The Val-PREST Trial
The Val-PREST Trial
The following study was performed to evaluate the effects of chronic 6-month administration of the angiotensin I receptor antagonist valsartan on restenosis rate after stenting of type B2/C lesions in comparison to placebo. Despite encouraging results of the BENESTENT and STRESS trials, stenting of complex coronary lesions leads to an in-stent restenosis rate of up to 40%. Several attempts at systematic medical therapy (e.g., ACE inhibitors) have not improved these results. Because of the important role of angiotensin in endothelial function, the hypothesis that angiotensin I receptor antagonists after stent implantation lead to a reduction of the in-stent restenosis rate should be tested in a single-center trial. Two hundred and fifty patients with type B2/C coronary lesions were randomized in an open-label study with respect to age, gender, lesion type and indication of percutaneous coronary intervention to a chronic administration of 80 mg valsartan or placebo (beta-blocking agents and/or ACE inhibitors). In-stent restenosis rate according to quantitative coronary angiography (QCA) and need for reintervention as primary and secondary endpoints were analyzed after a repeat angiogram at 6 months in 99 patients with 80 mg valsartan and 101 patients with placebo. Chronic administration of 80 mg valsartan reduced the in-stent restenosis rate to 19.2% (n = 19/99) in comparison to placebo with an in-stent restenosis rate of 38.6% (n = 39/101) (p < 0.005). Reintervention rate was 28.7% (n = 29/101) in the placebo group and only 12.1% (n = 12) in the valsartan group (p < 0.005). QCA analysis of stented coronary segments disclosed no differences in reference vessel diameter (2.68 ± 0.26 mm in the valsartan group versus 2.71 ± 0.24 mm in the placebo group) but significant differences in stented vessel diameter (2.17 ± 0.27 mm in the valsartan group and 1.60 ± 0.20 mm in the placebo group) (p < 0.000001).
In the BENESTENT and STRESS trials, Ulrich Sigwart stated in 1996 that stenting seemed to be the mechanical solution of a biological problem that included pathological remodeling and intimal dissection after balloon angioplasty. Despite these first encouraging results, the restenosis rate after stenting is higher than expected in daily practice with a high frequency of stent implantation and more and more percutaneous coronary interventions in complex type B2/C lesions. According to several studies, real-world restenosis rates after stent implantation in all kinds of de novo stenoses (long lesions, chronic occlusions, etc.) and in restenoses after percutaneous transluminal coronary angioplasty (PTCA) seem to be between 35% and 50%.1-3 Although existing human trials with the ACE inhibitor cilazapril (the MERCATOR and MARCATOR trials) yielded no positive effects on restenosis rates,4,5 angiotensin II is one of the most important factors of endothelial function and intimal proliferation. This study examines the effect of the chronic administration of the angiotensin I receptor antagonist valsartan on a group of patients after stent implantation in type B2/C lesions.
The following study was performed to evaluate the effects of chronic 6-month administration of the angiotensin I receptor antagonist valsartan on restenosis rate after stenting of type B2/C lesions in comparison to placebo. Despite encouraging results of the BENESTENT and STRESS trials, stenting of complex coronary lesions leads to an in-stent restenosis rate of up to 40%. Several attempts at systematic medical therapy (e.g., ACE inhibitors) have not improved these results. Because of the important role of angiotensin in endothelial function, the hypothesis that angiotensin I receptor antagonists after stent implantation lead to a reduction of the in-stent restenosis rate should be tested in a single-center trial. Two hundred and fifty patients with type B2/C coronary lesions were randomized in an open-label study with respect to age, gender, lesion type and indication of percutaneous coronary intervention to a chronic administration of 80 mg valsartan or placebo (beta-blocking agents and/or ACE inhibitors). In-stent restenosis rate according to quantitative coronary angiography (QCA) and need for reintervention as primary and secondary endpoints were analyzed after a repeat angiogram at 6 months in 99 patients with 80 mg valsartan and 101 patients with placebo. Chronic administration of 80 mg valsartan reduced the in-stent restenosis rate to 19.2% (n = 19/99) in comparison to placebo with an in-stent restenosis rate of 38.6% (n = 39/101) (p < 0.005). Reintervention rate was 28.7% (n = 29/101) in the placebo group and only 12.1% (n = 12) in the valsartan group (p < 0.005). QCA analysis of stented coronary segments disclosed no differences in reference vessel diameter (2.68 ± 0.26 mm in the valsartan group versus 2.71 ± 0.24 mm in the placebo group) but significant differences in stented vessel diameter (2.17 ± 0.27 mm in the valsartan group and 1.60 ± 0.20 mm in the placebo group) (p < 0.000001).
In the BENESTENT and STRESS trials, Ulrich Sigwart stated in 1996 that stenting seemed to be the mechanical solution of a biological problem that included pathological remodeling and intimal dissection after balloon angioplasty. Despite these first encouraging results, the restenosis rate after stenting is higher than expected in daily practice with a high frequency of stent implantation and more and more percutaneous coronary interventions in complex type B2/C lesions. According to several studies, real-world restenosis rates after stent implantation in all kinds of de novo stenoses (long lesions, chronic occlusions, etc.) and in restenoses after percutaneous transluminal coronary angioplasty (PTCA) seem to be between 35% and 50%.1-3 Although existing human trials with the ACE inhibitor cilazapril (the MERCATOR and MARCATOR trials) yielded no positive effects on restenosis rates,4,5 angiotensin II is one of the most important factors of endothelial function and intimal proliferation. This study examines the effect of the chronic administration of the angiotensin I receptor antagonist valsartan on a group of patients after stent implantation in type B2/C lesions.
