Elaine C. Payumo, M.D., F.P.C.P., F.P.C.C.Danilo S. Santos, M.D., F.P.C.P., F.P.C.C.

Danilo S. Kuizon, M.D., F.P.C.P., F.P.C.C., F.A.C.C.

ABSTRACT Background: Hypertriglyceridemia is a common form of

dyslipidemia that is usually correlated with cardiovascular dis-

eases including the occurrence of an acute coronary syndrome or

the need for a coronary intervention. Of all anti-lipidemic drugs,

fenofibrates exert the highest lowering of triglycerides by as

much as 40% to 50%. Likewise fibrates lower serum cholesterol as

much as 20% to 25%, increase by HDL 10-20% and decrease LDL by

5-25%. Fenogal is one such fibrate, that is uniquely formulated

in lidose technology, which combines the advantages of a capsule

and a liquid. At 37oC in-vivo, a very fine emulsion is formed coat-

ing the gastric mucosa thereby enhancing bioavalability of active

ingredients and reducing risks of gastrointestinal side effects.

In addition a good mass and drug content uniformity is formed.

Lidose protects the active ingredient against oxidation.

General Objective:

To determine the efficacy and safety of fenofibrates particularly

Fenogal (lidose technology) in dyslipidemic patients.

Specific Objective: (1.) To determine the efficacy of Fenogal

in decreasing triglycerides, total cholesterol, and LDL; while in-

creasing HDL. (2.) To determine the safety of the lidose tech-

nology using clinical parameters, biochemical profile, and side

effects

Methodology: This was an open labeled study of Fenogal

160 mg once daily involving adult out-patients of cardiologists

and internist in all over the Philippines who have hypertriglyceri-

demia, hypercholesterolemia, or both from August 2007 to May

2009. Previous medications for dyslipidemia of patients were

discontinued. Demographic data of patients were based upon

OPD charts. Assessment of lipid parameters (total cholesterol,

triglycerides, LDL, and HDL) were taken at baseline, week 4, and

week twelve. Blood pressure, heart rate, and biological markers

(SGOT, SGPT, alkaline phosphatase, and FBS) were also measured

at same interval.

Statistical Analysis: Continuous data such as age, weight,

and height were described using mean and SD. Categorical data

were presented in frequency and percent distribution. To deter-

mine the significance of change in the different outcome vari-

ables, paired t-test was applied to the data. A p-value ≤ 0.05 was

considered significant.

Results: There were 3,000 patients included in this open

Introduction: Cardiovascular diseases are the main causes of mortality

and morbidity in the industrialized countries. The presence of

atherosclerosis is associated with 50% of myocardial infarctions,

and 70% of deaths due are to cardiovascular diseases. Major epi-

demiological studies showed that the modification of the plasma

lipoproteins profile has major beneficial effects on mortality and

morbidity related to cardiovascular diseases.1,2

It is therefore imperative to focus on risk factors modifica-

tion. Included among the most important modifiable risk factors

label study with a mean age of 52 ± 11.60 years, and almost

equal number of males (50.6%) and females (49.0%). However,

there were 10 patients with gender not indicated. More than

half (50.2%) of the patients had both hypercholesterolemia and

hypertriglyceridemia. Fenogal significantly decreased total cho-

lesterol by 9.91% after 4 weeks of treatment and by 16.37% af-

ter 12 weeks (p=0.000). LDL likewise significantly decreased by

8.15% after 4 weeks of treatment and by 15.91% after 12 weeks

(p=0.000). HDL significantly increased by 15.64% after 4 weeks

and by 23.51% after 12 weeks (p=0.000). Trigylcerides decreased

significantly by 20.72% after 4 weeks and by 33.15% after 12

weeks (p=0.000). FBS decreased significantly by 10.12 mg/dl at

4 weeks of treatment (p=0.000) and by 13.34 mg/dl at 12 weeks

of treatment (p=0.000).

The systolic blood pressure decreased significantly by a mean

of 10-14 mmHg as well as the diastolic blood pressure by a mean

of 6-8 mmHg (p=0.000). There was a significant decrease in heart

rate by a mean of 1.3-1.8 bpm (p=0.000)

There was no significant change in the SGOT (p=0.30 at 4

weeks and p=0.326 at 12 weeks) and SGPT (p=0.817 at 4 weeks

and p=0.945 at 12 weeks).

The adverse event rate was 1.1% and was mostly gastrointes-

tinal related. Bloatedness was the most common complaint.

Conclusion: The authors conclude that Fenogal (lidose tech-

nology) is effective in improving the lipid profile of dyslipidemic

patients, and can be safely and effectively used among Filipino

patients. Increase in alkaline phosphatase needs further inves-

tigation. The improvement in blood pressure, FBS, and heart

rate may reflect the patient’s overall change in lifestyle brought

about by the physician’s recommendation for such a change.

1

are dyslipidemia, diabetes mellitus, obesity, and hypertension.

In all of these risk factors, an important characteristic abnormal

level of plasma lipids is seen.

Various anti-lipidemic drugs are available. Among these,

statins are considered the first line of treatment for cholesterol

control. Side effects of statins are very well known.3 Hypertrig-

lyceridemia is a common form of dyslipidemia that is usually cor-

related with cardiovascular diseases, which is generally defined

by the occurrence of an acute coronary syndrome or the need for

a coronary intervention.

Fenofibrates can lower both triglycerides by 40% to 50%, and

serum cholesterol as much as 20% to 25%. Cholesterol reduction

is obtained by lowering low density atherogenic factors such as

VLDL and LDL. It is a known fact that the directly proportional

relationship between hypercholesterolemia and atherosclerosis

existed and has been well established. However, low level of HDL

is also associated with an increased coronary risk. Considering all

other factors, increased triglyceride level is also associated with

increased vascular risk.4,5,6

Fenogal in lidose technology combines the advantages of a

capsule and a liquid. When in contact with a physiological me-

dium at a temperature of 37oC, it forms a very fine emulsion

that coats the gastric mucosa (one dose produces approximately

50 micro micelles droplets). Lidose enhances bioavailability of

active ingredients and it reduces risks of gastrointestinal side

effects.

With its IUPAC name of: propan-2-yl 2-[4-(4-chlorobenzoyl)

phenoxy]-2-methylpropanoate.

It is a hard capsule with a semi-solid content in which fenofi-

brate 160mg is homogeneously dispersed within a mixture of lipid

excipients. A hydroxypropylcellulose type of polymer is present

to prevent any formation of fenofibrate crystal when exposed to

gastrointestinal fluids, and it is continuously released by a diffu-

sion-erosion process. This technology has enhanced bioavailabil-

ity as compared to the standard formulation.

Other advantages of lidose technology are: (1) a good mass

and drug content uniformity, the volumetric filling of a liquid is

not influenced by density of the product; (2) lidose protects the

active ingredient against oxidation; and (3) capability to use hard

gelatin capsules for: liquid substances, low dosing substances so

as to obtain a uniform blend of sensitive substances, and slightly

soluble drugs to obtain dispersion.

OBJECTIVES:General Objective:

To determine the efficacy and safety of fenofibrates particularly

Fenogal (lidose technology) in dyslipidemic patients

Specific Objective:

1. To determine the efficacy of Fenogal in decreasing triglycer-

ides, total cholesterol, and LDL; and increasing HDL

2. To determine the safety of the lidose technology using clini-

cal parameters, biochemical profile and side effects

Significance of the Study:

Fenofibrates are mainly indicated in the treatment of hy-

pertriglyceridemia when diet and lifestyle changes are not suf-

ficient. Fibrates are known to lower total cholesterol, LDL, while

increasing HDL when statins are not tolerated.1

Mixed dyslipidemia is a common lipid disorder described

by the presence of an atherogenic lipoprotein phenotype due to

abnormalities in various atherogenic and anti-atherogenic lipo-

proteins. Fenofibrates are particularly useful in high residual risk

seen in statin trials which may be due to lipoprotein abnormali-

ties other than LDL. It exerts favorable effects on the atherogen-

ic lipid profile of mixed dyslipidemia and can effectively reduce

cardiovascular disease in patients with mixed dyslipidemia.1

The addition of fenofibrate to statins seems to be beneficial

in patients with acute coronary syndrome. According to Shah et.

al., statins decreased plasma fibrinogen significantly and the ad-

dition of fenofibrate further enhanced this reduction of the novel

risk factor fibrinogen.3

2

Methodology:

This was an open labeled study of Fenogal 160mg once

daily involving adult out-patients of cardiologists and internist

all over the Philippines who have hypertriglyceridemia, hyper-

cholesterolemia, or both, from August 2007 to May 2009. Pre-

vious medications for dyslipidemia (statins, fenofibrates, gemfi-

brozil, ezetemibe) were discontinued prior to administration of

Fenogal. Demographic data of patients were based upon OPD

charts. Assessment of lipid parameters (total cholesterol, trig-

lycerides, LDL, and HDL) and were taken at baseline, week 4,

and week twelve. Blood pressure, heart rate, and biological

markers (SGOT, SGPT, alkaline phosphatase, and FBS) were also

measured at same interval.

Statistical Analysis:

Continuous data such as age, weight, and height were de-

The most common medicines taken by patients before

entering the study were simvastatin, 19.60% followed by

atorvastatin, 3.47% and Lipanthyl, 2.07%. There were 3 pa-

tients (0.10%) who were already on Fenogal before the study

started, see Appendix A.

The total cholesterol decreased significantly as early as

week 4 of therapy with actual change of 28.12 mg/dl and per-

cent change from baseline of 9.91%. At week 12, the actual

mean decrease was 44.01 mg/dl with percent change from

baseline of 16.37%.

Table 1 Baseline Characteristics of Patients Included in the Study

CHARACTERISTICS Mean SDAge (Years) 52 11.60Weight (lbs.) 150.67 25.08Height (cms.) 161.43 8.42 No. %Gender: Male 1519 50.6 Female 1471 49.0 Not Indicated 10 0.3 Total 3000 100Type of Dyslipidemia: Hypercholesterolemia 370 12.3 Hypertriglyceridemia 1002 33.4 Both 1506 50.2 Not Indicated 122 4.1 Total 3000 100

scribed using mean and standard deviation. Categorical data

were presented in frequency and percent distribution. To de-

termine the significance of change in the different outcome

variables, paired t-test was applied to the data. A p-value ≤

0.05 was considered significant.

Results:

There were 3,000 patients included in this open labeled

study with a mean age of 52 ± 11.60 years. There were almost

equal number of males (50.6%) and females (49.0%). However,

there were 10 patients with gender not indicated. More than

half (50.2%) of the patients were with both hypercholester-

olemia and hypertriglyceridemia. Only 12.3% were with hyper-

cholesterolemia, 33.4% with hypertriglyceridemia, and majority

at 50.2% were with both, as shown in Table 1.

LDL likewise significantly decreased from baseline to

week 4 and week 12. The actual mean decrease at week 4

was 17.41 mg/dl with percent change of 8.15% while at week

12 the mean decrease was 29.86 mg/dl with percent change

of 15.91%.

HDL on the other hand increased significantly after 4

weeks and 12 weeks of treatment. The actual mean increase

was 4.27 mg/dl and percent increase from baseline of 15.64%.

At week 12, the actual increase was 6.80 mg/dl with percent

change from baseline of 23.51%.

3

Table 2 Assessment of Lipid Profile of Patients by Observation Periods

Observation Period Lipid Profile Mean SDTotal Cholesterol Baseline (n=2489) 232.45 64.12 Week 4 204.33 48.18 Difference: Actual 28.12 51.19 Percent from baseline 9.91 19.67 p-value 0.000* Baseline (n=2909 229.84 62.00 Week 12 185.83 41.75 Difference: Actual 44.01 56.33 Percent from baseline 16.31 20.88 p-value 0.000*LDL Baseline (n=2239) 140.47 51.11 Week 4 123.06 39.82 Difference: Actual 17.41 34.32 Percent from baseline 8.15 26.39 p-value 0.000* Baseline (n=2599) 139.01 51.91 Week 12 109.15 36.82 Difference: Actual 29.86 45.19 Percent from baseline 15.91 31.76 p-value 0.000*HDL Baseline (n=2217) 49.88 27.97 Week 4 54.16 26.81 Difference: Actual 4.27 19.26 Percent from baseline 15.64 42.60 p-value 0.000* Baseline (n=2580) 49.46 26.13 Week 12 56.26 25.32 Difference: Actual 6.80 22.18 Percent from baseline 23.51 48.38 p-value 0.000*

Triglycerides decreased significantly with actual mean of 60.30 mg/dl from baseline up to week 4 of therapy.

The percent decrease was 20.72%. At week 12, there was 90.61 mg/dl actual decrease and 33.15% change from

baseline. Table 2 shows the details of the effect of the treatment on lipid profile of the patients.

4

Triglyceride Baseline (n=2532) 234.98 98.11 Week 4 174.68 64.66 Difference: Actual 60.30 74.34 Percent from baseline 9.91 31.16 p-value 0.000* Baseline (n=2944) 235.27 97.84 Week 12 144.66 54.99 Difference: Actual 90.61 86.68 Percent from baseline 33.15 28.86 p-value 0.000*

A statistically significant favorable lipid lowering response based on NCEP-ATP III goals was achieved as early as 4 weeks of treatment and was sustained up to 12 weeks of treatment, see

table 3.

Table 3 Assesment of LIPID Response by NCEP-ATPIII Guideline by Observation Period

Lipid BaselineNo. No. p-value% %

Follow-up

Total Cholesterol Week 4 ≥ 200mg/dl 1806 72.6 1281 51.5 0.000* < 200mg/dl 683 27.4 1208 48.5 Total 2489 100 2489 100 Week 12 ≥ 200mg/dl 2061 70.8 944 32.5 0.000* < 200mg/dl 848 29.2 1965 67.5 Total 2909 100 2909 100

HDL Week 4 < 40mg/dl 852 38.4 531 24.0 0.000* ≥ 40mg/dl 1365 61.6 1686 76.0 Total 2217 100 2217 100 Week 12 < 40mg/dl 974 37.8 487 18.9 0.000* ≥ 40mg/dl 848 29.2 1965 81.1 Total 2580 100 2580 100

Triglyceride Week 4 ≥ 150mg/dl 2250 88.9 1706 67.4 0.000* < 150mg/dl 282 11.1 826 32.6 Total 2532 100 2532 100 Week 12 ≥ 150mg/dl 2625 89.2 1298 44.1 0.000* < 150mg/dl 319 10.8 1646 55.9 Total 2944 100 2944 100 LDL Week 4 ≥ 100mg/dl 1758 78.5 1458 65.1 0.000* < 100mg/dl 481 21.5 781 34.9 Total 2239 100 2239 100 Week 12 ≥ 100mg/dl or ↓ < 30% 2035 78.3 1264 48.6 0.000* < 100mg/dl or ↓ ≥ 30% 564 21.7 1335 51.4 Total 2599 100 2599 100

5

The systolic and diastolic blood pressures of patients decreased significantly from base-line to week 4 and week 12 of therapy. Heart rate likewise decreased significantly, as

shown in Table 4.

Table 4 Assessment of Vital Signs of Patients by Observation Period

Observation Period Lipid Profile Mean SDSystole Baseline (n=2624) 140 20.88 Week 4 129 13.51 Difference 10.67 13.66 p-value 0.000*

Baseline (n=2949) 138 20.89 Week 12 124 10.90 Difference 14.76 17.65 p-value 0.000*

Diastole Baseline (n=2624) 84 11.80 Week 4 82 8.09 Difference 5.65 9.59 p-value 0.000* Baseline (n=2949) 87 11.71 Week 12 79 7.22 Difference 7.95 11.05 p-value 0.000*

Heart Rate Baseline (n=2498) 79 9.87 Week 4 78 8.18 Difference 1.53 6.99 p-value 0.000* Baseline (n=2750) 79 9.57 Week 12 77 8.66 Difference 1.80 8.78 p-value 0.000*

6

There were no significant changes in SGOT and SGPT of patients. Alkaline phosphatase however showed significant increase in both 4th and 12th week observation periods.

FBS decreased significantly at week 4 and week 12 follow-up. Table 5 shows the results.

Table 5 Assessment of Laboratory Results by Observation Periods

Observation Period Lipid Profile Mean SDSGOT Baseline (n=1604) 32.05 17.78 Week 4 31.64 14.22 Difference 0.41 15.74 p-value 0.300 ns

Baseline (n=2949) 33.13 18.47 Week 12 32.69 15.33 Difference 0.44 19.33 p-value 0.326 nsSGPT Baseline (n=1902) 35.03 19.54 Week 4 34.93 19.26 Difference 0.10 19.12 p-value 0.817 ns Baseline (n=2239) 35.81 19.66 Week 12 35.85 25.15 Difference 0.04 26.63 p-value 0.945 ns

Alkaline phosphatase Baseline (n=943) 69.93 35.23 Week 4 73.47 39.59 Difference 3.54 22.37 p-value 0.000* Baseline (n=1061) 69.68 36.03 Week 12 71.85 38.22 Difference 2.18 27.13 p-value 0.009Fasting Blood Sugar Baseline (n=2076) 115.05 43.18 Week 4 104.94 24.92 Difference 10.12 27.89 p-value 0.000* Baseline (n=2398) 113.62 41.74 Week 12 100.27 21.93 Difference 13.34 34.82 p-value 0.000*

7

There were 34 patients who experience adverse events with 1.1% event rate. Most of the events were gastrointestinal related. Bloatedness was the most common. There

were also elevated laboratory results noted as shown in Table 6.

The compliance of patients was high, 95.3% as shown in Table 7

Table 6 Adverse Events Experienced by Patients

Adverse Events No. %Present 34 1.1Absent 2966 98.9 Total 3000 100 Specific Events Bloatedness 11 0.37Chest constriction 1 0.03Constipation 2 0.07Dyspepsia 1 0.03Elevated transaminase 2 0.07Elevated SGOT 2 0.07Elevated SGPT 3 0.10Elevated LDL 1 0.03Epigastric pain 2 0.07Epigastric discomfort 1 0.03Flatulence 5 0.17Abdominal fullness 1 0.03Nausea 1 0.03Gas pains 1 0.03Muscle pain 2 0.07Ringing of both ears 1 0.03

Table 7 Adverse Events Experienced by Patients Compliance No. %Yes 2860 95.3No 97 3.2Not Indicated 43 1.4 Total 3000 100

8

Discussion: Results of this study revealed that Fenogal (lidose tech-

nology) can significantly decrease triglycerides, LDL, and to-

tal cholesterol, while significantly increasing the HDL. Based

on the ATP III study, fibric acids were able to lower LDL by

5-20%, TG by 20-50%, increase HDL by 10-20%.7,8 Comparing

with the present study, similar changes in the lipid profile was

achieved, namely a decrease in TG by 90.61 mg/dL (33.15%),

an increase in HDL by 6.80 mg/dL (23.51%), and a decrease in

LDL by 29.86 mg/dL (15.91%). In addition we report a total

cholesterol decrease by 44.01 mg/dL (16.37%).

The 3rd Report of the National Cholesterol Education

Program (NCEP) Expert Panel on Detection, Evaluation, and

Treatment of High Blood Cholesterol in Adults (Adult Treat-

ment Panel III) Final Report state that the recommended lev-

els of plasma lipids are as follows: total cholesterol <200mg/

dL, HDL ≥40mg/dl, and triglycerides <150mg/dL. For LDL the

goal is based on the risk level: CHD and CHD risk equivalent

with a target of <100mg/dL, multiple (>2) risk factors with

a target of <130mg/dL and with 0-1 risk factor with a target

of <160mg/dL.7,8 In this study, these targets were achieved

as early as 4 weeks of treatment and was sustained up to

12 weeks of treatment with Fenogal. Total cholesterol de-

creased to a mean of 185.83mg/dL and mean triglyceride

level was 144.66mg/dL. Average LDL of 109.15mg/dL at 12

weeks was close to the recommended value of <100mg/dL as

well as mean HDL of 56.26mg/dL at 12 weeks was greater

than the prescribed value of ≥40mg/dL.

Grundy et. al., reported that when LDL lowering drug

therapy is employed in high-risk or moderately high-risk per-

sons, it is advised that intensity of therapy be sufficient to

achieve at least a 30-40% reduction in LDL-C levels.9 In our

study, a mean LDL level of 109.15mg/dL corresponding to a

15.91% reduction was achieved from baseline up to the 12

weeks of study. The results may not have reached the target

of the NCEP guidelines however the mean LDL was close to

the target level of 100mg/dL. In addition, one reason for

not achieving the goal may be that the subjects may rep-

resent a mixed dyslipidemic population such as in patients

with combined hyperlipidemia wherein only slight changes in

LDL cholesterol are observed with fibrates. Furthermore LDL

levels may rise with fibrate therapy in patients with hyper-

triglyceridemia.8

According to the National Nutrition and Health Survey

(NNHeS) study10 in 2003-2004, the average lipid levels and

prevalence of dyslipidemia among adult Filipinos >20 years

old are as follows: total cholesterol 184.4mg/dL (8.5%), LDL

119.4mg/dL (3.7%), HDL 41.1mg/dL (54.2%), and triglycerides

118.0mg/dL (20/6%).10 In the present study, it was noted

a higher mean baseline total cholesterol (232.45mg/dL), LDL

(140.47mg/dL), triglycerides (235.98mg/dL) and a somewhat

similar HDL level (49.88mg/dL). This may mean that the pop-

ulation in this study represents a high risk population while

the NNHes study included the normal average adult Filipino.

The study affirmed the safety of Fenogal in the treat-

ment of dyslipidemic patients as evidenced by no significant

changes in the SGOT and SGPT levels. The adverse event rate

was 1.1% and was mostly gastrointestinal related. Bloated-

ness was the most common complaint. This was consistent

with the NCEP ATP III guidelines which reported that fibrates

are generally well tolerated and the most common adverse

effects were gastrointestinal.7,8

Similarly, in a study done by Keating et.al., micronised

fenofibrate was associated with significantly greater im-

provements from baseline in TC, LDL-C, HDL-C and TG lev-

els than placebo in patients with type 2 diabetes mellitus

and metabolic syndrome as well as with significantly less

progression of coronary atherosclerosis than placebo. It was

generally well tolerated in clinical trials, and indicated that

gastrointestinal disorders are the most frequent adverse

events. Elevations in serum transaminase and creatine phos-

phokinase levels have been reported rarely with micronised

fenofibrate.11, 12

The improvement in the blood pressure, FBS and heart

rate may reflect the patients’ overall change in lifestyle

brought about by the physicians’ recommendation for such a

change. Likewise such improvements may represent an over-

all progress in the cardiovascular status of the patients as a

consequence of the correction of the lipid levels.

A number of trials 13,14,15,16 have been done world-

wide to determine the effectiveness of fibrates in the preven-

tion of cardiovascular disease. These include: Helsinki Heart

Study, Veterans Affairs High Density Lipoprotein Cholesterol

Intervention Trial (VA-HIT), Bezafibrate Infarct Prevention

(BIP) trial, and Fenofibrate Intervention and Event Lowering

in Diabetes (FIELD) trial which focused on patients with dia-

betes and dyslipidemia. However, results have indicated a

general trend that fibrates can reduce cardiovascular events.

9

Some studies have also suggested that fibrates may have

some significant non-cardiac side effects that other drugs do

not share. Fibrates may also be appropriate for use in pa-

tients at risk of acute pancreatitis due to high triglyceride

levels.

Based on the study done by Fiévet et.al.17, statin treat-

ment substantially reduces cardiovascular morbidity and

mortality. Statins lower LDL cholesterol (LDL-C), with limited

effects on other lipid parameters. Fibrates improve athero-

genic dyslipidemia characterized by high triglyceride and/

or low HDL cholesterol levels and elevated concentrations of

small dense LDL particles, with or without high LDL-C levels.

Fibrates decrease cardiovascular morbidity, especially in pa-

tients with the metabolic syndrome. The purpose of this re-

view is to provide a rationale for the combined use of statins

and fibrates in the management of patients with high resid-

ual cardiovascular risk related to atherogenic dyslipidemia

and persisting after single therapy. Reducing the residual

cardiovascular risk in patients treated with statins requires

addressing multiple lipid goals. In this context, future thera-

peutic interventions based on combination therapy, such as

statins and fibrates, appears particularly promising.

According to Shek et.al.14, practical recommendations

for clinicians who care for patients with refractory mixed

hyperlipidemia are needed. Combination therapy with a sta-

tin and fibrates offers significant therapeutic advantage for

the treatment of severe or refractory mixed hyperlipidemia.

Although such a combination does increase the risk of myo-

pathy, with an incidence of approximately 0.12%, this small

risk of myopathy rarely outweighs the established morbidity

and mortality benefits of achieving lipid goals. Nevertheless,

a higher incidence of myopathy has been reported with sta-

tin monotherapy. When monotherapy with a statin fails to

control mixed hyperlipidemia; combination therapy may be

considered. Niacin may be added before a fibrate is consid-

ered, as it appears to have less risk of myopathy. Statin-

fibrate combination therapy must be undertaken cautiously

and only after careful risk-benefit analysis. Patient counsel-

ing on the risks and warning signs of myopathy is extremely

important.18,19,20,21,22

The Adult Treatment Panel III of the National Cholesterol

Education Program issued an evidence-based set of guidelines

on cholesterol management. Since its release, there were 5

major clinical trials of statin therapy with clinical end points

have been published. Therapeutic lifestyle changes remain

an essential modality in clinical management. The trials

confirm the benefit of cholesterol-lowering therapy in high-

risk patients and support the ATP III treatment goal of LDL-C

<100mg/dL. It supported the inclusion of patients with diabe-

tes in the high-risk category and confirms the benefits of LDL-

lowering therapy in these patients. It further confirms that

older persons benefit from therapeutic lowering of LDL-C.

One of the major recommendations for modifications is that:

in high-risk persons, the recommended LDL-C goal is <100mg/

dL, but when risk is very high, an LDL-C goal of <70mg/dL is a

therapeutic option. This therapeutic option extends also to

patients at very high risk who have a baseline LDL-C <100mg/

dL. Moreover, when a high-risk patient has high triglycerides

or low HDL-C, consideration can be given to combining a fi-

brate or nicotinic acid with an LDL-lowering drug.7,8

Conclusion: The authors conclude that Fenogal (lidose technology)

can be safely and effectively included in the armamentarium

of cardiovascular medications. Profiles of patients who had

experienced rise in alkaline phosphatase needs further inves-

tigation. Even systolic and diastolic blood pressures, fasting

blood sugar, and heart rate were significantly lowered.

Recommendation:

The authors recommend the use of Fenogal (lidose

technology) to be included to optimize medical therapy in

patients with dyslipidemia.

Disclosure: The study was performed as part of the PMS (Post

Marketing Surveillance) required by the BFAD (Bureau of Food

and Drug) for Fenogal brand of Fenofibrate.

10

Bibliography:1. M Farnier. Update on the Clinical Utility of Fenofibrate in Mixed Dyslipidemias: Mechanisms of Action and Rational Prescrib-ing. Vasc Rsk and Hlt Mgmt 2008;4(5):991-10002. U De Faire, CG Ericson et al. Retardation of Coronary Atherosclerosis : The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and Other Angiographic Trials. Cardiovascular Drugs and Therapy 1997;11:257-2633. HD Shah, KH Parikh, MC Chag et al. Beneficial Effects of the Addition of Fenofibrate to Statin Therapy in Patients with Acute Coronary Syndrome After Percutaneous Coronary Interventions. Exp Clin Cardiol 2007;12(2):91-964. Arca M, Montali A, Pigna G, Antonini R, Antonini TM, Luigi P, Fraioli A, Mastrantoni M, Maddaloni M, Letizia C. Comparison of Ator-vastatin Versus Fenofibrate in Reaching Lipid Targets and Influencing Biomarkers and Endothelial Damage in Patients with Familial Combined Hyperlipidemia. Metabolism 2007 Nov;56(11):1534-415. Goa KL, Barradell LB, Plosker GL. Bezafibrate. An Update of its Pharmacology and use in the Management of Dyslipidemia. Drugs 1996 Nov;52(5):725-536. Spencer CM, Barradell LB. Gemfibrozil: A Reappraisal of its Pharmacological properties and Place in the Management of Dys-lipidaemia. Drugs 1996 Jun;51(6):982-10187. Grundy SM, Becker D, Clark L, et al. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Executive Summary. NIH Publication No. 01-3670. May 20018. Grundy SM, Becker D, Clark L, et al. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detec-tion, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. NIH Publication No. 02-5215. September 20029. Grundy SM, Cleeman JI, Merz CN, et al. Coordinating Committee of the National Cholesterol Education Program. Implica-tions of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004;110:227-23910. F Venandria, C Duante et al. Nutrition and Heath Status of Filipino Adults [Excerpts from the National Nutrition and Health Survey (NNHes)]: 2003-2004 for the Multisectoral Task Force on NNHes: 2003-2004. FNRI-DOST11. Keating GM, Ormrod D. Micronised Fenofibrate: an Updated Review of its Clinical Efficacy in the Management of Dyslipidaemia. Kardiol Pol. 2004 Jun;60(6):567-7712. Adkins JC, Faulds D. Micronised Fenofibrate: a Review of its Pharmacodynamic Properties and Clinical Efficacy in the Manage-ment of Dyslipidaemia. Drugs. 1997 Oct;54(4):615-33 13. SJ Robins, HB Rubins, et al. Insulin Resistance and cardiovascular events with low HDL cholesterol. The Veterans Affairs HDL Intervention Trial (VAHIT). Diabetes Care 2003;26(5):1513-151714. Shek A, a MJ. Statin-fibrate Combination Therapy. Circulation. 2002; 106:3369 15. FM Sacks. After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study: Implications for Fenofibrate. Am J Cardiol 2008;102(suppl):34L-40L 16. J Widimsky. The FIELD study Presented and Published. Unconvincing Results of Fenofibrates in Diabetic Patients. Vnitr Lek. 2006;52(1):80-417. Fiévet C, Staels B. Combination Therapy of Statins and Fibrates in the Management of Cardiovascular Risk. Am J Cardiovasc Drugs. 2009;9(6):401-9 18. Yang LP, Keating GM. Fenofibric Acid: In Combination Therapy in the Treatment of Mixed Dyslipidemia. Am J Cardiovasc Drugs. 2009;9(6):401-919. Derosa G, Cicero AE, Bertone G, Piccinni MN, Ciccarelli L, Roggeri DE. Comparison of Fluvastatin + Fenofibrate Combination Therapy and Fluvastatin Monotherapy in the Treatment of Combined Hyperlipidemia, Type 2 Diabetes Mellitus, and Coronary Heart Disease: A 12-month, Randomized, Double-blind, Controlled Trial. Clin Ther. 2004 Oct;26(10):1599-60720. Kłosiewicz-Latoszek L, Szostak WB, Grzybowska B, Białobrzeska-Paluszkiewicz J, Wiśniewska B, Stolarska I. Comparison of Combined Statin-Fibrate Treatment to Monotherapy in Patients with Mixed Hyperlipidemia. Kardiol Pol. 2004 Jun;60(6):567-7721. Vega GL, Ma PT, Cater NB, Filipchuk N, Meguro S, Garcia-Garcia AB, Grundy SM. Effects of Adding Fenofibrate (200 mg/day) to Simvastatin (10 mg/day) in Patients with Combined Hyperlipidemia and Metabolic Syndrome. Am J Cardiol. 2003 Apr 15;91(8):956-6022. Zambón D, Ros E, Rodriguez-Villar C, Laguna JC, Vázquez M, Sanllehy C, Casals E, Sol JM, Hernández G. Randomized Cross-over Study of Gemfibrozil Versus Lovastatin in Familial Combined Hyperlipidemia: Additive Effects of Combination Treatment on Lipid Regulation. Metabolism 1999 Jan;48(1):47-54

Medications No. %Afordel 1 0.03Atorvastatin 104 3.47

Cholestad 5 0.17Ciprofibrate 1 0.03Crestor 52 1.73

Ezetemibe 2 0.07Ezetrol 1 0.03Fenofibrate 49 1.63Fenoflex 8 0.27Fenogal 3 0.10Fibrafen 5 0.17Fibrate 3 0.10 Fluvastatin 3 0.10 Forcad 10 0.33Gemfibrozil 58 1.93Lescol 6 0.20Lipanthyl 62 2.07Lipigem 2 0.07Lipitor 58 1.93Lipway 5 0.17Lopid 18 0.60Niacin 9 0.30Nubrex 21 0.70Omacor 2 0.07

Orlistat 1 0.03Pravastatin 4 0.13 Reducel 14 0.47Rosuvastatin 31 1.03 Simvastatin 588 19.60Vamstat 1 0.03Vidastat 46 1.53

Vytorin 10 0.33Ximvast 1 0.03 Zocor 22 0.73Unrecalled 3 0.10None indicated 1877 62.56

Appendix A. Previous Medication of Patients for Dyslipidemia