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Statins in heart failure

 

Clinical bottom line

If current guidelines are funded and followed, the vast majority of patients who are at risk of developing heart failure will in the future be taking a statin anyway, because of their risk of coronary heart disease. The decision will then be whether to stop treatment if they progress to heart failure.


Background

Heart failure is a progressive disease for which the underlying etiology, at least in the western world, is most often coronary heart disease. Patients with symptomatic HF were either excluded or under represented in the major statin outcome trials, but subgroup analyses of 4S and CARE have shown reductions of around 20% in the incidence of new chronic HF for patients treated with statin compared to placebo [1, 2].

There is concern around treating patients with heart failure with statins.

Acute coronary events cause injury to the myocardium and can lead to progression of heart failure. Statins are effective in preventing acute coronary events . In the CARE study [2], left ventricular ejection fraction (LVEF) was recorded, and pravastatin was equally effective in reducing coronary events in patients with LVEF between 25% and 40% as in patients with LVEF greater than 40%. Patients with severe heart fgailure (LVEF less than 25%) were excluded.

Recently statins have been shown to have beneficial effects on the vasculature that are independent of their lipid lowering effects . Potential benefits include improvement of endothelial function and reduced production of inflammatory components. Both endothelial dysfunction and inflammation are significant components of heart failure, irrespective of underlying etiology.

Three recent studies support a role for statins in heart failure.

  1. In 63 patients with symptomatic, non-ischaemic dilated cardiomyopathy, those randomised to simvastatin for 14 weeks showed improvements in cardiac function, neurohormaonal imbalance and markers of inflammation, compared to placebo. These changes correlated with improved symptoms [8].
  2. In a cohort of 551 patients with ischaemic and non-ischaemic heart failure (LVEF 40% or less), statin use was associated with improved survival without the necessity for urgent heart transplantation [9].
  3. A retrospective, analysis of all surviving patients from the OPTIMAAL study (which compared losartan and cpatopril), showed that initiation of b-blocker and statin treatment early after MI complicated by heart failure was associated with reduced morbidity and mortality [10]. The effects of the two treatments were additive. These findings are limited by the retrospective and non-randomised design.

Recent outcome trials in systolic heart failure have reported baseline rates of lipid-lowering therapies of between 11% and 45%, indicating that these agents are becoming widely used in patients with heart failure, presumably because of underlying coronary heart disease. If statins benefit patients with heart failure, then it could be considered unethical to not treat them all, but if they are harmful, then the patients in these trials and others like them should not be receiving them. A prospective randomised trial has been called for. In practice, if current guidelines are funded and followed, the vast majority of patients who are at risk of developing heart failure will in the future be taking a statin anyway, because of their risk of coronary heart disease. The decision will then be whether to stop treatment if they progress to heart failure. The hope is that many fewer will.

References


  1. J Kjekshus et al. The effects of simvastatin on the incidence of heart failure with coronary heart disease. J Card Fail 1997 3: 1079-1082.
  2. SJ Lewis et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Ann Intern Med 1998 129: 681-689.
  3. M Rauchhaus et al. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003 42: 1933-1940.
  4. TB Horwich et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002 8: 216-224.
  5. M Rauchhaus et al. The endotoxin-lipoprotein hypothesis. Lancet 2000 356: 930-933.
  6. M Khatta et al. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med 2000 132: 636-640.
  7. C Hofman-Bang et al. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail 1995 1: 101-107.
  8. K Node et al. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 2003 108: 839-843.
  9. TB Horwich et al. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol 2004 43: 642-648.
  10. A Hognestad et al. Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure. Am J Cardiol 2004 93: 603-606.