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Atorvastatin for 1 year trims coronary artery
plaque volume and number in placebo trial
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CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
One year of atorvastatin significantly lowered coronary artery plaque volume and reduced the number of high-risk plaques in a placebo-controlled trial of HIV-positive people with subclinical atherosclerosis [1]. Janet Lo and colleagues from Massachusetts General Hospital published their findings shortly before CROI 2015 [2].
Because cardiovascular disease poses a threat to HIV-positive people now living longer on antiretroviral therapy, research has begun to explore ways to cut heart disease risk in people with HIV. Current US Health Resources and Services Administration guidelines recommend statins as first-line therapy for HIV-positive people with (1) high low-density lipoprotein (LDL) cholesterol alone or (2) high LDL cholesterol plus triglycerides between 200 and 500 mg/dL [3]. General population guidelines recommend statins for people over 20 years old with LDL cholesterol at or above 190 mg/dL. But some studies indicate that statins pose a risk of diabetes in people with HIV [4].
Research by the Massachusetts General team and others found higher rates of asymptomatic atherosclerosis and potentially dangerous noncalcified plaque in HIV-positive than HIV-negative people [5-7]. To see whether standard statin therapy affects plaque in people with HIV, Lo and colleagues conducted a double-blind placebo-controlled trial [1,2].
The investigators recruited 40 HIV-positive men and women with no history of cardiovascular disease, with one or more plaques on coronary CT angiography (CCTA), but without left main artery stenosis or more than 70% stenosis of any major vessel. All participants were 18 to 60 years old, taking a stable antiretroviral regimen for at least 6 months, and had LDL cholesterol levels between 70 and 130 mg/dL. The researchers randomized them to 40 mg of atorvastatin daily or to placebo, and the dose could be cut if lab abnormalities or myalgia developed.
Twenty of 21 people assigned to placebo and 17 of 19 assigned to atorvastatin (20 mg escalated to 40 mg) completed 12 months of follow-up. Most study participants (80%) were men and age averaged about 51 years. Two thirds (68%) were white, 16% black, and 5% Hispanic. Average baseline CD4 counts exceeded 500, and median viral load stood below 48 copies.
After 12 months FDG-PET scans of the aorta showed no difference in arterial inflammation between the atorvastatin group and the placebo group, but the investigators had technically adequate results for only 21 of 37 people.
In all 37 people who completed the trial, four other measures indicated significant improvement in coronary artery plaque volume or number with atorvastatin versus placebo:
-- Change in total plaque volume: -4.7% atorvastatin vs +18.2% placebo (P = 0.01)
-- Change in noncalcified plaque volume: -19.4% atorvastatin vs +20.4% placebo (P = 0.009)
-- Average number of low-attenuation plaques: -0.2 atorvastatin vs +0.4 placebo (P = 0.03)
-- Average number of positively remodeled plaques: -0.2 atorvastatin vs +0.4 placebo (P = 0.04)
Noncalcified plaques, low-attenuation plaques, and positively remodeled plaques are judged high-risk plaques. Eleven of 17 people (65%) randomized to atorvastatin and 4 of 20 (20%) randomized to placebo had regression in total plaque volume (P = 0.0085).
Direct LDL cholesterol improved significantly with atorvastatin (-1.00 mmol/L, 95% confidence interval [CI] -1.38 to 0.61) compared with placebo (0.30 mmol/L, 95% CI 0.04 to 0.55, P < 0.0001). Lipoprotein-associated phospholipase A2, a marker of vascular inflammation, fell significantly more in the atorvastatin group (-52.2 ng/mL, 95% CI -70.4 to -34.0) than in the placebo group (-13.3 ng/mL, 95% CI -32.8 to +6.2) (P = 0.005).
No one in either study arm had an adverse event leading them to stop a study drug. One person in each arm had an adverse event leading to dose reduction. Two people taking atorvastatin and 1 taking placebo had a serious adverse event. Six people taking atorvastatin and 5 taking placebo had muscle aches or cramps.
The Massachusetts General researchers suggested their findings are "relevant to the many patients with HIV and subclinical atherosclerotic disease--more than half of the asymptomatic patients screened for our study" [2]. They proposed that "evidence for increased atherosclerotic disease progression in HIV-infected patients suggests the need for more aggressive treatment with statins as in other high-risk populations" [2].
Another placebo-controlled trial presented at this CROI session and reported separately by NATAP found that 96 weeks of rosuvastatin stopped progression of carotid artery intima-media thickness, a predictor of atherosclerosis, in people with LDL cholesterol below 130 mg/dL and well controlled HIV infection [8].
References
1. Lo J Lu M, Ihenachor E, et al. Statin therapy reduces coronary noncalcified plaque volume in HIV patients: a randomized controlled trial. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 136.
2. Lo J, Lu MT, Ihenachor EJ, et al. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2015;2:e52-e63.
3. US Department of Health and Human Services Health Resources and Services Administration. Guide for HIV/AIDS Clinical Care. April 2014.
4. Ahmed MH, Al-Atta A, Hamad MA. The safety and effectiveness of statins as treatment for HIV-dyslipidemia: the evidence so far and the future challenges. Expert Opin Pharmacother. 2012;13:1901-1909.
5. Lo J, Abbara S, Shturman L, et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS. 2010;24:243-253.
6. Post WS, Budoff M, Kingsley L, et al. Associations between HIV infection and subclinical coronary atherosclerosis Ann Intern Med. 2014;160:458-467.
7. Fitch KV, Srinivasa S, Abbara S, et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis. 2013;208:1737-1746.
8. Longenecker CT Jiang Y, Debanne SM, et al. Rosuvastatin arrests progression of carotid intima-media thickness in treated HIV. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 137.
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