Posts Tagged ‘Journal of the American Medical Association’

Reporter: Aviva Lev-Ari, PhD, RN

Preliminary Communication | April 17, 2013

Effect of Shock Wave–Facilitated Intracoronary Cell Therapy on LVEF in Patients With Chronic Heart Failure The CELLWAVE Randomized Clinical Trial

Birgit Assmus, MD; Dirk H. Walter, MD; Florian H. Seeger, MD; David M. Leistner, MD; Julia Steiner; Ina Ziegler; Andreas Lutz, MD; Walaa Khaled, MD; Jens Klotsche, PhD; Torsten Tonn, MD; Stefanie Dimmeler, PhD; Andreas M. Zeiher, MD
JAMA. 2013;309(15):1622-1631. doi:10.1001/jama.2013.3527.


Importance  The modest effects of clinical studies using intracoronary administration of autologous bone marrow–derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs.

Objective  To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure.

Design, Setting, and Participants  The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011.

Interventions  Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs.

Main Outcomes and Measures  Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events.

Results  The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, −0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, −1.2% to 2.1%]) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58 [95% CI, 0.40-0.85]; P = .02).

Conclusions and Relevance  Among patients with postinfarction chronic heart failure, shock wave–facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials.

Trial Registration  clinicaltrials.gov Identifier: NCT00326989

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New Drug-Eluting Stent Works Well in STEMI

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 8/8/2013

Meta-analysis makes case for drug-eluting stents in STEMI

AUGUST 7, 2013 

New York, NY – Newer-generation drug-eluting stents, particularly the everolimus-eluting stent (Xience V, Abbot; Promus, Boston Scientific), significantly reduce the risk of target vessel revascularization (TVR) in patients with ST-segment-elevation MI (STEMI) without increasing the risk of adverse safety outcomes, including rates of stent thrombosis, when compared with bare-metal stents [1].

These are the principal findings of a new meta-analysis of 28 randomized, controlled clinical trials involving more than 34 000 patient-years of follow-up.

Published online August 6, 2013 in Circulation: Cardiovascular Interventions, the analysis showed that compared with the sirolimus-eluting stent (Cypher, Cordis), the paclitaxel-eluting stent (Taxus, Boston Scientific), and bare-metal stents, the use of an everolimus-eluting stent reduced the relative risk of stent thrombosis 62%, 61%, and 58%, respectively.

“I would make a strong argument to say that the current guidelines should change,” lead investigator Dr Sripal Bangalore (New York University School of Medicine) told heartwire. “The reduction in TVR is not surprising. We know that drug-eluting stents compared with bare-metal stents reduce TVR, but the biggest thing we were able show was that stent thrombosis is also reduced when compared with a bare-metal stent, as well as compared with first-generation drug-eluting stents.”

The current American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) clinical guidelines state that drug-eluting-stent implantation is a class IIa indication in STEMI patients. The recommendations are based on concerns about an increased risk of stent thrombosis with the drug-eluting stents compared with their bare-metal counterparts. Bangalore said concerns have also been raised about the risk of stent thrombosis beyond one year with the first-generation drug-eluting stents, a time point when dual antiplatelet therapy is stopped.

The newer-generation drug-eluting stents, however, have been shown in various studies to be as safe asbare-metal stents in the STEMI setting. For this reason, they conducted a meta-analysis of randomized, controlled trials comparing the sirolimus-, paclitaxel-, everolimus-, and zotarolimus-eluting stents against each other and against bare-metal stents.

When compared with bare-metal stents, the sirolimus-, paclitaxel-, and everolimus-eluting stent reduced the relative risk of TVR by 53%, 31%, and 57%, respectively. The sirolimus-eluting stent was significantly more effective than the paclitaxel-eluting stent at reducing TVR, as was the everolimus-eluting stent. Overall, there was a 67% probability that the Endeavor Resolute zotarolimus-eluting stent (Medtronic) had the lowest risk of TVR, although the data are based on just one trial with 281 patients, note the investigators.

Median rate of efficacy and definite/probable stent thrombosis

Stent type TVR rate (per 1000 patient-years of follow-up) Definite/probable stent thrombosis (per 1000 patient-years of follow-up)
Bare metal 64.00 16.60
Sirolimus 28.93 15.75
Paclitaxel 44.38 18.46
Everolimus 26.55 6.54
Zotarolimus 59.01 11.41
Zotarolimus (Resolute) 14.76 NA*


*For stent thrombosis, there were no available data on the Resolute stent

When compared with bare-metal stents, the everolimus-eluting stent reduced the risk of any stent thrombosis by 58%. The Xience stent was also associated with a statistically significant 62% and 61% reduction in the risk of stent thrombosis compared with the first-generation Cypher and Taxus stents.

Bangalore said that a previous patient-level analysis conducted by Dr Giuseppe De Luca (Ospedale Maggiore della Carità, Novara, Italy), reported by heartwire at that time, showed there was a significant 50% increase in the risk of late (more than one year) reinfarction with drug-eluting stents and an almost doubling of very late stent thrombosis with first-generation stents. In this newest meta-analysis, however, the researchers did not observe a similarly increased risk of very late stent thrombosis with the everolimus-eluting stent.

“Based on the totality of data, I would say that it’s time the guidelines make drug-eluting stents and especially the everolimus-eluting stent a class I indication in STEMI patients who can take dual antiplatelet therapy,” said Bangalore.


  1. Bangalore S, Amoroso N, Fusaro M, Kumar S, Feit F. Outcomes with various drug-eluting or bare-metal stents in patients with ST-segment elevation myocardial infarctionCirc Cardiovasc Interv 2013; DOI:10.1161/CIRCINTERVENTIONS.113.000415. Available at: http://circinterventions.ahajournals.org.


New Drug-Eluting Stent Works Well in STEMI

By Michael Smith, North American Correspondent, MedPage Today

Published: August 21, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

 Watch Video

 A new-generation biodegradable drug-eluting stent had a lower rate of major cardiac events than similar bare-metal devices, researchers reported.

In a randomized trial, patients with ST-segment elevation myocardial infarction (STEMI) needed fewer revascularization procedures and had a lower risk of a new heart attack in the target blood vessel, according to Stephan Windecker, MD, of Bern University Hospital in Bern, Switzerland, and colleagues.

On the other hand, rates of cardiac death were not significantly different, Windecker and colleagues reported in the Aug. 22/29 issue of the Journal of the American Medical Association.

Drug-eluting stents have been shown to reduce the need for repeat revascularization, compared with bare-metal stents, but at the cost of delayed healing, chronic inflammation, and late stent thrombosis, the researchers noted.

The long-term effects result from the persistence of the polymer, Windecker and colleagues noted — something that might be avoided by using a biodegradable polymer.

The biodegradable BioMatrix Flex stent, which delivers the immunosuppressant drug biolimus, was non-inferior in a 4-year trial to the sirolimus-eluting Cypher stent, which does not break down over time.

But it had not been tested against bare-metal stents. To help fill the gap, Windecker and colleagues studied 1-year outcomes in 1,161 STEMI patients randomly assigned to get either the biolimus-eluting biodegradable stent or a similar bare-metal device.

The primary endpoint of the trial was the 1-year rate of major adverse cardiac events — a composite of cardiac death, target vessel-related re-infarction, and ischemia-driven target-lesion revascularization.

Windecker and colleagues found that 24 patients (4.3%) with biodegradable stents had a major adverse cardiac event at 1 year, compared with 49 (8.7%) who were given the bare-metal devices (HR 0.49, 95% CI 0.30 to 0.80, P=0.004).

The difference was driven by a lower risk of two of the elements of the combined endpoint: target vessel-related reinfarction and ischemia-driven target-lesion revascularization. Specifically:

  • Three patients getting the biodegradable stent (0.5%) had a re-infarction related to the target vessel, compared with 15 (2.7%) of those with bare-metal devices (HR 0.20, 95% CI 0.06 to 0.69, P=0.01).
  • Nine patients (1.6%) with biodegradable stents and 32 (5.7%) with bare-metal devices needed target-lesion revascularization (HR 0.28, 95% CI 0.13 to 0.59, P<0.001).
  • Rates of cardiac death were numerically lower, but not significantly so, in the biodegradable stent patients — 16 deaths, or 2.9%, versus 20, or 3.5%.

Definite stent thrombosis occurred in five patients treated with the drug-eluting stents and 12 patients with bare-metal stents, but the difference did not reach significance.

The findings should be “reassuring” to both doctors and patients, Windecker said in a video released by the journal.

The study is “a well-done trial with convincing results regarding its primary end point,” commented Salvatore Cassese, MD, and Adnan Kastrati, MD, both of the Technische Universitat in Munich, Germany.

But, in an accompanying editorial, they argued that it still may not settle the question of long-term complications.

Despite “positive signals,” they wrote, the study has “neither the required sample size nor the sufficient length of follow-up to provide the definitive answer about the long-term safety” of the new biodegradable drug-eluting stents.

The researchers cautioned that the biodegradable drug-eluting stent is not yet approved in the U.S., although European authorities have given it the nod.

They also noted that the study, while demonstrating superiority on the overall endpoint, did not have sufficient statistical power to address the individual components definitively.

The study had support from the Swiss National Science Foundation and Biosensors Europe SA. Windecker reported financial links through his institution with Abbott, Boston Scientific, Biosensors, Biotronik, Cordis, Medtronic, and St. Jude Medical.

The editorial authors reported support from the European Commission. Kastrati reported holding a patent related to polymer-free sirolimus and probucol coating, as well as financial links with Abbott, Biosensors, Cordis, and Medtronic.

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