INTRODUCTION
Studies on the prevalence of Coronary Heart Disease (CHD) in India reveal that this disease is zooming in a linear if not exponential manner. In 1960, every 25th individual in India could be suspected of having CHD, whereas in 2001, every ninth adult Indian could be a victim. Moreover, cardiovascular risk factors cluster among Indians and include a high prevalence of diabetes, higher insulin resistance, abdominal obesity, hypertriglyceridemia, low levels of high density lipoprotein (HDL), high prevalence of small dense low density lipoprotein (LDL), increased fibrinogen levels and lipoprotein (a) [Lp (a)] levels.


MOVING BEYOND LDL
Over the years, the statin group of drugs, which mainly target LDL, have been shown to bring about a significant reduction in coronary mortality and morbidity. However, the magnitude of reduction in coronary events achieved by statins in landmark trials is only 30%. This indicates that there is a need to move beyond LDL and consider other risk factors such as elevated triglycerides, low levels of HDL, elevated levels of small dense LDL, elevated fibrinogen levels and increased Lp (a) levels. All these factors have now been shown to be independently associated with CHD risk.


THE FIBRATE RENAISSANCE
The first fibrate, clofibrate was described in 1962. This class was widely used until the advent of statins, which subsequently gained wide popularity due to their potent LDL lowering properties. However, new understanding regarding other independent CHD risk factors besides elevated LDL, especially elevated triglycerides and low HDL, has now led to a resurgence of the fibrate class.


FENOFIBRATE MAIN EFFECTS
Recent data suggest that many of the beneficial lipid-modifying effects of fenofibrate are mediated via peroxisome proliferator activated receptor-a (PPAR-a). Via this mechanism, fenofibrate markedly reduces triglyceride levels with changes ranging from 29% to 58%.

Fenofibrate also increases HDL levels by 15% to 30%. When baseline HDL is < 35 mg/dl, the increase is more pronounced and may reach 40% to 50%.

Fenofibrate also induces a moderate reduction in LDL by 20% to 35% and total cholesterol by 17% to 29%. It also reduces levels of the atherogenic small dense LDL.

Beneficial effects on levels of lipoprotein (a) and fibrinogen have also been documented with fenofibrate. The drug also decreases levels of uric acid, a possible risk factor for CHD.

Fenofibrate also improves insulin sensitivity.


DAIS TRIAL
The Diabetes Atherosclerosis Intervention Study (DAIS), a landmark trial, was conducted (mean follow-up 39 months) to examine specifically whether correcting lipid abnormalities with micronised fenofibrate in type 2 diabetes would alter the progression of CHD.

Compared with placebo, treatment with micronised fenofibrate resulted in a significant correction of the lipid abnormalities typically seen in type 2 diabetes viz. high triglycerides, low HDL and increased levels of small dense LDL. Importantly, fenofibrate decreased progression of CHD by 40%.

COMPARISON WITH STATINS
While statins cause a greater reduction in LDL, fenofibrate causes a greater reduction in triglycerides (Table). The effects of fenofibrate on HDL are also significantly greater than statins (which increase HDL by 5% to 10%). Fenofibrate also decreases fibrinogen and Lp(a) levels, which are largely unaffected by statins.


SAFETY
In general, fenofibrate is well tolerated. Most frequently reported effects are gastrointestinal, occurring in approximately 5% of patients.

Significant increase in liver enzymes have been reported in less than 2% of patients.


STATIN - FIBRATE COMBINATION
Since statins and fibrates have complementary effects, it would be useful to combine the two
classes of drugs, especially in Indian patients due to the lipid abnormalities involved. In the past, concern has been voiced that the use of fibrate-statin combination may increase the risk of myopathy.

However, more recent studies using statins (in low doses) in combination with fibrates have shown that the combination is well tolerated; the risk is not markedly increased as compared to monotherapy. However patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Creatine phosphokinase (CPK) levels should be assessed in patients reporting these symptoms, and therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed.


INDICATIONS AND DOSAGE
Fenofibrate is indicated in hypercho-lesterolemia, hypertriglyceridemia
and mixed dyslipidemia. The recommended dosage of micronised fenofibrate is 200 mg per day with meals.


CONCLUSION
Micronised fenofibrate is an effective lipid-regulating agent, which causes a decrease in LDL and total cholesterol levels, a marked reduction in elevated triglycerides levels and a significant increase in HDL levels. The use of fibrates, such as fenofibrate, would help in countering other CHD risk factors and, thus play an important role in the effective management of CHD, especially in the Indian context.

Drug class	Effect on total cholesterol	Effect on LDL cholesterol	Effect on HDL cholesterol	Effect on triglycerides	Effect on fibrinogen	Effect on Lp(a)
Statins
Fibrates
no change     decrease     increase