Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound

doi:10.1016/j.ahj.2004.10.032

American Heart Journal

Volume 149, Issue 3, March 2005, Pages 520-526

https://doi.org/10.1016/j.ahj.2004.10.032 Get rights and content

Background

Restenosis after coronary stenting is mainly caused by intimal hyperplasia. Both experimental and clinical studies suggest that statins may be able to inhibit intimal hyperplasia and, therefore, in-stent restenosis (ISR), by mechanisms beyond lipid lowering.

Methods

In a 12-month study, we randomized 71 normocholesterolemic patients to 20 mg simvastatin or no treatment, 2 weeks before elective coronary stenting. Patients were evaluated by quantitative coronary angiography and intravascular ultrasound, immediately after the index procedure and at the 12-month catheterization.

Results

Binary ISR was present in 15% and in 18% of simvastatin-treated patients and controls, respectively (P = NS). Intimal hyperplasia did not differ significantly between the 2 groups (3.6 ± 1.8 vs 3.8 ± 2.3 mm³/mm, 34% ± 15% vs 35% ± 23% for simvastatin vs controls, P = NS). However, peristent plaque decreased with simvastatin but increased in controls (−4.0 ± 4.0 vs +1.6 ± 3.8 mm³/mm, −14% ± 10% vs +6% ± 12%, P < .05). The same behavior was shown by intermediate plaques at nonstented sites (−2.5 ± 3.0 vs +1.0 ± 3.0 mm³/mm, −10% ± 8% vs +9% ± 9%, P < .05). Major adverse events at 12 months were present in 11% and 24% of simvastatin-treated patients and controls, respectively (P = .20).

Conclusions

In normocholesterolemic patients undergoing coronary stenting, simvastatin does not prevent intimal hyperplasia or ISR, but it promotes atherosclerotic regression both at stented and at nonstented sites.

Section snippets

Patient population and study design

This was an open-label, randomized, single-center study in which simvastatin was compared with no treatment. Primary end points were angiographic ISR and ultrasound-assessed in-stent intimal hyperplasia. Secondary end points were ultrasound-assessed vessel wall changes and plaque progression/regression, and major adverse events.

Normocholesterolemic patients aged 18 to 75 years with angiographic findings of a significant de novo stenosis (>50% on quantitative coronary angiography [QCA]) on a

Results

Between January and June 2001, 85 patients who underwent coronary angiography at our Center satisfied the inclusion criteria; 72 of them agreed to be enrolled and underwent randomization and subsequent coronary stenting. Immediate angiographic success was achieved in all: however, 1 patient had myocardial infarction (as a result of subacute stent thrombosis) during the index hospitalization. Thus, the final study population was represented by 71 patients (36 simvastatin, 35 controls); the

Discussion

To our knowledge, this is the first randomized study in which the effect of simvastatin on ISR and intimal hyperplasia after coronary stenting has been investigated in normocholesterolemic patients.

The main findings of our study are (1) a similar incidence of angiographic ISR and intimal hyperplasia in simvastatin-treated patients and controls and (2) a significant atherosclerotic regression both at stented and nonstented sites with simvastatin.

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Clinical InvestigationSimvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound

Background

Methods

Results

Conclusions

Section snippets

Patient population and study design

Results

Discussion

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Clin. Biochem.

Am. J. Cardiol.

Am. J. Cardiol.

Pharmacol. Ther.

Am. Heart J.

A comparison of balloon-expandable–stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group

N. Engl. J. Med.

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. The Stent Restenosis Study Investigators

N. Engl. J. Med.

Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study

Circulation

Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery

N. Engl. J. Med.

One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial

Circulation

Mechanisms of plaque stabilization with statins

Am. J. Cardiol.

Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group

N. Engl. J. Med.

Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease

Circulation

Statin therapy is associated with reduced restenosis rates after coronary stent implantation in carriers of the Pl(A2) allele of the platelet glycoprotein IIIa gene

Eur. Heart J.

Clinical Investigation
Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound