Hypertriglyceridemia: A Review of Clinical Relevance and Treatment Options: Focus on Cerivastatin

Hans-Willi M. Breuer, Abteilung für Innere Medizin, St. Carolus-Krankenhaus Görlitz, Carolusstr. 212, 02827 Görlitz, Germany 

Curr Med Res Opin. 2001;17(1):60-73. 

In This Article

Patient Management

Before considering which treatments are most effective in reducing the TG level, there is a need to determine whether reducing Tgs in itself actually has a beneficial effect - i.e. does lowering TG level actually reduce the risk of CHD?

Hypertriglyceridemia is most often seen inpatients with combined type Iib hyperlipidemia,making it difficult to assess the clinical relevance of reducing TG levels in isolation from other lipid parameters. The presence of other disorders may also cloud the picture. In type 2 diabetes and long-term glucose metabolism disorders, for example, the lipid profile tends to be high TG, low HDL-C and normal LDL-C concentrations[3,52]. Reducing TG levels in these patients may have a marked effect on CHD risk reduction[3,52].

A reduced risk of CHD post-therapy observed inpatients with normal LDL-C levels and high baseline TG may be due to a reduction in TG levels. Some recent post-hoc analyses of the results from the Cholesterol and Recurrent Events (CARE) trial and the West of Scotland Coronary Prevention Study(WOSCOPS)[67,68] have indicated that lowering LDLC levels below a certain value does not reduce the rate of coronary events. However, a correspondingpost-hoc analysis of the 4S study[69] indicates no such threshold. This interpretation is more consistent with the results from epidemiological studies. These findings may indicate that more emphasis should be put on improving the complete lipid profile, also increasing HDL-C and reducing TG levels, to improve clinical outcome.

Landmark clinical endpoint statin trials[46,67,70] have shown that clinical improvement correlates strongly with LDL-C reduction and this remains the primary treatment goal[46,67,68,69,70]. TG is also reduced but the degree of clinical significance of this change is not known. Some trial data have shown that a reduction in TG without a reduction in LDL-C does not correlate with a reduction in coronary events[45], but this has not been confirmed in other trials. Manystatin landmark studies[67,68,69] have shown that there is a correlation between baseline TG and the incidence of coronary events, but an association between a reduction in TG and a reduction in CHD risk independent of LDL-C reduction, TC reduction and HDL-C increase, has not been proven.

Fibrate clinical endpoint trials, the BIP(Bezafibrate Intervention Prevention Trial)[71,72,73] and the VA-HIT (Veterans Affairs HDL Intervention Trial)[74], showed no correlation between TG levels and CHD events. Subgroup analysis of the VA-HIT data is ongoing to determine whether other issues have obscured the TG effect on CHD events.Although both trials demonstrated significant

reductions in TG and increases in HDL-Cconcentrations, the correlation with a reduction in cardiovascular risk was not significant[45].Some trials[58] have shown that an increase in HDLC and a reduction in TG level in patients with a high TG pre-therapy baseline led to significant reduction in adverse coronary events. However, the clinical significance of reducing TG levels in isolation is not proven.

In the HHS study, fibrate therapy reduced risk for CHD in patients with type IIb hyperlipidemia. In the Stockholm Ischemic Heart Disease study[75], a combination of fibrates and nicotinic acid reduced mortality, again mainly in patients with high baseline TG levels.

Patients with severe hypertriglyceridemia, TG> 5.6-13.2 mmol/l (> 500-1000 mg/dl), are at risk of acute pancreatitis (type V, associated with increased chylomicrons and VLDL-C). In these cases, fibrate or nicotinic acid and diet control is the most effective therapy[6,61].

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