Long-term safety and efficacy of fenofibrate/pravastatin combination therapy in high risk patients with mixed hyperlipidemia not controlled by pravastatin monotherapy

Abstract

Objective:

To assess the long-term safety and efficacy of a fenofibrate/pravastatin 160/40 mg fixed-dose combination in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.

Study design and methods:

After an 8-week pravastatin 40 mg and diet run-in period, high-risk patients (n = 248) with low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and triglycerides (TG) ≥ 150 and ≤400 mg/dL, were randomized to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy for 12 weeks, followed by an open-label, 52-week safety phase on the combination therapy.

Results:

Of the 224 patients who continued after the double-blind phase, 211 completed the one-year safety period. Overall, fenofibrate/pravastatin combination therapy was well tolerated during this extension study. Only three patients had an elevation of ALAT > 3 times the upper limit of normal and one patient a CPK elevation ≥5, but <10 times the upper limit of normal. At week 64, and by comparison to baseline levels on pravastatin 40 mg, the fenofibrate/pravastatin combination therapy significantly reduced non-high-density lipoprotein (non-HDL) cholesterol by 16.3%, LDL-C by 12.2%, TG by 31.6%, apolipoprotein B by 11.0% and increased HDL-cholesterol and apolipoprotein A1 respectively by 4.8 and 9.6% (p < 0.0001 for all the variables). A limitation of this trial is that the study was not powered to assess clinical events.

Conclusions:

Long-term co-administration of fenofibrate/pravastatin 160/40 mg in a single capsule was well tolerated and produced complementary benefits on the overall lipid profile of high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg.

Key words::

• Combination therapy
• Fenofibrate
• High-risk patients
• Pravastatin

Transparency

Declaration of funding

This study was financially supported by Laboratoires SMB SA, Brussels, Belgium.

Declaration of financial/other relationships

M.F. has received grant/research support and speaker’s honoraria from and served as a consultant and advisor for Abbott, Astra-Zeneca, Genzyme, Kowa, Lilly, Merck and Co, Merck-Schering-Plough, Novartis, Pfizer, Recordati, Roche, Sanofi-Aventis, SMB and Takeda. J.D. has received grant/research support and speaker’s honoraria from and served as a consultant and advisor for Astra-Zeneca, GSK, Lilly, Merck and Co, Merck-Schering-Plough, Pfizer, Sandoz, Sanofi-Aventis, SMB and Solvay. L.B. has received speaker’s honoraria from Merck and Co, Servier, Merck-Schering-Plough, Sanofi Aventis and Solvay.

CMRO peer reviewers have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors gratefully acknowledge the investigators who participated in this study.

In France: Philippe Marmor, Brigitte Flamand Lam, Olivier Decloux, Daniel Widmaier, Michel Drugeon, Philippe Cabourdin, Gilles Bindler, Michel Farnier, Jean Ferrières, Joëlle Fourcade, Patrick Garnier, Michel Krempf, Yassine Zaïr, Gérard Lasfargues, Pierre Lecomte, Bruno Passerat, Francis Philippe, Denis Smila, Albert Serrero, Guy Barberet, Thierry Dibetta, Gérald Luc, Jean-Michel Lecerf, Michel Weingrod, Jean-Paul Lacoste, Jean-Marc Sigogneau, Yahya Bouras, Christine Semon, Mathieu Marachli, Patrick Hassler, Jacques Bonnet, Bertrand Paviot, Vincent Richeboeuf, Claude Le Devehat, Michel Vimeux, Gérard Slama.

In Belgium: André Scheen, Philippe Ernest, Michèle Letiexhe, Jean Ducobu, Fabienne Lienart, Martine Marchal, Luc Van Gaal, Dominique Ballaux, Danny Schoors, Samir Khousam, André Nemery.

In Poland: Jarosław Krol, Agnieszka Raczkowska-Moszczenska, Michał Moszczenski, Bożena Klimkiewicz, Maciej Zarebinski, Tomasz Niemirka, Piotr Fratczak, Stanisław Bartus, Paweł Turek, Leszek Bryniarski, Artur Klecha, Jacek Dragan, Piotr Wilkolek, Marek Rodzaj, Jarosław Wasilewski, Agnieszka Mawlichanow-Kaczmarek, Włodzimierz Nowakowski.

The authors also thank to co-investigators, study coordinators, and patients who took part in this study.