0http://www.ncbi.nlm.nih.

gov/pubmed/18001320

The role of statins in heart failure.

Gullestad L1, Oie E, Ueland T, Yndestad A, Aukrust P.

Author information
Abstract
HMG CoA reductase inhibitors (statins) have an established place in the treatment of
coronary artery disease. However, their role in the treatment of heart failure (HF), including
HF due to coronary artery disease, has been controversial since beneficial as well as possible
harmful effects may occur. Several recent studies lend support for a beneficial effect of the
statins in HF. These include: (i) post hoc subgroup analyses of prospective randomized
clinical trials of statin therapy among patients with stable coronary artery disease where
statins reduce the incidence of new HF; (ii) subgroup analysis of the evidence of statin use in
large HF trails with different medication and medical devices; (iii) retrospective observational
studies of statin use in HF; and (iv) prospective randomized clinical trials of statins in nonischemic. Beneficial effects include attenuation of cardiac hypertrophy, improvement in
endothelial function, anti-inflammatory effects, reduction in the activity of matrix
metalloproteinases, reduction in apoptosis, interference with neurohormones, and improved
homeostasis. However, there are also theoretical concerns about statins in HF, and existing
literature for their safety and efficacy in HF patients has been limited by the retrospective or
observational nature of these analyses, examination of incompletely validated surrogate
endpoints and small prospective studies in subgroups of HF subjects. In contrast with the
normal population, low concentrations of LDL and total cholesterol are associated with a
worse prognosis in HF patients and a possible mechanism is reduction in ubiquinone
(coenzyme Q10) levels, which is required for oxidative phosphorylation in cells. The safety
aspect of these drugs in HF patients needs to be answered before statins can be recommended
as a routine drug. For the moment there are several large-scale prospective outcome studies in
HF which probably will give us more definitive answers.

Curr Atheroscler Rep. 2014 Jan;16(1):377. doi: 10.1007/s11883-013-0377-x.

Statin therapy in heart failure: for good, for

bad, or indifferent?
De Gennaro L1, Brunetti ND, Correale M, Buquicchio F, Caldarola P, Di Biase M.

Author information

Abstract
Statins are effective in the prevention of coronary events and the treatment of acute coronary
syndromes. However, their efficacy and safety in patients with heart failure (HF) is still a
matter of debate. On the basis of literature evidence from subgroup analysis, retrospective,
prospective cohort studies, and randomized controlled trials, in this review we try to answer
the following question: Is statin therapy in HF patients for good, for bad, or indifferent?
Some studies showed a negative impact of low cholesterol levels in patients with severe HF
(endotoxin-lipoprotein hypothesis and coenzyme Q10 hypothesis). On the other hand, a large
amount of literature demonstrates that in patients with HF, statins have a positive impact on
survival and other outcomes, regardless of whether the HF was of ischemic or nonischemic
origin, which is related to a combination of mechanisms (pleiotropic effects and cholesterol
reduction). Much of this evidence, however, comes from observational and retrospective
studies and subgroup analyses of statin use in patients with HF. Randomized clinical trials
examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a benefit in
mortality for patients with HF randomized to receive statins. Nevertheless, a meta-analysis
found that statin therapy does not decrease all-cause or cardiovascular mortality but
significantly decreases the rate of hospitalization for worsening HF and increased left
ventricular ejection fraction compared with placebo.
PMID:
24277654
[PubMed - indexed for MEDLINE]

Statin use in heart failure: a cause for

concern?
Raina A1, Pickering T, Shimbo D.

Author information
Abstract
BACKGROUND:

Statins are effective in the prevention of coronary events and the treatment of acute coronary
syndromes. However, their efficacy and safety in patients with heart failure (HF) are
unknown. In this review, we discuss the evidence for the efficacy and safety of statin therapy
in patients with HF.
METHODS:

We reviewed all original English-language, peer-reviewed journal articles published from

1985 to 2005 obtained from a search of the MEDLINE database. We focused on evidence for
the efficacy and safety of statins based on data from patients with HF enrolled in major statin

trials, analysis of the impact of statin use in patients with HF, and randomized clinical trials
examining the effects of statins on cardiovascular outcomes in patients with HF.
RESULTS:

The major primary and secondary prevention statin trials largely excluded patients with HF.
Statin use was also limited in randomized HF trials. Subgroup and retrospective analyses, and
evidence from prospective cohort studies of statin use in patients with HF suggest statins
improve cardiovascular prognosis in HF. The limited small randomized clinical trials also
suggest statins improve symptoms, ejection fraction, and inflammatory biomarkers in patients
with HF.
CONCLUSIONS:

A growing weight of evidence suggests that statins have beneficial effects in HF. At this time,
there is little evidence to support withdrawing or withholding statins from patients with HF.
Ongoing randomized controlled trials that examine the efficacy of statin therapy in patients
with HF should clarify the role of these agents in the context of HF.

Clin Sci (Lond). 2007 Aug;113(3):119-27.

Statins and clinical outcomes in heart

failure.
Martin JH1, Krum H.

Author information
Abstract
HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors (statins) are wellestablished therapies in the prevention and treatment of cardiovascular disease, reducing allcause mortality and cardiovascular events in many disease states. Studies have also suggested
that statins given to patients after myocardial infarction improve event-free survival even in
short time frames; however, evidence for the benefit of statins in established HF (heart
failure) has not been demonstrated with the same rigour of a randomized clinical trial setting.
In fact, clinical data examining the effect of statins in HF have been limited by the
retrospective or observational nature of these analyses, examination of incompletely validated
surrogate end points, small prospective studies in subgroups of HF subjects, and non-uniform
doses and different statins being used. In this review, we examine the evidence for the effect
of statins on mortality in HF, taking into account theoretical arguments, appropriateness of
surrogate markers, animal data and analysis of the predominantly retrospective clinical data
that is currently available.

Curr Heart Fail Rep. 2004 Dec;1(4):156-60.

Do statins prevent heart failure in patients

after myocardial infarction?
Ducharme A1, Rouleau JL.

Author information
Abstract
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, reduce morbidity
and mortality in patients with coronary artery disease (CAD). Because CAD is the major
cause of heart failure (HF) in developed countries, prevention of CAD may result in reduced
HF. Evidence from randomized trials on lipid reduction (Cholesterol and Recurrent Events
and the Scandinavian Simvastatin Survival Study) has shown statins to decrease progression
to HF. Recently, many beneficial effects of statins have been demonstrated beyond
cholesterol lowering. These agents improve endothelial function, exhibit anti-inflammatory
properties, and prevent cardiac hypertrophy. Experimental studies have shown attenuation of
left ventricular remodeling after myocardial infarction, possibly through reduced oxidative
stress. However, no clinical evidence exists to support an effect on ventricular remodeling.
Small, short-lasting clinical studies have also suggested that statin therapy might be
associated with improved survival in ischemic and nonischemic HF.

Drugs. 2006;66(2):145-54.

HMG-CoA reductase inhibitors in chronic

heart failure: potential mechanisms of
benefit and risk.
Laufs U1, Custodis F, Bhm M.

Author information
Abstract
HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and
cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery
disease. However, evidence for statin treatment in patients with chronic heart failure (CHF)
remains a subject of debate. Patients with heart failure were generally excluded in the
existing trials and a different patient population with a distinct pattern of morbidity and
treatment was studied. In addition, no safety data are available for statins in patients with
heart failure, where there are potential concerns about coenzyme Q10 depletion and excessive

low-density lipoprotein reduction. This review summarises the clinical and preclinical
evidence for potential beneficial effects of statins in CHF. In experimental systems, statins
have been shown to improve cardiac function through antioxidative and anti-inflammatory
action. Statins improve endothelial function, may reduce neurohormonal activation, and
stimulate endothelial progenitor cells. Some of these effects occur independently of
cholesterol lowering and can be explained by inhibition of isoprenylation of signal
transducing proteins of the family of Rho guanosine triphosphatases. Two ongoing controlled
randomised trials (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure]
and GISSI-HF [Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure]) will help us to assess whether the described beneficial effects of statins in
heart failure outweigh the potential negative effects and translate into the reduction of clinical
endpoints.

Int J Vasc Med. 2012;2012:162545. doi: 10.1155/2012/162545. Epub 2012 Jun 26.

Effects of statins on cardiorenal syndrome.

Yagi S1, Aihara K, Ikeda Y, Akaike M, Sata M, Matsumoto T.

Author information
Abstract
Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle
as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular
inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is
activated by accumulation of conventional cardiovascular risk factors; however, a strategy for
management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors,
have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular
systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide
bioavailability. Since recent studies have indicated that statins have beneficial effects on
chronic kidney disease and heart failure as well as coronary artery disease in cholesterollowering-dependent/independent manners, treatment with statins might be a successful
strategy for preventing deterioration of CRS.