Effect of ACE inhibitors on angiographic restenosis after coronary stenting (PARIS): a randomised, double-blind, placebo-controlled trial - PARIS
PARIS was a randomized, single-center, double-blind, placebo-controlled trial designed to study whether the angiotensin-converting enzyme (ACE) inhibitor quinapril would reduce restenosis after coronary stenting in patients homozygous for the deletion allele of the ACE gene polymorphism (DD).
Compared to placebo, quinapril 40 mg/day would reduce angiographic late lumen loss after coronary stenting in patients with the DD genotype for the ACE gene.
Patients Screened: 345
Patients Enrolled: 91
Mean Follow Up: 6 months
Mean Patient Age: less than 75 years old
Mean Ejection Fraction: Mean EF 64%
Successful coronary stenting at the time of enrollment and homozygous for the D allele of the angiotensin-I converting enzyme gene polymorphism.
Age ≥75, women of childbearing potential, acute MI within 48 hours before stenting, systolic BP < 120 mmHg, need for ACE inhibitor or angiotensin II antagonist treatment, renal or hepatic impairment, history of bleeding, contraindication to aspirin or ticlopidine, or angioplasty of a saphenous vein graft.
Change in minimal luminal diameter at 6-month follow-up angiography.
Minimal luminal diameter at 6 months, loss index, percentage of diamter stenosis at 6 months, binary angiographic restenosis rate (≥50% at the stented site)
Patients were screened immediately after coronary stenting and underwent rapid genotype testing for the ACE gene polymorphism. Patients with the DD genotype were enrolled and randomly assigned to 40 mg/day of quinapril or placebo. Subjects were followed for 6 months and underwent follow-up angiography at 6 months.
Aspirin and ticlopidine
345 patients underwent rapid genotyping after coronary stenting, and 91 patients with the DD genotype were randomized to quinapril or placebo. Hypertension and hypercholesterolemia were more frequent in the control group (p=0.03), but other baseline clinical and angiographic characteristics were similarly distributed in both groups. 11 (24%) patients assigned to quinapril and 7 (16%) control patients had a clinical event (myocardial infarction or revascularization) at 6 months (p not reported).
87% of patients underwent follow-up angiography. On intention-to-treat analysis, the late loss in minimal luminal diameter (MLD) was significantly greater in patients treated with quinapril compared with placebo (1.21 mm vs. 0.79 mm, p=0.015). On per-protocol analysis of patients who underwent follow-up angiography, late loss remained significantly greater in patients treated with quinapril vs. placebo (p=0.018) and there was a trend toward a greater binary restenosis rate in patients treated with quinapril vs. placebo (37% vs. 24%, p=0.23).
Among patients with the DD genotype of the ACE gene, administration of the ACE-inhibitor quinapril after coronary stenting was associated with greater angiographic late loss of MLD at 6 months compared with placebo. Patients with the DD genotype have been shown to be at increased risk of restenosis after stent placement. In the angiographic substudy of the QUIET trial, the progression of disease in patients treated with quinapril was similar to placebo. The increased late loss associated with quinapril in this study may represent a differential response to this drug in patients with the DD genotype. Whether this finding has clinical significance is unclear.
Meurice T, Bauters C, Hermant X, et al. Effect of ACE inhibitors on angiographic restenosis after coronary stenting (PARIS): a randomised, double-blind, placebo-controlled trial. Lancet 2001;357:1321-24.
Keywords: Myocardial Infarction, Follow-Up Studies, Tetrahydroisoquinolines, Genotype, Hypercholesterolemia, Hypertension, Stents, Paris, Peptidyl-Dipeptidase A
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