0
Original Research: Diffuse Lung Disease |

Retrospective Review of Combined Sirolimus and Simvastatin Therapy in LymphangioleiomyomatosisStatins in Lymphangioleiomyomatosis

Angelo M. Taveira-DaSilva, MD, PhD; Amanda M. Jones, CRNP; Patricia A. Julien-Williams, CRNP; Mario Stylianou, PhD; Joel Moss, MD, PhD, FCCP
Author and Funding Information

From the Cardiovascular and Pulmonary Branch (Drs Taveira-DaSilva and Moss and Mss Jones and Julien-Williams) and Office of Biostatistics Research (Dr Stylianou), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

CORRESPONDENCE TO: Angelo M. Taveira-DaSilva, MD, PhD, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590; e-mail: dasilvaa@nhlbi.nih.gov


FUNDING/SUPPORT: This study was supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(1):180-187. doi:10.1378/chest.14-0758
Text Size: A A A
Published online

BACKGROUND:  Combined simvastatin and sirolimus therapy reduces tuberous sclerosis complex 2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit patients with LAM.

METHODS:  To determine whether simvastatin changed the prevalence of adverse events or altered the therapeutic effects of sirolimus, we recorded adverse events and changes in lung function in patients with LAM treated with simvastatin plus sirolimus (n = 14), sirolimus alone (n = 44), or simvastatin alone (n = 20).

RESULTS:  Sirolimus-related adverse events in the simvastatin plus sirolimus and sirolimus-only groups were 64% and 66% for stomatitis, 50% and 52% for diarrhea, 50% and 45% for peripheral edema, 36% and 61% for acne, 36% and 30% for hypertension, 29% and 27% for proteinuria, 29% and 27% for leukopenia, and 21% and 27% for hypercholesterolemia. The frequency of simvastatin-related adverse events in the simvastatin-only and simvastatin plus sirolimus groups were 60% and 50% for arthralgias and 35% and 36% for myopathy. Before simvastatin plus sirolimus therapy, FEV1 and diffusing capacity of the lung for carbon monoxide (Dlco) yearly rates of change were, respectively, −1.4 ± 0.2 and −1.8 ± 0.2% predicted. After simvastatin plus sirolimus therapy, these rates changed to +1.2 ± 0.5 (P = .635) and +0.3 ± 0.4% predicted (P = .412), respectively. In 44 patients treated with sirolimus alone, FEV1 and Dlco rates of change were −1.7 ± 0.1 and −2.2 ± 0.1% predicted before treatment and +1.7 ± 0.3 and +0.7 ± 0.3% predicted after treatment (P < .001).

CONCLUSIONS:  Therapy with sirolimus and simvastatin does not increase the prevalence of drug adverse events or alter the therapeutic effects of sirolimus.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543