Statin therapy in patients with heart failure
- Prakash C Deedwania, MD
Prakash C Deedwania, MD
- Professor of Medicine
- University of California San Francisco School of Medicine
Statin therapy is widely used for both the secondary and primary prevention of atherosclerotic cardiovascular disease. However, the randomized trials that have provided evidence of benefit have included few patients with heart failure (HF) [1,2]. However, two major randomized trials, CORONA and GISSI-HF, have directly addressed this issue in patients with systolic HF. In addition, HF management is potentially complicated by the observation that low serum cholesterol is associated with worse outcomes.
These issues will be reviewed here. The role of statin therapy in the broad group of patients with cardiovascular disease and the multiple mechanisms by which statins might act in addition to cholesterol lowering are discussed elsewhere. (See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention" and "Statins: Actions, side effects, and administration" and "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease".)
SERUM CHOLESTEROL AND PROGNOSIS IN HF
A low serum cholesterol in patients with heart failure (HF) is associated with higher mortality [1,3,4]. The following observations illustrated the range of findings:
●In a retrospective review of 1134 patients with advanced, chronic HF (almost all New York Heart Association [NYHA] class III or IV) (table 1), mean left ventricular ejection fraction [LVEF] 22 percent), the serum cholesterol was higher in survivors compared to nonsurvivors at one year . Patients in the lowest quintile of serum cholesterol (<129 mg/dL [3.3 mmol/L]) had an adjusted relative mortality risk of 2.1 compared to those in the highest quintile (serum cholesterol >223 mg/dL [5.8 mmol/L]). Low cholesterol appeared to be a marker for more severe disease, since these patients also had other findings known to predict worse outcomes in patients with HF, including lower serum albumin, lower serum sodium, and lower LVEF. (See "Predictors of survival in heart failure due to systolic dysfunction" and "Prognosis of heart failure".)
●A relationship between lower serum cholesterol levels (less than 200 mg/dL [5.2 mmol/L] and higher mortality was also found in a multivariable analysis of 114 patients with chronic HF . The multivariable model was validated in a second group of 303 additional patients with HF. The findings were independent of the etiology of HF.
- Deedwania PC, Javed U. Statins in heart failure. Cardiol Clin 2008; 26:573.
- Foody JM, Shah R, Galusha D, et al. Statins and mortality among elderly patients hospitalized with heart failure. Circulation 2006; 113:1086.
- Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002; 8:216.
- Rauchhaus M, Clark AL, Doehner W, et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003; 42:1933.
- Horwich TB, Hernandez AF, Dai D, et al. Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. Am Heart J 2008; 156:1170.
- Ramasubbu K, Estep J, White DL, et al. Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy. J Am Coll Cardiol 2008; 51:415.
- Masoudi FA. Statins for ischemic systolic heart failure. N Engl J Med 2007; 357:2301.
- Sola S, Mir MQ, Lerakis S, et al. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 2006; 47:332.
- Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis. Lancet 2000; 356:930.
- Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol 2008; 52:1435.
- Horwich TB, MacLellan WR, Fonarow GC. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol 2004; 43:642.
- Scirica BM, Morrow DA, Cannon CP, et al. Intensive statin therapy and the risk of hospitalization for heart failure after an acute coronary syndrome in the PROVE IT-TIMI 22 study. J Am Coll Cardiol 2006; 47:2326.
- Khush KK, Waters DD, Bittner V, et al. Effect of high-dose atorvastatin on hospitalizations for heart failure: subgroup analysis of the Treating to New Targets (TNT) study. Circulation 2007; 115:576.
- Domanski M, Coady S, Fleg J, et al. Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]). Am J Cardiol 2007; 99:1448.
- Krum H, Ashton E, Reid C, et al. Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail 2007; 13:1.
- Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357:2248.
- Cleland JG, McMurray JJ, Kjekshus J, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol 2009; 54:1850.
- Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372:1231.
- Fonarow GC. Randomized clinical outcome trials of statins in heart failure. Heart Fail Clin 2008; 4:225.
- Fukuta H, Sane DC, Brucks S, Little WC. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005; 112:357.