CORRESPONDENCE: LETTER TO THE EDITOR
A Call for Development of Comprehensive Therapy for Dyslipidemia
Niteen V. Deshpande, MD, DM, DNB, FACC, FESC*,
Harshawardhan M. Mardikar, MD and
Dhananjay Deo, MD
* Cardiac Catheterization Laboratory, Spandan Heart Institute and Research Center, 31, off Chitale Marg, Dhantoli, Nagpur 440012, India (Email: nvdesh{at}hotmail.com).
Treatment of hyperlipidemia with statins has become an integral part of management of vascular disease today. However, numerous gray areas exist in the treatment algorithm. The meta-analysis by Cannon et al. (1) refers to usage of high-dose statin therapy for low-density lipoprotein (LDL) reduction in the treatment of cardiovascular diseases. The title of the study uses the term "Intensive Versus Moderate Statin Therapy," which apparently is a new term being coined for high-dose statin therapy. None of the trials included in the meta-analysis use this term to define the dose of atorvastatin. In all these trials the prime focus was the level of LDL achieved and event reduction following that. The atorvastatin dosage has never been shown to be an independent predictor of long-term outcome in multivariate analysis. Thus, any dose of atorvastatin or any other statin that achieves the desired level of LDL of about 70 mg/dl would be considered as optimal statin therapy according to the current knowledge. Whether the term "intensive" relates to a high dose of atorvastatin or to a dose of statin that reduces LDL to about 70 mg/dl is not clear. Hence, the new term of "intensive statin therapy" is probably not required in today’s clinical jargon.
Whether adequate LDL reduction if achieved using a smaller dose of statins will confer similar benefit as that with high-dose statins is not clear due to lack of data. As the pleiotropic effect cannot be easily measured in clinical practice, the real target for a clinician today is LDL cholesterol. Most of the large-scale trials also use the same target and compare the long-term outcomes with LDL reduction or levels achieved. It would be interesting to perform a subgroup analysis of patients receiving 10 mg of atorvastatin and reaching an LDL target of 70 mg/dl in the trials included in the researchers’ meta-analysis.
It is also very important to understand the same dose of a drug may not be required in all races to achieve the desired effect. In clinical practice in India, most of our colleagues have been able to maintain LDL levels close to 70 mg/dl with much lower doses of atorvastatin. As of today no important trial data is available to us from the region, and thus we rely heavily on Western literature. In this case, what would be an "intensive statin therapy" for an Asian Indian remains a very difficult question to answer. Thus, a term of "optimal lipid-lowering therapy" seems more useful and less confusing than intensive statin therapy.
Low high-density lipoprotein (HDL) is another important contributor to development of atherosclerotic vascular disease. In fact, rapid regression of atheroma has only been shown with infusion of apolipoprotein A-I milano (2). Further, results from the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) study (3) involving 3,086 patients have shown that HDL and not LDL cholesterol levels influence short-term prognosis after acute coronary syndrome (ACS). It is also documented that HDL modulation is better with lower doses of atorvastatin than with higher doses and even better when low-dose atorvastatin is combined with ezetimibe.
Reduction in C-reactive protein is probably the only measurable pleiotropic effect of statins. Comparable C-reactive protein reduction has also been shown with combination of low-dose simvastatin and ezetimibe to that of high-dose atorvastatin, although in a short-term study (4). Reduction in LDL with a combination of low-dose atorvastatin and ezetimibe has been comparable to that with high-dose atorvastatin alone, again in a short-term study (5).
In light of these facts, it is very important that we develop a comprehensive hyperlipidemia therapy that encompasses adequate LDL reduction along with reduction in total cholesterol and triglycerides and elevation of HDL at the same time, rather than harping on high-dose statin therapy.
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References
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1. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy J Am Coll Cardiol 2006;48:438-445.[Abstract/Free Full Text]2. Nicholls SJ, Tuzcu EM, Sipahi I, et al. Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I milano J Am Coll Cardiol 2006;47:992-997.[Abstract/Free Full Text] 3. Olsson AG, Schwartz GG, Szarek M, et al. High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial Eur Heart J 2005;26:890-896.[Abstract/Free Full Text] 4. Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study Am Heart J 2005;149:464-473.[CrossRef][Web of Science][Medline] 5. Ballantyne CM, Houri J, Notarbartolo A, et al. Ezetimibe Study Group Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial Circulation 2003;107:2409-2415.[Abstract/Free Full Text]
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