To treat or not to treat with statins patients with chronic heart failure?

Czech version

Authors: J. Hradec
Authors‘ workplace: III. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
Published in: Vnitř Lék 2009; 55(9): 802-807
Category: 80th Birthday - prof. MUDr. Miloš Štejfa, DrSc., FESC

Overview

Two clinical trials – CORONA and GISSI-HF – have been conducted to resolve uncertainties about the effects of statins in patients with chronic heart failure and justified suspicions that treatment with statins in these patients might be detrimental. The CORONA trial researched the effects of 10 mg rosuvastatin compared to placebo on the incidence of serious cardiovascular events in 5,011 patients with systolic heart failure of ischemic aetiology, above 60 years of age and in the NYHA functional class II–IV. Even though rosuvastatin reduced the mean LDL-cholesterol plasma concentrations by 45.0% (p < 0.001) and high-sensitivity C-reactive protein (hsCRP) concentrations by 37.1% (p < 0.001), the incidence of cardiovascular events was not importantly affected (HR = 0.92; p = 0.12). Rosuvastatin had no effect on overall mortality. The treatment resulted only in a reduction of the number of hospitalizations for cardiovascular causes (p < 0.001). The GISSI-HF trial involved 4,574 patients with chronic heart failure irrespective of aetiology and the ejection fraction value randomised to take either 10 mg of rosuvastatin or placebo. The results were almost identical. Rosuvastatin had no effect on the incidence of the primary end-point – the sum of cardiovascular mortality and hospitalizations (HR = 1.01; p = 0.903). The overall mortality was not affected either. Administration of rosuvastatin in both studies was safe, the number of adverse events, including myopathies and renal failure, was no different from placebo. However, recent results from the CORONA trial subtrials have suggested that important interactions exist in patients with chronic heart failure between the effects of rosuvastatin and natriuretic peptide and hsCRP plasma concentrations. Rosuvastatin provides clinical benefit in patients with relatively low concentrations of natriuretic peptides, i.e. relatively well-controlled, while it has no clinical effect in patients with high natriuretic peptide concentrations. Similarly, rosuvastatin provides clinical benefit in patients with high hsCRP but has no effect in patients with normal hsCRP (< 2 mg/l).

Key words:
CORONA study – GISSI-HF trial – rosuvastatin – chronic heart failure – hsCRP – natriuretic peptides

Sources

1. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–1389.

2. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and deaths with pravastatin in patients with coronary artery disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–1357.

3. Sachs FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol level. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001–1009.

4. MRC/BHF Heart Protection Study Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–33.

5. Anker SD, Clark AL, Winkler R et al. Statin use and survival in patients with chronic heart failure – results from two observational studies in 5200 patients. Int J Cardiol 2006; 112: 234–242.

6. Horwith TB, Hamilton MA, MacLellan WR et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002; 8: 216–224.

7. Rauchhaus M, Clark AL, Doehner W. The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003; 42: 1933–1940.

8. Shepherd J, Mlauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–1630.

9. Kjekshus J, Apetrei E, Barrios V et al for the CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007; 357: 2248–2261.

10. GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1231–1239.

11. Hradec J. Studie CORONA. Máme podávat statiny nemocným se srdečním selháním? Remedia 2008; 18: 176–179.

12. Hradec J. Má význam podávání statinů u nemocných se srdečním selháním? Interní Med 2008; 10: 216–218.

13. Cleland J et al. Interaction between the effects of rosuvastatin and plasma concentrations of NT-proBNP. Předneseno na Výročním kongresu ESC 2008, Mnichov.

14. McMurray J, Kjekshus J, Gullestad L et al. Effects of statin therapy according to plasma high sensitivity C-reactive protein concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA): a retrospective analysis. Circulation 2009; v tisku.