Fenofibric acid: a new fibrate approved for use in combination with statin for the treatment of mixed dyslipidemia

Figures & data

Figure 1 The neutral or non-polar plasma lipids.

Figure 2 Apo B lipoprotein with neutral lipids contained in the core.

Reproduced with permission from Koschinsky ML, Marcovina SM. In: Ballantyne, CM, editor. Clinical Lipidology: A Companion to Braunwald’s Heart Disease. Philadelphia: Saunders Elsevier; 2009:130–143.¹³ Copyright © 2009 Elsevier.

Table 1 Optimal lipid goals in high risk patients.

	Male	Female
LDL	<100 mg/dL	<100 mg/dL
HDL	>40	>50
TG	<150	<150
Non-HDL	<130	<130

Notes: Consistent with published recommendations from the NCEP ATPIII, American Heart Association and American Diabetes Association.

Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; TG, triglycerides.

Figure 3 Increases in triglycerides associated with increases in CHD risk: a meta-analysis of 17 prospective studies.

Notes: For every increase in serum TG level of 89 mg/dL, the risk of CHD increases 32% in men and 76% in women. The 17 prospective studies reporting association between elevated TG and CV endpoints included 46,413 men with 2445 events (average follow-up 8.4 years) and 10,864 women with 439 CV events (average follow-up 11.4 years).
Abbreviations: CHD, coronary heart disease; CV, cardiovascular; TG, triglycerides.

Figure 4 Prevalence of dyslipidemias in men <60 years with angiographic evidence of coronary atherosclerosis. Drawn from data of Genest et al.²³

Notes: This figure reveals a variety of lipid/lipoprotein abnormalities in patients with premature coronary artery disease. Significantly elevated plasma LDL is not commonly seen.
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; Lp(a), lipoprotein a; TG, triglycerides.

Figure 5 The average RRR for CV events in the secondary population even in the most intensive statin studies is 30%. This leaves significant residual risk for recurrent events. Superko and King³² compared a variety of studies utilizing LDL lowering versus LDL lowering and HDL elevation. This latter combined approach resulted in projected RRR of 71% to 6% with a NNT of 9.6 overall and 3.4/year.

Abbreviations: CV, cardiovascular; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein a; NNT, number needed to treate; RRR, relative risk reduction; TG, triglycerides.

Figure 6 Residual CVD risk in patients treated with intensive statin therapy.

A closer look at 3 trials investigating intensive LDL-C lowering with statin therapy in patients with CHD revealed that residual CVD risk remains in these patients even after aggressive LDL cholesterol lowering therapy. All 3 trials compared LDL-C lowering to ∼100 mg/dL with more intensive LDL-C lowering to ∼70 mg/dL as a means of preventing major CVD events in patients with a history of CHD or acute coronary syndromes. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) study (N = 4162), pravastatin 40 mg reduced LDL-C to 95 mg/dL and atorvastatin 80 mg reduced LDL-C to 62 mg/dL in patients who had been hospitalized for an acute coronary syndrome. After 2 years, 22.4% of patients treated with intensive statin therapy (atorvastatin 80 mg/dL) suffered a major CVD event.⁴ In the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study (N = 8888), simvastatin 20 mg reduced LDL-C to 104 mg/dL and atorvastatin 80 mg reduced LDL-C to 81 mg/dL in patients with a history of acute myocardial infarction. After 4.8 years, 12.0% of patients experienced a major CVD event even after intensive LDL-C lowering with statin therapy (atorvastatin 80 mg).⁶ Finally, in the Treating to New Targets (TNT) study (N = 10,001), 10 mg atorvastatin reduced LDL-C to 101 mg/dL and 80 mg atorvastatin reduced LDL-C to 77 mg/dL in patients with stable CHD. After 4.9 years, a major CVD event occurred in 8.7% of patients receiving intensive statin therapy (80 mg atorvastatin).⁵

These 3 trials reveal that significant residual CVD risk remains in patients even after intensive statin treatment.

Abbreviations: CVD, cardiovascular disease; CHD, coronary heart disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Figure 7 Structure and metabolic pathway for fenofibrate and fenofibric acid (TriLipix) in humans.

KoschinskyMLMarcovinaSMBallantyneCMClinical Lipidology: A Companion to Braunwald’s Heart DiseasePhiladelphiaSaunders Elsevier2009130143

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