预测高强度降脂治疗引起的血脂变化对心血管事件风险的降低作用。

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

机构信息

School of Pharmacy, University of Colorado, 258 Leland Creek Circle, Box 1941, Winter Park, CO 80482-1941, USA.

出版信息

Curr Med Res Opin. 2010 Feb;26(2):365-75. doi: 10.1185/03007990903484802.

DOI:10.1185/03007990903484802

PMID:19995326

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 (%Delta-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 %Delta-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).

摘要

背景

流行病学数据表明，LDL-C 每降低 1%，心血管事件（CVE）相应降低 1-1.5%。此外，HDL-C 每增加 2-3%，CVE 就会降低 2-4%，且独立于 LDL-C。由于有多种治疗血脂异常的方法，因此评估能最大程度降低 CVE 的药物非常重要。

目的

比较目前高活性血脂异常药物治疗在 LDL-C 和 HDL-C 变化方面的差异，并估算 CVE 的风险降低情况。

方法

本研究对美国上市的血脂异常药物进行了现有已发表研究的分析。通过 Medline、国际药学文摘、Embase 和 CINAH 进行文献检索，以确定烟酸缓释剂和洛伐他汀（NER/L）；烟酸缓释剂和辛伐他汀（NER/S）；瑞舒伐他汀（R）；依折麦布/辛伐他汀（E/S）的临床试验。从数据库建立到 2009 年 5 月 1 日，检索文献以确定这些药物的临床试验。提取人口统计学数据和 LDL-C 和 HDL-C 的基线变化，并为每种治疗方法创建 HDL-C 与 LDL-C 的变化（%Delta-lipids）。使用先前验证的模型估算每种治疗策略的 CVE 降低百分比。

结果

共提取了 177 个治疗臂（120 个独特报告）的数据，涵盖了药物和剂量。根据药物剂量，%Delta-lipids 的平均值±SD 范围为：E/S，58±6%至 67±3%；R，51±5%至 65±5%；NER/L，33±7%至 75±7%；NER/S，48%至 77±4%。NER/他汀类药物联合治疗的风险降低最大，NER/S 2000mg/10mg 和 83%NER/S 2000mg/40mg 的风险降低超过 77%。忽略药物强度，R 的 CVE 降低率为 58%，E/S 为 60%，NER/L 为 61%，NER/S 为 72%。