Statins: Plethora of beneficial effects or is it a myth?

Acute Coronary Syndrome (ACS) refers to combination clinical spectrum,

including acute myocardial infarction and unstable angina, where often associated with
atherosclerotic plaque rupture or thrombotic occlusion (partial/complete) in coronary
arteries.1Following ACS onset, patients have higher recurrent coronary events in 30
days.2 Although large, long-term clinical trials have3 ascertain statin therapy benefits in
cardiovascular events, but in most of the studies, patients with recent ACS were
excluded 6 .Thus, the short-term therapeutic benefit of statin in ACS patients remains
unclear.
Looking into most of trials, statin have exhibited handful benefits. Statins
principally mediate cholesterol-lowering effect by up-regulating LDL receptor activity,
which leads to increase hepatic uptake of atherogenic 2 apolipoprotein B and exhibit
partial inhibition of VLDL synthesis.3 Reduction in LDL level about 29% was observed in
high-dose statin therapy in ACS patients after just 5 days.4 Statin also found to repair
the damaged endothelium by promoting endothelial progenitor cells mobilization and
up-regulate nitric oxide synthase expression. A subsequent increase in NO production
prevents platelet aggregation, reduce leucocyte-endothelium interaction and preserve
endothelial functions. Moreover, statin reduces C-Reactive proteins (enhance monocyte
endothelial adhesion and increases fibrinogen and other coagulative protein level), that
are synthesized in response to cytokine signals that normally originate in inflammation
foci. Pravastatin was found to reduce mean CRP level by 24% after 8 weeks treatment
in ACS patients in a recent trial.1,4 Preclinical evidences also show that statin increase
plaque stability by reducing matrix metalloproteinases expression. 4
Despite significant data supporting early statin therapy benefits in ACS patients,
many questions still needed to be answered. Since statin interferes with cholesterol
synthesis pathway, there is a reduction in compounds deriving from the intermediates.
Reduce formation of ubiquinone can lead to myalgia. Although this is said to be
prevented by intake of coenzyme Q10 supplement, this has not been proven in any
placebo-controlled-clinical-trials.1,4 I believe that new, large-clinical-trials are critically
required to obtain firm results about statins side effect as there are no concrete
evidence on this and to ensure long-term-statin-therapy without doubts.2
Several studies proclaim that statin causes heart rate variability, reduces QR
variability, QTc interval and affects ventricular conduction and excitability by causing
alteration in transmembrane ion channel properties thus reduces ventricular arrhythmia
occurrence. Studies reveal patients who received statins shows a reduction (59%) in
ventricular fibrillation recurrence after 16 months follow-up.5As discussed earlier, statin

reduces both cholesterol level and oxidative stress. This subsequently reduces renin
angiotensin system activity, thus; reduce potential arrhythmogenic substrate for atrial
fibrillation(AF) development. An observational study had demonstrated that statin
therapy was associated with reduced incidence of AF.4,6 Although statin said to induce
VSMC apoptosis which may contribute to plague rupture and consequently promote
recurrent acute coronary events however, this still remain to be proved.7 Therefore,
statin can be said as antiarrhythmic.
Overall, statin have a plethora of beneficial effects as it lowers LDL level, improve
endothelial function, increase plague stabilization, anti-inflammatory, antithrombotic and
act as an antiarrhythmic agent in ACS patients.

(490 words)
References
1. David L Coven, MD, PhD; Chief Editor: Eric H Yang, MD . Acute Coronary
Syndrome. http://emedicine.medscape.com/article/1910735-overview (accessed
24 April 2014).
2. F.M Sacks . Do statins play a role in the early management of the acute coronary
syndrome?. European Heart Journal 2004; 6(A): A32-A36.
http://eurheartjsupp.oxfordjournals.org/content/6/suppl_A/A32.full (accessed 15
April 2014).
3. Andrei C. Sposito, M. John Chapman. Statin Therapy in Acute Coronary
Syndromes :Mechanistic Insight Into Clinical Benefit. Arteriosclerosis,
Thrombosis, and Vascular Biology 2002; 22(): 1524-1534.
http://atvb.ahajournals.org/content/22/10/1524.full (accessed 17 April 2014).
4. Anthony S. Wierzbickia, Robin Postonb, Albert Ferrob. The lipid and non-lipid
effects of statin. Pharmacology and theraupetics 2003; 99(1): 95-112.
http://www.sciencedirect.com/science/article/pii/S016372580300055X (accessed
17 April 2014).
5. Juan Tamargo , Ricardo Caballero, Ricardo Gmez, Luca Nez, Miguel
Vaquero, Eva Delpn. Lipid-lowering therapy with statins, a new approach to
antiarrhythmic therapy. Pharmacology and theraupetics 2007; 114(1): 112.
http://redheracles.net/media/upload/research/pdf/17287023.pdf (accessed 24
April 2014).
6. M.S. Kostapanos , E.N. Liberopoulos, J.A. Goudevenos, D.P. Mikhailidis , M.S.
Elisaf . Do statins have an antiarrhythmic activity?. Cardiovascular Research
2007; (75): 10-20. http://cardiovascres.oxfordjournals.org/ (accessed 14 April
2014).

7. P.O Bonetti , L.O Lerman, C Napoli and A Lerman . Statin effects beyond lipid
lowering -are they clinically relevant?. European Heart Journal 2003; 24(3): 225248. http://eurheartj.oxfordjournals.org/content/24/3/225.full (accessed 14 April
2014).