Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function.

OBJECTIVES

To investigate the effect of enalapril, losartan, and surgical coronary revascularisation on endothelial function, and the role of the angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism.

DESIGN

Randomised, controlled, blinded end point study.

SETTING

University tertiary referral cardiac centre.

PATIENTS AND INTERVENTIONS

49 men awaiting coronary artery bypass grafting (CABG) were randomly assigned to treatment with losartan, enalapril, or control for two months before and three months after surgery.

MAIN OUTCOME MEASURES

Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined.

RESULTS

FMD was impaired at baseline (1.0-1.7%) and after five months had improved to 5.2% with enalapril (p = 0.015), 5.0% with losartan (p = 0.0004), and 3.0% with CABG alone (p = 0.05). Patients with the II genotype had lower baseline FMD than those with DI or DD (0.1% v 1.7%, p = 0.038) and after enalapril or losartan treatment had greater improvement in FMD (mean (SEM) 7.1 (1.1)%) than patients with DI (3.1 (1.3)%, p = 0.024) or DD genotype (3.1 (1.1)%, p = 0.02).

CONCLUSIONS

Enalapril and losartan, with surgical coronary revascularisation, significantly improve systemic endothelial function. Revascularisation alone produces a quantitatively smaller, but still significant, improvement. The ACE genotype significantly modulates this response. Patients with the II genotype have a more pronounced impairment in endothelial function at baseline and a greater improvement in response to treatment with these agents.