Download Statins in Preparation for Chemotherapy

Journal of the American College of Cardiology
© 2012 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Statins in
Preparation for Chemotherapy
“Do These Medications
Help Your Fitness for Battle?”*
Daniel J. Lenihan, MD
Nashville, Tennessee
The use of statins to manage hyperlipidemia and to optimally treat patients with established cardiovascular disease,
hopefully preventing the progression of a host of vascular
conditions, is clearly a major focus of cardiologists worldwide (1). The polypill concept uses a statin in a combination
pill to deliver the most broad administration of critically
important medications. From the vantage point of a
cardiology-centered world, it makes sense to have as complete a distribution of statins to the entire population as
possible, although not all eligible patients can tolerate these
medications.
See page 2384
In this issue of the Journal, researchers from the Cleveland Clinic and Case Western Reserve University use a
case-control observational database to describe the effect of
taking statins during cardiotoxic chemotherapy in patients
with breast cancer (2). Compared with a matched group of
patients who also received similar chemotherapy and did not
take statins, it was clearly demonstrated that patients with
statin use were protected from the development of heart
failure (HF) and had potentially reduced mortality. The
differences between the groups were significant and consistent using a variety of models to understand which patients
may benefit the most. A careful analysis of cardiovascular
risk factors, social determinants of health, number of visits
to both oncologists and cardiologists, other comorbidities,
and cancer treatment details generally indicated that statin
use was connected to improved outcomes. It was also
evident that the presence of cardiac risk factors in patients
undergoing cardiotoxic chemotherapy was associated with
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Division of Cardiovascular Medicine, Vanderbilt University Medical
Center, Nashville, Tennessee. Dr. Lenihan has reported that he has no relationships
relevant to the contents of this paper to disclose.
Vol. 60, No. 23, 2012
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2012.08.1000
the highest hazard ratio for the development of HF, even
higher than the cancer treatment choices. The one area of
detailed treatment information that may have also been
associated with improved outcomes was whether patients
were treated with angiotensin-converting enzyme inhibitors or beta-blockers. Interestingly, the cancer treatment
risks for the development of HF included trastuzumab
administration, not surprisingly, but also higher doses of
cyclophosphamide, a common chemotherapy agent that
is not highly associated with cardiotoxicity. Perhaps these
data suggest that cyclophosphamide is not an innocent
bystander.
The strengths of these data include their thorough
observational nature, similar to a practical registry, with an
excellent description of cardiovascular risk factors. Previously, there has not been a detailed assessment of cardiac
risk factors and comorbidities in a cancer population, and
this information enriches our understanding of how to
prevent and manage cardiac disease in patients being treated
for cancer. Most, if not all, prospective oncology trials do
not have careful cardiovascular risk factor assessment or
typical cardiac treatments delineated throughout the study,
primarily because that is not the focus of these clinical trials.
Additionally, cardiotoxicity in oncology treatment trials is
historically defined by serial reductions in left ventricular
ejection fraction, which limits the definition of cardiotoxicity, and by extension HF, to only those patients who have
systolic dysfunction (3) This study, in contrast, uses International Classification of Diseases-Ninth Revision codes for
HF that are more inclusive than just measurements of left
ventricular ejection fraction for the detection of HF and
cardiotoxicity. The limitations of this in-depth analysis
indicating a benefit for statin use during chemotherapy are
obviously that it was not a randomized, prospectively
blinded study. The possibility that the benefit of statins
demonstrated in this study could be in part related to
additional use of angiotensin-converting enzyme inhibitors
or beta-blockers does add a little uncertainty to determining
the critical element or elements for optimal cardioprotection
during cancer treatment. It would make clinical sense that
angiotensin-converting enzyme inhibitors or beta-blockers
may prevent the development of HF during cardiotoxic
chemotherapy (4), although which therapy is truly cardioprotective on its own would require a prospective randomized study to convincingly establish the recommendation.
Furthermore, using International Classification of DiseasesNinth Revision codes to define cardiac conditions may be
the best that can be done in retrospective studies but is not
as accurate or complete as prospectively defining HF by
acceptable criteria.
Nevertheless, these data are a notable addition to the
published research and illustrate a valuable principle that
cardiology and oncology clinicians should keep in mind.
This principle is that chemotherapy, especially potentially
cardiotoxic chemotherapy such as that based on anthracy-
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Lenihan
Statins in Preparation for Chemotherapy
cline and trastuzumab, is a major cardiovascular stressor,
and all reasonable efforts to enhance cardiovascular reserve
should be undertaken (5). It is also imperative to remember
that patients being treated for cancer are likely to have many
cardiovascular risk factors and/or asymptomatic cardiac disease
that could be exacerbated during aggressive therapy. As a
result, proactive attention is required to give patients their best
chance for excellent outcomes with cancer treatment.
It is well established that statins reduce mortality in
patients with cardiac disease and that cardiovascular disease
is a common condition even in patients with cancer. It
stands to reason that statins would be beneficial in this
population, but it is uncertain how important statins are to
add to any chemotherapy regimen. Clearly, chemotherapy is
stressful, and certain types are especially challenging to the
cardiac system. An enhanced cardiac reserve is beneficial
during cancer therapy, and many potential mechanisms to
improve reserve can be recruited. This report strongly
indicates that statins may be an identifiable and critical
element in recruitable cardiac reserve. The idea that statins
improve cancer outcomes is becoming accepted knowledge
(6). In a manner similar to athletes training to become “fit
for battle” and perform at their peak, statins appear to be a
necessary component for patients with cancer to ready
themselves for their cancer war (7).
JACC Vol. 60, No. 23, 2012
December 11, 2012:2391–2
Reprint requests and correspondence: Dr. Daniel J. Lenihan,
Vanderbilt Heart and Vascular Institute, Division of Cardiovascular Medicine, 1215 21st Avenue South, MCE 5209, Nashville,
Tennessee 37232-8802. E-mail: [email protected].
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in the primary prevention of cardiovascular disease: cost-effectiveness in
the Dutch population. BMJ Open 2011;1:e000363.
2. Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of
statin therapy on the risk for incident heart failure in patients with
breast cancer receiving anthracycline chemotherapy: an observational
clinical cohort study. J Am Coll Cardiol 2012;60:2384 –90.
3. Ewer MS, Lenihan DJ. Left ventricular ejection fraction and cardiotoxicity: is our ear really to the ground? J Clin Oncol 2008;26:1201–3.
4. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol
against anthracycline-induced cardiomyopathy. J Am Coll Cardiol
2006;48:2258 – 62.
5. Jones LW, Haykowsky MJ, Swartz JJ, Douglas PS, Mackey JR. Early
breast cancer therapy and cardiovascular injury. J Am Coll Cardiol
2007;50:1435– 41.
6. Frohlich GM, Rufibach K, Enseleit F, et al. Statins and the risk of
cancer after heart transplantation. Circulation 2012;126:440 –7.
7. Herrera A. The Cancer War: My Story. La Vergne, TN: Lightning
Source, 2004.
Key Words: anthracyclines y breast cancer y heart failure y statins.