Prediction of cardiovascular event risk reduction from lipid changes associated with high potency dyslipidemia therapy

Abstract

Background:

Epidemiological data suggests for every 1% reduction in LDL-C there is a corresponding 1–1.5% reduction in cardiovascular events (CVEs). Additionally, for every 2–3% increase in HDL-C there is a reduction in CVEs by 2–4% that is independent of LDL-C. With numerous treatment options for managing dyslipidemia, it is important to evaluate agents that result in the greatest reduction of CVEs.

Objective:

To compare current high-potency dyslipidemia pharmacotherapy with respect to changes in LDL-C and HDL-C and estimate risk reductions for CVEs.

Methods:

This study is an analysis of existing published studies for dyslipidemia products marketed in the US. Literature searches were conducted using Medline, International Pharmaceutical Abstracts, Embase, and CINAH to identify trials for niacin extended-release and lovastatin (NER/L); niacin extended-release and simvastatin (NER/S); rosuvastatin (R); and, ezetimibe/simvastatin (E/S) from database inception to 1 May 2009. Demographics and changes from baseline in LDL-C and HDL-C were abstracted and HDL-C to LDL-C change (%Δ-lipids) was created for each therapy. Using a previously validated model the percent reduction in CVEs was estimated for each treatment strategy.

Results:

Data for 177 treatment arms (120 unique reports), accounting for drug and dose were abstracted. The range in mean ± SD %Δ-lipids depending on drug dose was: E/S, 58 ± 6 to 67 ± 3; R, 51 ± 5 to 65 ± 5; NER/L, 33 ± 7 to 75 ± 7; and NER/S, 48 to 77 ± 4. Risk reductions were greatest for NER/statin combinations, with percent risk reductions greater than 77% for NER/S, 2000 mg/10 mg and 83% NER/S, 2000 mg/40 mg. Ignoring medication strengths, reductions in CVEs ranged from 58% for R, 60% for E/S, 61% for NER/L, and 72% for NER/S.

Limitations:

There are several potential limitations associated with this study including: publication bias, English only search, limited published studies with NER in combination with L or S, adherent populations, and aggregation of multiple populations.

Conclusion:

The results of the analysis suggest that greater risk reductions in CVEs occur with combination therapies, especially those including niacin extended-release (NER). Up to an 83% risk reduction was estimated for the highest doses of NER and simvastatin (NER/S).

Key words::

• Cardiovascular events
• Cholesterol
• Dyslipidemia
• Lipid-lowering therapy
• Lipids

Transparency

Declaration of funding

This research was supported by an unrestricted research grant from Abbott Laboratories Inc. (manufacturer of a niacin extended-release (ER) and niacin ER/simvastatin formulations). All authors have evaluated, edited and given approval for the submission of the manuscript: S.L.C. and D.C.M. conceived of, designed the study, conducted the literature search, evaluated articles, analyzed and interpreted the data, wrote the manuscript, critically revised the manuscript, and provided all administrative activities. The content of this paper represents the authors’ views, and was in no way censored by the sponsor. The sponsor was permitted to review the manuscript, but all final decisions regarding content remained the sole responsibility of the investigators.

Declaration of financial/other relationships

S.L.C. has disclosed that he has received sponsorship from Abbott Laboratories, Inc. with a grant to Strategic Therapeutics, LLC; grant/research finding from Abbott Laboratories; and has served as a consultant to Strategic Therapeutics, LLC. D.C.M. has disclosed that he has received sponsorship from Abbott Laboratories, Inc. with a grant to Strategic Therapeutics, Inc. and has served as a consultant to Strategic Therapeutics, LLC which has received funds from Abbott Laboratories, Inc. for this research.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is the recipient of research/grant funding from Onconova Therapeutics Inc. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgments

The authors would like to thank Abbott Laboratories Inc. for reviewing and commenting on a draft of the manuscript. No third-party editorial or medical writing support was provided to the authors.