No evidence of pitavastatin effect on muscle area or density among people with HIV

Abstract

Background: Skeletal muscle area and muscle density are key determinants of physical function and typically decline with increasing age. Statins have well known musculoskeletal effects but whether statins impact muscle area or muscle density is not well established, especially in the setting of randomized treatment.

Methods: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus muscle area and muscle density were assessed among Mechanistic Substudy participants with CT at baseline and month 24.

Results: Of 804 substudy participants, 510 remained on study treatment and had imaging at baseline and month 24. Median age was 51 years; 17% were natal female, 35% Black, and 27% Hispanic. There were no apparent changes in muscle measures from baseline to month 24 within the treatment groups. The estimated treatment group differences in baseline-adjusted month 24 outcomes were minimal [within 0.5 cm 2 /m for height-adjusted MA with 95% confidence interval (95% CI) bounds within <1 cm 2 /m, and within 1 Hounsfield units (HU) for MD with 95% CI bounds within <3 HU; all P > 0.2]. Findings were generally consistent in subgroup analyses.

Conclusion: Pitavastatin was associated with no apparent change in muscle measures over 24 months, and with no evidence of detrimental effect among PWH.

Keywords: HIV; muscle area; muscle density; myosteatosis; sarcopenia; statin.

Figure 1:. Thoracic paraspinal, pectoralis and infraspinatus muscles on non-contrast CT images.

The paraspinal muscles in the lower thorax (in green, on the left), pectoralis (anterior thoracic wall; in yellow; on the right) and infraspinatus (shoulder; in red; on the right) muscles were measured.

Figure 1:. Thoracic paraspinal, pectoralis and infraspinatus muscles on non-contrast CT images.

The paraspinal muscles in the lower thorax (in green, on the left), pectoralis (anterior thoracic wall; in yellow; on the right) and infraspinatus (shoulder; in red; on the right) muscles were measured.

Figure 2.. Estimated Pitavastatin Effect on Muscle Area in Subgroups by Baseline Characteristics in the Per-Protocol Population

(a) Paraspinal Muscle Area, Height-Adjusted (b) Pectoralis Muscle Area, Height-Adjusted (c) Infraspinatus Muscle Area, Height-Adjusted Treatment group differences in in baseline-adjusted muscle area measures at month 24 (pitavastatin minus placebo) are shown on the x axes. Greater muscle area is considered favorable. Positive treatment group differences favor pitavastatin, negative placebo. Treatment effect estimates are from linear regression models with muscle measure at month 24 as outcome, adjusted for baseline and main subgroup effect, in the per-protocol population. Modification of treatment effect was evaluated via treatment and subgroup variable interaction. Type 3 p-values are presented. Biomarkers were categorized based on the observed tertiles. For reference, the overall treatment effect estimate and 95% CI is shown on top (in orange).

Figure 2.. Estimated Pitavastatin Effect on Muscle Area in Subgroups by Baseline Characteristics in the Per-Protocol Population

(a) Paraspinal Muscle Area, Height-Adjusted (b) Pectoralis Muscle Area, Height-Adjusted (c) Infraspinatus Muscle Area, Height-Adjusted Treatment group differences in in baseline-adjusted muscle area measures at month 24 (pitavastatin minus placebo) are shown on the x axes. Greater muscle area is considered favorable. Positive treatment group differences favor pitavastatin, negative placebo. Treatment effect estimates are from linear regression models with muscle measure at month 24 as outcome, adjusted for baseline and main subgroup effect, in the per-protocol population. Modification of treatment effect was evaluated via treatment and subgroup variable interaction. Type 3 p-values are presented. Biomarkers were categorized based on the observed tertiles. For reference, the overall treatment effect estimate and 95% CI is shown on top (in orange).

Figure 2.. Estimated Pitavastatin Effect on Muscle Area in Subgroups by Baseline Characteristics in the Per-Protocol Population

(a) Paraspinal Muscle Area, Height-Adjusted (b) Pectoralis Muscle Area, Height-Adjusted (c) Infraspinatus Muscle Area, Height-Adjusted Treatment group differences in in baseline-adjusted muscle area measures at month 24 (pitavastatin minus placebo) are shown on the x axes. Greater muscle area is considered favorable. Positive treatment group differences favor pitavastatin, negative placebo. Treatment effect estimates are from linear regression models with muscle measure at month 24 as outcome, adjusted for baseline and main subgroup effect, in the per-protocol population. Modification of treatment effect was evaluated via treatment and subgroup variable interaction. Type 3 p-values are presented. Biomarkers were categorized based on the observed tertiles. For reference, the overall treatment effect estimate and 95% CI is shown on top (in orange).