心脏移植后降胆固醇治疗：一项为期12个月的随机试验。

Cholesterol-lowering therapy after heart transplantation: a 12-month randomized trial.

作者信息

Pflugfelder P W, Huff M, Oskalns R, Rudas L, Kostuk W J

机构信息

Department of Medicine, University Hospital, University of Western Ontario, London, Canada.

出版信息

J Heart Lung Transplant. 1995 Jul-Aug;14(4):613-22.

PMID:7578166

Abstract

BACKGROUND

Hypercholesterolemia, a common problem after heart transplantation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare the efficacy of gemfibrozil, simvastatin, and cholestyramine for cholesterol lowering in heart transplant recipients.

METHODS

In this prospective 1-year study, 48 heart transplant recipients with moderate hypercholesterolemia were randomized to therapy with gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was performed at baseline and after 3, 6, and 12 months of treatment.

RESULTS

Total cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%, respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained reduction in total cholesterol (25%) and low-density lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at the end of 1 year with simvastatin but not with the other treatments. Serum triglyceride levels were reduced significantly by treatment with gemfibrozil (up to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and gemfibrozil; however, this effect did not persist to 12 months. However, the ratio of low-density lipoprotein/high-density lipoprotein was favorably affected by simvastatin, with a 38% reduction by 12 months (p < 0.0001) but not by the other treatments. Over the course of 1 year, 14 patients dropped out of the study: four from the gemfibrozil arm and ten from the cholestyramine arm. Gastrointestinal intolerance was the most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No biochemical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels.

CONCLUSIONS

Of the three therapies studied, simvastatin was found to be the most efficacious and well tolerated for cholesterol lowering in patients after heart transplantation.

摘要

背景

高胆固醇血症是心脏移植术后常见问题，可能在同种异体冠状动脉疾病的发生和发展中起重要作用。本研究旨在比较吉非贝齐、辛伐他汀和考来烯胺在心脏移植受者中降低胆固醇的疗效。

方法

在这项为期1年的前瞻性研究中，48例中度高胆固醇血症的心脏移植受者被随机分为三组，分别接受以下治疗：吉非贝齐600毫克，每日两次（n = 17）；辛伐他汀10毫克，每日一次（n = 13）；考来烯胺4克，每日两次（n = 18）。在基线以及治疗3、6和12个月后进行详细的脂蛋白分析。

结果

辛伐他汀治疗3个月后，总胆固醇和低密度脂蛋白胆固醇分别降低了19%和29%（p < 0.0001），1年后总胆固醇持续降低25%，低密度脂蛋白胆固醇降低39%。吉非贝齐和考来烯胺治疗未使胆固醇水平降低。辛伐他汀治疗1年后载脂蛋白B水平降低29%，而其他治疗则未降低。吉非贝齐治疗可使血清甘油三酯水平显著降低（高达36%，p < 0.01），而其他治疗则无此效果。辛伐他汀和吉非贝齐治疗的患者高密度脂蛋白胆固醇最初有所升高；然而，这种效果在12个月时未持续。不过，辛伐他汀对低密度脂蛋白/高密度脂蛋白比值有有利影响，12个月时降低了38%（p < 0.0001），而其他治疗则无此效果。在1年的研究过程中，14例患者退出研究：吉非贝齐组4例，考来烯胺组10例。胃肠道不耐受是研究终止的最常见原因（14例中的8例）。辛伐他汀治疗组的所有患者均完成了12个月的治疗。任何治疗均未导致生化异常，且任何治疗均未引起环孢素血药浓度的显著改变。