Hyperlipoproteinaemia and dyslipoproteinaemia II. Therapy: Non-pharmacological and pharmacological approaches

Česká verzia

Authors: R. Češka; S. Krutská; L. Kašná; G. Šmelková; L. Zlatohlávek; M. Vráblík
Authors place of work: Centrum preventivní kardiologie III. interní kliniky 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
Published in the journal: Vnitř Lék 2010; 56(7): 647-654
Category: 80th Birthday - Jaroslava Blahoše, MD, DrSc.

Summary

At present, literally no one disputes hyperlipoproteinaemia and dyslipidemia (HLP and DLP) treatment as a rational therapeutic approach in the prevention of cardiovascular diseases (CVD). This approach is in line with the current principles of evidence-based medicine (EBM) and is sufficiently evidenced particularly by the results of large intervention studies. Nevertheless! When the results of the recent studies are critically appraised, these by no means are (mostly, there, obviously, are exceptions) as conclusive as the studies conducted in 1980s and 1990s. Consequently, positive results are being sought in subanalyses, subgroup evaluations and multiple-study metaanalyses. This paper is not intended as a critique of new drugs. These certainly are developed to be safe, effective and well-tolerated. However, the newer studies suffer from a range of issues: the populations studied are already very well managed, it is not possible to compare against placebo and sometimes, let us be honest, the trial design itself is problematic (often it is an uncritical effort to treat as wide as possible range of patients as well as new groups of patients who might not be suitable for the given treatment). Certainly, we should not start disputing the well-evidenced hypotheses and seek alternatives to the long-established arguments and approaches as a consequence to some less convincing studies. We must not overlook the most robust results of statin studies as well as ‘positive’ studies with other hypolipidemics. There is no doubt that the effect of statins on LDL-cholesterol represents a significant move towards cardiovascular disease prevention. Despite this, we currently recognise with increased intensity that this very effective and well-evidenced treatment has its limits and that a high proportion of patients dies or are faced with cardiovascular diseases even though they are treated with a correct dose of a statin and a target LDL-C level is achieved. This remaining risk (represents more than 50% of events) has been termed ‘RESIDUAL RISK’. The issue of residual risk is crucial in patients with type 2 diabetes mellitus (DM2T) or in all patients with HDL-C-low DLP. As was repeatedly emphasised, a statin will be a cornerstone of pharmacological treatment of a DLP. However, a question arises what to combine it with. The most convincing data exist for niacin (combination of niacin with laropiprant minimising the incidence of unwanted flushes). We surely should not marginalize other hypolipidemics used mainly in combinations: resin and ezetimibe to treat LDL-C, niacin, fibrates and possibly ω-3-fatty acids to manage the residual risk (HDL and TG). Last but not least we should not forget non-pharmacological treatment as the pivotal treatment approach in all patients.

Key words:
diet – statins – niacin – resin – ezetimibe - fibrates

Zdroje

1. Kassan M, Montero MJ, Sevilla MA. Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats. Br J Pharmacol 2009; 158: 541–547.

2. Ridker PM, Rifai N, Pfeffer MA et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98: 839–844.

3. Ridker PM, Morrow DA, Rose LM et al. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low‑density lipoprotein cholesterol < 70 mg/dl and C‑reactive protein < 2 mg/l: an analysis of the PROVE‑IT TIMI‑22 trial. J Am Coll Cardiol 2005; 45: 1644–1648.

4. Vetrugno V, Di Bari MA, Nonno R et al. Oral pravastatin prolongs survival time of scrapie‑infected mice. J GenVirol 2009; 90: 1775–1780.

5. Redecha P, van Rooijen N, Torry D et al. Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. Blood 2009; 113: 4101–4109.

6. Executive summary of the third report of the NCEP expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA 2001; 285: 2486–2497.

7. Haffner SM. Coronary heart disease in patients with diabetes. N Engl J Med 2000; 342: 1040–1042.

8. Keech AC, Mitchell P, Summanen PA et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007; 370: 1687–1697.

9. Svačina Š. Metabolický syndrome. Praha: Triton 2001.

10. ADA, NHLBI, AHA et al. Diabetes mellitus: A major risk factor for cardiovascular disease. Circulation 1999; 100: 1132–1133.

11. O’Keefe JH Jr, Miles JM, Harris WH et al. Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clin Proc 1999; 74: 171–180.

12. Češka R et al. Cholesterol a ateroskleróza. Léčba dyslipidémií. Praha: Triton 2005.

13. Shepherd J. Combined lipid lowering drug therapy for the effective treatment of hypercholesterolemia. Eur Heart J 2003; 24: 685–689.

14. Brousseau ME, Schaefer EJ, Wolfe ML et al. Effects of an inhibitor of cholesteryl ester transfer protein in HDL cholesterol. N Engl J Med 2004; 350: 1505–1515.

15. Mazzone T. HDL cholesterol and atherosclerosis. Lancet 2007; 370: 107–108.

16. Qin S, Koga T, Ganji SH et al. Rosuvastatin selectively stimulates apo A‑I but not apo A‑II synthesis in Hep G2 cells. Metabolism 2008; 57: 973–979.

17. Ballantyne CM, Raichlen JS, Nicholls SJ et al. Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasound‑derived coronary atheroma burden. Circulation 2008; 117: 2458–2466.

18. Robins SJ, Collins D, Wittes JT et al. Relation of gemfibrozil treatment and lipid levels with major coronary events, VA‑HIT: A randomized controlled trial. JAMA 2001; 285: 1585–1591.

19. Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin and pravastatin across doses (STELLAR Trial). Am J Cardiol 2003; 93: 152–160.

20. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoproteid cholesterol, ischaemic heart disease and stroke: systematic review and meta‑analysis. BMJ 2003; 326: 1423.

21. Sacks FM. Low‑density lipoprotein lowering therapy: an analysis of the option. J Am Coll Cardiol 2002; 40: 2135–2138.

22. Shepherd J. Combined lipid lowering drug therapy for the effective treatment of hypercholesterolemia. Eur Heart J 2003; 24: 685–689.

23. Davidson MH, McGarry T, Bettis R et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002; 40: 2125–2134.

24. Keating GM, Robinson DM. Rosuvastatin: a review of its effect on atherosclerosis. Am J Cardiovasc Drugs 2008; 8: 127–146.

25. Fruchart JC, Sacks F, Hermans MP et al. The residual risk reduction initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am J Cardiol 2008; 102 (Suppl 10): 1K–34K.

26. Fruchart JC, Sacks F, Hermans MP et al. The residual risk reduction initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. Diab Vasc Dis Res 2008; 5: 319–325.