Study Looks at Adding Corticosteroid Treatment to Bare-Metal Stenting

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A short course of oral prednisone on top of optimal medical therapy in carefully selected patients who receive bare-metal stents (BMS) reduces adverse events compared with BMS alone. Results of the CEREA-DES trial, which were published online March 14, 2013, ahead of print in the European Heart Journal, show equivalent results between the BMS-plus-prednisone approach and drug-eluting stents (DES).

Four-year results of the trial were remarkably unchanged from 1-year results initially presented in September 2009 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA.

Researchers led by Flavio Ribichini, MD, of the University of Verona (Verona, Italy), randomized 375 nondiabetic ischemic patients at 5 Italian hospitals to 3 treatment strategies:

• BMS alone (n = 125)
• BMS with oral prednisone (n = 125; 1 mg/kg for first 15 days; 0.5 mg/kg from day 16 to day 30; 0.25 mg/kg from day 31 to day 40)
• DES (n = 125, Taxus Liberte, Boston Scientific, Marlborough, MA; or Cypher Select, Cordis/Johnson & Johnson, New Brunswick, NJ)

All patients received aspirin and ticlopidine or clopidogrel after successful stent implantation for at least 1 month. DES patients received dual antiplatelet therapy for 6 months to 1 year.

Over 4 years, patients receiving prednisone showed a reduction in MACE compared with those receiving BMS alone (16% vs. 28%; P = 0.04). Prednisone patients also showed trends for lower non-TLR plus non-TVR (9.6% vs. 16.8%; P = 0.06) and TVR (13.6% vs. 23.2%; P = 0.08) compared with BMS patients. DES patients showed similar MACE and revascularization rates compared with BMS-alone patients at 4 years, with higher rates of possible very late stent thrombosis (3.2% vs. 0; P = 0.02).

Event-Free Survival Maintained from 1 to 4 Years

Patients receiving BMS alone showed lower rates of the primary endpoint, event-free survival at 1 year from cardiovascular death, MI, and recurrence of ischemia needing repeat TVR (80.8%) compared with the prednisone (88.0%) and DES groups (88.8%; P = 0.04 and 0.006, respectively).

On intention-to-treat analysis, this was also true at 4 years, with lower event-free survival in the BMS group (75.3%) compared with the prednisone (84.1%; HR 0.447; 95% CI 0.29-0.80; P = 0.007) and DES groups (80.6%; HR 0.519; 95% CI 0.29-0.93; P = 0.03). These results were maintained on per-protocol analysis (P = 0.003 for BMS vs. prednisone; P = 0.05 for BMS vs. DES).

There was only 1 major bleeding event in each group. At 4 years, dual antiplatelet therapy was still being used in 23.2% of DES patients, 4.8% of BMS patients (P < 0.001), and 3.2% of prednisone patients (P = 0.68 for BMS vs. prednisone).

No adverse events related to prednisone treatment were reported.

The clinical benefits of prednisone observed at 4 years “may suggest a beneficial effect of the immunosuppressive and/or anti-inflammatory cycle against atherosclerosis progression in the coronary vascular tree,” the authors write.

In addition, the lower need for repeat intervention in nontreated vessels (non-TLR and non-TVR) may suggest broader treatment benefits that “if proved by adequately conceived investigations, may benefit patients undergoing PCI irrespective of the type of stent implanted,” they add.

Dr. Ribichini and colleagues note that the current study adds to prior research demonstrate that prednisone helps protect against restenosis in complex patients with diffuse disease, long lesions, or bifurcations and that due to the low cost of the drug, “this strategy may help patients (and doctors) in situations of economic restrictions wherever the cost of DES is still an issue.”

An Option But Only for a Select Few

In a telephone interview with TCTMD, Ron Waksman, MD, of Washington Hospital Center (Washington, DC), noted that immunosuppressive therapy may be an option for patients who require stenting, but “it should be reserved for a very select group. The study provides good news that if you’re careful about selection of patients you can end up without any major side effects and relatively acceptable results.”

In terms of selection criteria, CEREA-DES excluded patients over age 80 who had diabetes, recent Q-wave MI, uncontrolled hypertension, gastric ulcer, severe renal failure, left main disease and contraindications to steroids or dual antiplatelet therapy.

Dr. Waksman noted that since the time of the study—roughly 5 to 6 years ago—DES and BMS technology have greatly improved. “What is driving this is primarily the cost of DES and the fact that we were worried more about the first generation of stents,” he said. “But I don’t think this is an alternative to DES today . . . except for patients who can’t tolerate DES.”

In terms of potential benefits in avoiding extended dual antiplatelet therapy with DES, Dr. Waksman noted that the field is currently moving toward shorter lengths of therapy. In addition, “there are other strategies for patients who cannot tolerate dual therapy like drug-coated balloons,” he said. “At the end of the day, [immunosuppressive therapy] is an inferior product to current-generation DES.”

 

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Source:
Ribichini F, Tomai F, Pesarini G, et al. Long-term clinical follow-up of the multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: Cortisone plus BMS or DES veRsus BMS alone to EliminAte Restenosis (CEREA-DES). Eur Heart J. 2013;Epub ahead of print.

 

 

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