Igino Proietti

Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS study)

OBJECTIVES This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.

Effect of Atorvastatin (80 mg) Initiated at the Time of Coronary Artery Stent Implantation on C-Reactive Protein and Six-Month Clinical Events

and Hall, 1991:467–471. 8. Strandberg TE, Vanhanen H, Tikkanen MJ. Associations between change in C-reactive protein and serum lipids during statin treatment. Ann Intern Med 2000;32:579–583. 9. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels. The Pravastatin Inflammation/CRP Evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001;286:64–70. 10. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS. Measurement of C-reactive protein for targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959 – 1965. 11. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:1296–1310. 12. Horne R. Compliance, adherence and concordance, In: Taylor K. Harding G, eds. Pharmacy Practice. London: Taylor and Francis, 2001:165–184. 13. Ryan AA. Medication compliance and older people: a review of the literature. Int J Nursing. Studies 1999;36:153–162.

Randomized Comparison of XiEnce-V and Multi-link VisioN Coronary Stents in the sAme muLtivessel Patient with Chronic kiDnEy diSease (RENAL-DES) Study

Background— Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the rate of target vessel revascularization in comparison with bare-metal stents (BMS) in patients with chronic kidney disease. However, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess. Methods and Results— Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease (estimated glomerular filtration rate <60 mL/min). The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months. In 215 patients, 512 coronary vessels were successfully treated with the randomly assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7% (95% confidence interval, 1.1%–5.6%) and 11.4% (95% confidence interval, 7.8% to 16%), respectively, P<0.001. For the multivariate analysis, independent predictors of the ischemia-driven target vessel revascularization were BMS implantation (odds ratio, 4.95; 95% confidence interval, 2.1–11.6; P<0.001) and vessel size (odds ratio, 0.32; 95% confidence interval, 0.1–0.7; P=0.006). Conclusions— This is the first randomized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design, in patients who have chronic kidney disease with multivessel coronary artery disease. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00818792.

Chest pain after coronary artery stent implantation.

A sizeable proportion of patients who undergo successful coronary artery stent implantation experiences chest pain immediately after the procedure and/or in the following months in the absence of in-stent restenosis. We investigated this phenomenon in 57 consecutive patients with stable angina who underwent successful stent implantation. Chest pain characteristics were assessed before stent implantation and during 6-month follow-up. All patients underwent coronary angiography within 6 months of the procedure 48 hours after exercise thallium-201 perfusion scintigraphy. Patients who did not exhibit in-stent restenosis underwent an ergonovine test at the end of routine coronary angiography. During follow-up, 15 patients complained of chest pain. Six of these patients exhibited scintigraphic evidence of myocardial ischemia and in-stent restenosis at angiography. In the remaining 9 patients, chest pain occurred in the absence of in-stent restenosis at angiography. In 8 of these patients intracoronary ergonovine administration reproduced their habitual pain, whereas it did not cause any pain in the 42 patients who were completely asymptomatic at follow-up and without in-stent restenosis. Ergonovine caused more intense vasoconstriction and nitroglycerin caused more intense vasodilation of the reference coronary diameter in patients with than in patients without ergonovine-induced pain (-17 +/- 3 vs -9 +/- 3%, p <0.001; 9 +/- 6 vs 5 +/- 4%, p <0.02, respectively). In conclusion, chest pain with features similar to habitual angina occurs in the absence of in-stent restenosis in 1/5 of patients after stent implantation and appears to be associated with more intense coronary vasoreactivity.

Long-term results of immunosuppressive oral prednisone after coronary angioplasty in non-diabetic patients with elevated C-reactive protein levels.

AIMS To present the long-term results of prednisone-treated patients enrolled in the IMPRESS studies. Such studies demonstrated the efficacy of a short course of immunosuppression with oral prednisone after percutaneous coronary intervention (PCI) with bare metal stent (BMS) implantation compared to BMS alone at one year. METHODS AND RESULTS Eighty-four non-diabetic patients with elevated C-reactive protein after PCI treated with BMS and prednisone, were followed clinically for a minimum of five years. Event-free survival was defined as freedom from death, myocardial infarction, and need for target vessel revascularisation. Event-free survival rate at a mean of 6.5 +/- 1.4 years was significantly better in prednisone-treated patients of the IMPRESS and IMPRESS-2/MVD respectively compared to their original control arms: 87.8 versus 47.6%, relative risk: 7.9; 95%CI: 2.6-24.1, p<0.0001, log-rank=13.06, p=0.0003; and 93 versus 60.5%, relative risk: 8.7; 95%CI: 2.3-32.7, p=0.0004, log-rank=13,18, p=0.0003, respectively. The event-free survival was 54.1% in controls and 90.5% in the prednisone group; relative risk: 8.1; 95%CI: 3.5-18.7, p<0.0001, log-rank= 26.33, p<0.0001. CONCLUSIONS The clinical benefits of oral treatment with prednisone after conventional PCI in non-diabetic patients with evidence of systemic inflammation after stenting are maintained at long-term follow-up, either in patients with single or multivessel coronary artery disease.

A comparison of coronary artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery: five year clinical follow up

Background: Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA). Objective: To establish whether those results are maintained at five year follow up. Methods: Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records. Main outcome measures: Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina. Results: Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p  =  0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p  =  0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p  =  0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p  =  0.46) or cerebrovascular accident (2% v 0%). Conclusions: In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.

Prediction of Cardiovascular Events by Inflammatory Markers in Patients Undergoing Carotid Stenting

OBJECTIVE To assess whether inflammatory markers predict atherosclerotic disease activity after carotid treatment in patients with severe carotid stenosis and nonsignificant coronary artery disease undergoing carotid stenting. PATIENTS AND METHODS From March 1, 2004, to September 30, 2005, a total of 55 consecutive patients (mean ± SD age, 69±8.3 years; 26 men) with severe carotid stenosis and nonsignificant coronary artery disease were treated with carotid stent implantation. Patients were followed up for a period of 5 years for the occurrence of cardiovascular events. RESULTS A significant correlation between quantitative analysis of debris entrapped in the filters and inflammatory markers was found. Moreover, the number of particles per filter, the total particles area, and the mean particle axis per filter were significantly higher in patients with clinical events at the follow-up compared with patients without events (87 vs 32, P=.006; 50,118.7 vs 17,782, P=.002; 33.9 vs 30.2, P=.03). At 5-year follow-up we recorded cardiovascular or neurologic events in 11 of the 55 patients (20%). Higher preprocedural levels of high-sensitivity C-reactive protein, interleukin 6 soluble receptor, and interleukin 6 were significantly associated with clinical events at follow-up (P<.001, P=.05, and P=.02, respectively). In particular high-sensitivity C-reactive protein measured at 24 and 48 hours after carotid stenting showed a significant correlation with clinical events (P=.001). Also preprocedural intracellular adhesion molecule 1 and circulating vascular cell adhesion molecule 1 blood concentrations were significantly correlated with a worse prognosis at follow-up (P=.04 and P=.03, respectively). CONCLUSION In patients with severe carotid stenosis and nonsignificant coronary artery disease, inflammation is associated with atherosclerotic disease activity and a worse prognosis. Interleukin 6, interleukin 6 soluble receptor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and high-sensitivity C-reactive protein levels at baseline and 24 and 48 hours after carotid stenting are predictive of neurologic and cardiovascular events at follow-up.

ORAl iMmunosuppressive therapy to prevent in-Stent rEstenosiS (RAMSES) cooperation: A patient-level meta-analysis of randomized trials

OBJECTIVE The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis. METHODS We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics. RESULTS Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24-0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21-0.67], P < 0.001) and late lumen loss (-0.39 mm [-0.67, -0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29-1.53], P = 0.34), death (0.82 [0.25-2.69], P = 0.71), MI (0.58 [0.24-1.39], P = 0.22) and stent thrombosis (0.43 [0.10-1.87], P = 0.26). CONCLUSION In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.

Left anterior descending and circumflex coronary artery spasm after right coronary artery stent implantation

A 47 year old woman with variant angina and recurrent ischaemic episodes, despite aggressive medical treatment, was referred to our attention. Coronary angiography showed a normal left coronary artery and significant …

One-Year Outcome From an All-Comers Population of Patients With ST-Segment Elevation Myocardial Infarction Treated With Biolimus-Eluting Stent With Biodegradable Polymer

To evaluate the performance of biolimus‐eluting stent (BES) in patients with ST‐elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in a real world clinical scenario.