lipid-lowering therapy, including 36% on statins, 21% on nonstatin antilipid drugs (fibrates, fish oil, ezetimibe, and niacin), and 15% who had taken both statins and nonstatin antilipids. People who started these agents continued taking them for 54% of their follow-up time. While participants with long-term lipid-lowering therapy took antihypertensives for 59% of follow-up time, they took aspirin for 19% of that time. Only 38% took no other cardiovascular preventive medication.
An inverse probability weighting model controlling for all exposure levels of lipid-lowering therapy, antihypertensives, and aspirin determined that long-term use of statins alone halved the risk of death (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37 to 0.70, P = 0.0001). Combination long-term antilipid therapy cut the death risk by almost two-thirds (HR 0.37, 95% CI 0.24 to 0.56, P < 0.0001). And long-term use of only nonstatin antilipids sliced the death risk by 70% (HR 0.30, 95% CI 0.17 to 0.52, P < 0.0001). In contrast, this analysis linked long-term use of antihypertensive monotherapy alone to about a 40% higher death risk (HR 1.41, 95% CI 1.23 to 1.62, P < 0.0001), while long-term combination antihypertensive therapy was associated with a 30% higher death risk (HR 1.31, 95% CI 1.04 to 1.66, P = 0.04). Recent but not remote use of any lipid-lowering therapy was associated with a lower death risk.
The same analysis linked long-term statin-only therapy to a lower risk of severe infection (HR 0.57, 95% CI 0.46 to 0.72, P < 0.0001) and cancer (HR 0.63, 95% CI 0.47 to 0.85, P = 0.006), but not to a lower risk of coronary or cerebrovascular events. Long-term combination antilipid therapy was linked to a lower risk of a cerebrovascular event (HR 0.13, 95% CI 0.06 to 0.028, P < 0.0001) and severe infection (HR 0.62, 95% CI 0.45 to 0.87, P = 0.01).
The analysis tied long-term nonstatin-only antilipid therapy to a lower risk of an acute coronary event (HR 0.29, 95% CI 0.09 to 0.89¸ P = 0.05) or a cerebrovascular event (HR 0.21, 95% CI 0.06 to 0.77, P = 0.04).
The VA investigators suggested four important interpretations of their findings: (1) results apply to the modern combination antiretroviral therapy era, (2) decreased mortality associated with long-term statin use reflects "pleiotropic immunologic effects," not reduced cardiovascular events, (3) long-term nonstatin antilipid therapy lowers both cardiovascular disease risk and mortality, and (4) "the relationship between lipid-lowering therapy use and reduced mortality in HIV is likely causal in nature."
References
1. Drechsler H, Ayers C, Bedimo R. Long-term lipid-lowering-therapy in HIV is clinically effective. 17th European AIDS Conference, November 6-9, 2019, Basel. Abstract PE9/89.
2. Moore RD, Bartlett JG, Gallant JE. Association between use of HMG CoA reductase inhibitors and mortality in HIV-infected patients. PLoS One. 2011;6:e21843. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0021843
3. Overton ET, Kitch D, Benson CA, et al. Effect of statin therapy in reducing the risk of serious non-AIDS-defining events and nonaccidental death. Clin Infect Dis. 2013;56:1471-1479.
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