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To the Editors:
I appreciated the topic addressed in the Cardiology Casebook column titled "Statin Therapy in Congestive Heart Failure" (2005;14:338–340); however, I am concerned with several points in the case. When listing the medications the patient was taking, the authors noted that eplerenone was prescribed at a dose of 50 mg twice a day when in fact the recommended dose, and doses used in the clinical trial for heart failure, is 50 mg daily. In reality, enalapril should be administered at a target does of 20 mg twice a day.
If utilizing evidence-based medicine, the answer to the first question, "Which one of the following medications is vital to the management of CHF [congestive heart failure]?" should be angiotensin-converting enzyme inhibitors, ß-blockers, and aldosterone receptor blockers. These medications have all been shown to improve morbidity and mortality. Diuretic therapy in CHF has never been shown in clinical trials to improve mortality, though it has been shown to provide symptom relief. Therefore, when asking what medication is vital to CHF management, I think that the answer provided is incorrect. Stating that a diuretic is the "best and most effective therapy in treating CHF" is based on symptom relief and not on long-term outcomes such as mortality.
In the discussion on lipid management, the authors stated that low-density lipoprotein (LDL) levels as low as 50 have been shown to reduce coronary events and mortality. The reference listed for this data was a study of a rat with heart failure. The current recommendations for humans, based on the National Cholesterol Education Program (NCEP) guidelines, is a goal of 70 or less in very high-risk patients—and I believe the patient discussed in the Cardiology Casebook was high risk. No prospective, randomized clinical trial data exist that identify an LDL goal of 50. The recent PROVE-IT and TNT trials clearly demonstrated benefits for lower LDL levels in the 70 range. The recent update from the NCEP with the high-risk goal of 70 stemmed from these trial results.
Norton, Ohio
The Authors Reply
The insightful concerns in Rebecca L. Angerstein’s letter are appreciated. Our responses to her concerns follow. First and foremost, in order of clinical significance we consider the control of the sodium ion crucial and primary in the clinical care of congestive heart failure (CHF). It is noteworthy that the earliest response in the initial onset of CHF is an increase in heart rate in support of a decrease in cardiac output; this is quickly followed by Na+ preservation with water retention, referred to as "priming the pump." If treatment to reduce Na+ and water is not initiated, the consequences are peripheral edema and ultimately progression to anasarca. No matter what the etiology of CHF, whether congenital or acquired, CHF cannot be adequately treated without primary attention to the critical role of Na+ and therapy to initiate natruresis and limit dietary salt intake. The role of Na+ and water in CHF is underscored by the physical test for the presence of a "hepatic reflux," the last physical sign to become normal when full cardiac compensation is achieved. A positive test indicates an increase in hepatic fluid volume and thus evidence of the continued presence of CHF, and providing additional evidence for the role of fluid in assessing the degree of CHF, and effectiveness of therapy. To date, levels of brain natriuretic peptide have not been equated with the signs of hepatojugular reflux, viz: the degree of or recovery from CHF. ß-Blockers, angiotensin-converting enzyme inhibitors and/or blockers, and aldosterone receptor blockers, listed in order of importance in managing CHF, are nevertheless "icing on the cake" in comparison to diuretic therapy and Na+ restriction. The etiology of CHF should not influence the basic treatment of fluid overload common to all forms of CHF. In fact, the term "congestive," which precedes "heart failure," implies water or fluid retention. Failure will beget failure and CHF will progressively worsen when volume retention common in CHF is not adequately treated with diuretics and low Na+ diet. This is not to disregard the importance of treating the etiology of CHF by improving coronary circulation or correcting valvular abnormalities. Nevertheless, in patients with CHF, natruresis and reducing cardiac demands by modifying activity will initiate cardiac compensation regardless of etiology. Compensation can be accomplished with diuretics, Na+ restriction, and reducing demands for cardiac work in patients in whom direct improvement in myocardial function is not possible (eg, the elderly in whom CHF is most frequent and where surgical revascularization is deemed to be too risky). We would strongly disagree with any report in the literature that disregards the major role of Na+ and the significance of a low Na+ diet and diuretic therapy in attaining cardiac compensation in CHF, a view that is contrary to the long established principles in treating CHF. The use of diuretics is the cornerstone of successful therapy for CHF.
The Physicians’ Desk Reference (PDR) 2005 clearly indicates that eplerenone dosage can be 50 mg twice a day. Regarding the question of enalapril dosage, each patient requires dose titration starting with 5 mg daily. Many cannot tolerate a 40 mg daily dose of enalapril. This is emphasized in the cardiac and renal literature; in addition, precautions in the dosage of enalapril are stressed in the PDR 2005.
The serum levels of low-density lipoprotein cholesterol (LDL-C) for which statin therapy is indicated has had an interesting history over the years. In answer to concerns regarding therapeutic guideline references for statin therapy, the following can be gleaned from the literature. The HMG-CoA reductase inhibitors (statins) were approved by the Federal Drug Administration in 1987. In 1990, the recommended therapeutic aim for LDL-C was 135 mg/dL for those with no history of coronary disease and 100 mg/dL for those with a history of coronary disease. In 1995, 100 mg/dL was the recommended goal for LDL-C regardless of the past history.
The following are guidelines used to refine treatment for atherosclerosis (from the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults):
1990 - goal for LDL-C 130 mg/dL
1993 - ATP-II goal for LDL-C with coronary heart disease <100 mg/dl
ATP-II goal for LDL-C without coronary heart disease and less than 2 risk factors <130 mg/dL
ATP-II goal for LDL-C without coronary heart disease and 0 to 1 risk factors <160 mg/dL
2001 - ATP-III without coronary disease <130 mg/dL
2005 - LDL-C 70 mg/dl goal in treating hyperlipidemia.
Isolated reports have shown that an LDL-C level of 60 mg/dl offers greater protection, endothelial cell repair, and can be achieved without undue side effects of an increase in statin dosage. Note the continued downward trend in target levels of LDL-C over 15 years of statin therapy. LDL-C levels of 40 to 50 mg/dl are the author’s (Dr Lemberg) goals for patients with multiple coronary disease risk factors or high hs-CRP and 15 years experience in the use of statins in treating hyperlipidemia. Our personal recommendations to our readers regarding the optimal LDL-C level for prevention and treatment of atherosclerotic heart disease: "STAY TUNED," "lower is better," and the lowest therapeutic level for LDL-C has yet to be established!
Finally, the rat, an unduly maligned but very useful laboratory animal, has served the medical profession admirably and has been employed extensively for years in numerous pharmaceutical dosage safety tests! (reference PDR 2005, as well as in every annual PDR of previous years)
BIBLIOGRAPHY
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