TY - JOUR
T1 - Pitavastatin 4 mg Provides Significantly Greater Reduction in Remnant Lipoprotein Cholesterol Compared with Pravastatin 40 mg
T2 - Results from the Short-term Phase IV PREVAIL US Trial in Patients with Primary Hyperlipidemia or Mixed Dyslipidemia
AU - Miller, P. Elliott
AU - Martin, Seth S.
AU - Joshi, Parag H.
AU - Jones, Steven R.
AU - Massaro, Joseph M.
AU - D'Agostino, Ralph B.
AU - Sponseller, Craig A.
AU - Toth, Peter P.
N1 - Funding Information:
Funding for this study and its publication was provided by Kowa Pharmaceuticals America, Inc. The study sponsors were involved in the study design, collection, analysis, and interpretation of data; writing of the manuscript; and the decision to submit the manuscript for publication.
Publisher Copyright:
© 2016 Elsevier HS Journals, Inc. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Purpose Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C). Methods From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA. Findings Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group. Implications Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier: NCT01256476.
AB - Purpose Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C). Methods From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA. Findings Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group. Implications Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier: NCT01256476.
KW - Key words hyperlipidemia
KW - mixed dyslipidemia
KW - pitavastatin
KW - pravastatin
KW - remnant lipoprotein cholesterol
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U2 - 10.1016/j.clinthera.2016.02.001
DO - 10.1016/j.clinthera.2016.02.001
M3 - Article
C2 - 26922296
AN - SCOPUS:84960798659
SN - 0149-2918
VL - 38
SP - 603
EP - 609
JO - Clinical therapeutics
JF - Clinical therapeutics
IS - 3
ER -