IMPRESS-2 MVD: Immunosuppressive Therapy for the Prevention of Restenosis After Coronary Artery Sten
IMPRESS-2 MVD: Immunosuppressive Therapy for the Prevention of Restenosis After Coronary Artery Stent Implantation Study in Patients With Multivessel Disease
Presenter: Flavio Ribichini, MD, European Hospital (Rome, Italy)
Previous studies have shown that inflammation plays a key role in the development of restenosis and subsequent events. In particular, C-reactive protein (CRP) is considered a marker of inflammation (patients with CRP levels > 0.3 mg/dL are considered to be at high risk for future cardiovascular events). Therefore, it has been hypothesized that reducing systemic inflammation may subsequently lower this risk.
Although drug-eluting stents have shown impressive reductions in restenosis, their use is restricted by high costs and technical limitations (bifurcations, small vessels, and diffuse disease). To overcome such obstacles, orally administered immunosuppressive agents such as rapamycin have been proposed as alternatives to drug-eluting stents. Research also continues to identify the impact of systemic anti-inflammatory treatment with steroids as an alternative to stents for the prevention of restenosis. The rationale for the use of steroids is that they target inflammation as a mechanism of restenosis, are capable of obtaining a systemic effect with low toxicity, may simplify percutaneous coronary intervention (PCI) techniques, and reduce associated costs.
The Immunosuppressive Therapy for the Prevention of Restenosis After Coronary Artery Stent Implantation Study (IMPRESS) documented the safety and effectiveness of prednisone therapy and demonstrated a marked reduction of clinical events and angiographic restenosis compared with control. The trial enrolled 83 patients who underwent successful single-stent implantation with CRP levels > 0.5 mg/dL 72 hours after the procedure and randomized them to either a 45-day regimen of prednisone or control.
Study Design
Whereas the first IMPRESS trial evaluated prednisone therapy administered to patients who had elevated CRP levels following single-stent implantation, IMPRESS-2 MVD was a prospective controlled registry that assessed the safety and applicability of high-dose prednisone in patients with multivessel disease who underwent successful multiple-stent implantation and had elevated CRP levels following the procedure. Patients eligible for prednisone therapy included those with:
Patients who met the following criteria were excluded from receiving prednisone therapy:
Patients who met inclusion criteria and did not have any of the conditions specified in the exclusion criteria were treated with prednisone; patients assigned to the control group represented those patients who did not meet all criteria. Patients in the treatment arm underwent quantitative coronary angiography (QCA) at 8 months, whereas patients in the control arm only had clinical follow-up at 8 months; both groups underwent clinical follow-up at 12 months.
Results
A total of 95 consecutive patients who underwent multivessel PCI were randomized to either prednisone (no exclusion criteria and high CRP) (n = 43, 115 lesions) or to control (exclusion criteria or low CRP) (n = 52, 123 lesions). Baseline clinical characteristics were well balanced between the 2 groups, with the exception of a significantly higher incidence of diabetes in the control group and a slightly higher incidence of hypertension in the prednisone group (Table 1) -- findings that were in line with the enrollment criteria.
Table 1. Baseline Clinical Characteristics
*P = .04
P < .001
CRP = C-reactive protein; MI = myocardial infarction; PCI = percutaneous coronary intervention
In the prednisone group, 6 patients experienced side effects (14%). At follow-up, major adverse cardiac event rates and the rate of target vessel revascularization were significantly lower in the prednisone group than in the control group. In addition, there were no reported deaths or episodes of myocardial infarction in the treated group (Table 2). Late loss in patients who underwent QCA (91% follow-up) was 0.61 ± 0.35 mm, with a restenosis rate of 3.8%.
Table 2. Clinical Follow-up
MACE = major adverse cardiac events; MI = myocardial infarction
Conclusions
The conclusions reached by the investigators were:
This small study is almost certain to provoke a lot of controversy. Prolonged steroid treatment is not an innocuous alternative to drug-eluting stents, as may be seen by the relatively high rate (14%) of side effects in the prednisone group. I am not completely convinced that the results prove the benefit of this treatment. It would be more interesting to see a double-blind, randomized trial evaluating drug treatment vs placebo that would include the use of intravascular ultrasound to assess late loss at 6 months.
Reference
Previous studies have shown that inflammation plays a key role in the development of restenosis and subsequent events. In particular, C-reactive protein (CRP) is considered a marker of inflammation (patients with CRP levels > 0.3 mg/dL are considered to be at high risk for future cardiovascular events). Therefore, it has been hypothesized that reducing systemic inflammation may subsequently lower this risk.
Although drug-eluting stents have shown impressive reductions in restenosis, their use is restricted by high costs and technical limitations (bifurcations, small vessels, and diffuse disease). To overcome such obstacles, orally administered immunosuppressive agents such as rapamycin have been proposed as alternatives to drug-eluting stents. Research also continues to identify the impact of systemic anti-inflammatory treatment with steroids as an alternative to stents for the prevention of restenosis. The rationale for the use of steroids is that they target inflammation as a mechanism of restenosis, are capable of obtaining a systemic effect with low toxicity, may simplify percutaneous coronary intervention (PCI) techniques, and reduce associated costs.
The Immunosuppressive Therapy for the Prevention of Restenosis After Coronary Artery Stent Implantation Study (IMPRESS) documented the safety and effectiveness of prednisone therapy and demonstrated a marked reduction of clinical events and angiographic restenosis compared with control. The trial enrolled 83 patients who underwent successful single-stent implantation with CRP levels > 0.5 mg/dL 72 hours after the procedure and randomized them to either a 45-day regimen of prednisone or control.
Study Design
Whereas the first IMPRESS trial evaluated prednisone therapy administered to patients who had elevated CRP levels following single-stent implantation, IMPRESS-2 MVD was a prospective controlled registry that assessed the safety and applicability of high-dose prednisone in patients with multivessel disease who underwent successful multiple-stent implantation and had elevated CRP levels following the procedure. Patients eligible for prednisone therapy included those with:
Angina or documented ischemia
Multivessel disease treated successfully by PCI (eg, balloon, stents, atherectomy)
Any lesion type
Any CRP value before stenting
CRP > 0.3 mg/dL 48 hours after stenting (vs CRP > 0.5 mg/dL for 72 hours after stenting in IMPRESS)
Patients who met the following criteria were excluded from receiving prednisone therapy:
Myocardial infarction in the last 3 weeks
Active peptic disease
Uncontrolled severe hypertension
Diabetes
Patients who met inclusion criteria and did not have any of the conditions specified in the exclusion criteria were treated with prednisone; patients assigned to the control group represented those patients who did not meet all criteria. Patients in the treatment arm underwent quantitative coronary angiography (QCA) at 8 months, whereas patients in the control arm only had clinical follow-up at 8 months; both groups underwent clinical follow-up at 12 months.
Results
A total of 95 consecutive patients who underwent multivessel PCI were randomized to either prednisone (no exclusion criteria and high CRP) (n = 43, 115 lesions) or to control (exclusion criteria or low CRP) (n = 52, 123 lesions). Baseline clinical characteristics were well balanced between the 2 groups, with the exception of a significantly higher incidence of diabetes in the control group and a slightly higher incidence of hypertension in the prednisone group (Table 1) -- findings that were in line with the enrollment criteria.
Table 1. Baseline Clinical Characteristics
| Characteristic | Prednisone (n = 43) | Control (n = 52) |
|---|---|---|
| Age (yrs) | 61 | 63 |
| Female (%) | 16 | 15 |
| Dyslipidemia (%) | 70 | 62 |
| Hypertension (%)* | 84 | 65 |
| Diabetes (%) | 0 | 37 |
| Unstable angina (%) | 28 | 19 |
| Previous MI (%) | 54 | 48 |
| CRP prior to PCI | 4.4 ± 7.4 | 6.4 ± 11.5 |
| CRP post PCI | 15.5 ± 18.6 | 22.6 ± 33.4 |
| Lesions per patient | 2.7 | 2.4 |
*P = .04
P < .001
CRP = C-reactive protein; MI = myocardial infarction; PCI = percutaneous coronary intervention
In the prednisone group, 6 patients experienced side effects (14%). At follow-up, major adverse cardiac event rates and the rate of target vessel revascularization were significantly lower in the prednisone group than in the control group. In addition, there were no reported deaths or episodes of myocardial infarction in the treated group (Table 2). Late loss in patients who underwent QCA (91% follow-up) was 0.61 ± 0.35 mm, with a restenosis rate of 3.8%.
Table 2. Clinical Follow-up
| Endpoint | Prednisone (n = 43) | Control (n = 52) | P Value |
|---|---|---|---|
| MACE (%) | 4.7 | 34.6 | .0004 |
| Death (%) | 0 | 5.8 | NS |
| MI (%) | 0 | 3.8 | NS |
| Target vessel revascularization (%) | 7 | 27 | .03 |
| Recurrence of angina (%) | 4.7 | 25 | .01 |
The conclusions reached by the investigators were:
In patients with diffuse multivessel disease and contraindications to steroid therapy and drug-eluting stents or coronary bypass surgery, conventional PCI should be the preferred treatment.
With the exception of diabetic patients and those with contraindications to steroid treatment, over 60% of patients are candidates for steroid treatment.
Oral prednisone may represent a convenient alternative to drug-eluting stents.
This small study is almost certain to provoke a lot of controversy. Prolonged steroid treatment is not an innocuous alternative to drug-eluting stents, as may be seen by the relatively high rate (14%) of side effects in the prednisone group. I am not completely convinced that the results prove the benefit of this treatment. It would be more interesting to see a double-blind, randomized trial evaluating drug treatment vs placebo that would include the use of intravascular ultrasound to assess late loss at 6 months.
Reference
Versaci F, Gaspardone A, Tomai F, et al. Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study). J Am Coll Cardiol. 2002;40:1935-1942.
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