A Medical Device Daily

At theEuropean Society of Cardiology (ESC)/
World Congress of Cardiology
(WCC; Sophia, Antipolis, France) annual meeting being held in Barcelona, Spain, researchers on Sunday issued reports indicating that drug-eluting stent (DES) devices may increase the risk of potentially fatal blood clots.

Up to 6 million patients worldwide have received DES devices since they were first launched in 2002, creating a $5-billion-a-year business for market leaders Boston Scientific (Natick, Massachusetts) and Johnson & Johnson (J&J; New Brunswick, New Jersey).

A meta analysis of results from past clinical trials of first-generation, DES devices presented at the meeting showed that DES-implasnted patients had a greater risk of heart attack or death than patients implanted with a bare metal stent. The increased relative risk was greatest for J&J's Cypher stent, at a statistically significant 38%, said Edoardo Camenzind, MD, of University Hospital (Geneva, Switzerland).

For Boston Scientific's Taxus stent the increased risk was 16%, a figure not meeting statistical significance.

The actual risk of death or heart attack was still low in both groups, at 6.3% for patients given Cypher and 2.6% for Taxus. But because DES devices are so widely used, thousands of patients could be affected.

Salim Yusuf, MD, of McMaster University (Hamilton, Ontario), said the findings were disconcerting. “Now that we are having this concern, I would urge limited use,” he said.

“As clinicians we seem to have lost our clinical judgment, let alone our ability to view data and evidence,” Yusuf added. “We therefore need a thoughtful and selective approach to PCI, complementing full medical therapy . . . The whole field of angioplasty has been led astray by a preoccupation with restenosis, for which study after study has shown has no prognostic value.

“We're chasing problems that are iatrogenic that naturally would not exist in people. We've had a perverse financial incentive on the practice of cardiology. It is time to stop and reevaluate.”

Drug coating has proved hugely popular because it prevents arterial scarring after a stent is implanted, which may cause arteries to narrow again in a process known as restenosis. However, the drug coating may delay healing around the stent, creating a risk of clots forming, which can trigger a heart attack, the researchers suggested.

The real worry is what happens after a year or more, with evidence growing that the risk of late stent thrombosis continues long after DES placement.

The latest research follows an earlier Swiss study that found the rate of heart attacks and deaths was more than three times higher in patients with DES devices who stopped taking blood-thinning drugs than those who had bare-metal stents.

Denis Donohue, vice president of clinical and regulatory affairs at J&J's Cordis (Miami Lakes, Florida) unit, told Reuters that late stent thrombosis was an issue but there was not a clear safety signal. He said the company's data showed long-term mortality rates of 6.5% for patients with a Cypher stent against 5.1% for bare metal stents, not a statistically significant difference.

J&J submitted its latest data to the FDA last week, Donohue said.

Alain Nordmann, MD, of University Hospital (Basel, Switzerland), renewed the call for a fresh look at DES, but one without industry involvement. He pointed out that obtaining raw data on mortality from the stent manufacturers has been “extremely difficult,” highlighting the need for non-company-sponsored, large randomized clinical trials with ample follow-up.

At the very least, said Yusuf, large registries should be mandated to track adverse DES events. But Yusuf also made a plea to the major cardiovascular organizations to revisit not only DES use but also the role of PCI in the treatment of stable, non-drug-refractory angina. He added that PCI and DES use play a key role in the treatment of unstable angina and acute coronary syndrome — it is as a treatment for stable angina to treat non-life-threatening restenosis that Yusuf singles out as a “myth” and a “man-made disease.”

As for the meta-analyses, Yusuf said: “These new studies raise concern. I do not believe these trials are convincing, but they are disconcerting given that we have no data that this procedure is useful. There is a significant excess in non-cardiac deaths, and we need to find out if this is real.”

Camenzind, for his part, stopped short of denying a role for DES devices, insisting that his misgivings apply only to the two first-generation drug-eluting stents. “We need stents that can control restenosis, that don't totally abolish the healing process but that are able to control it.”

In other ESC meeting news:

According to data presented at the meeting, long-term treatment with cardiac resynchronization therapy (CRT) or CRT with an implantable cardioverter defibrillator (CRT-D) is a cost-effective way to improve survival in patients with heart failure. Further analysis of data from the CARE-HF study, which demonstrates that CRT reduces mortality in heart failure patients, was also presented at ESC.

“The CARE-HF study provides conclusive evidence that, for patients with moderate or severe heart failure, CRT is a treatment that both improves symptoms and reduces mortality, a finding that is further supported by a meta-analysis of reported studies,” said Professor John Cleland, chairman of the CARE-HF steering committee and head of the Department of Cardiology, Castle Hill Hospital (Kingston-upon-Hill, UK). “An analysis of cost-effectiveness, using data from both the CARE-HF and COMPANION studies, shows that both CRT and CRT-D are highly cost-effective in patients with moderate or severe heart failure.”

The results demonstrate that the incremental cost-effectiveness is EUR 7,614 ($9,798) for CRT and EUR 18,199 ($23,419) for CRT-D when compared with optimal medical therapy per quality adjusted life year (QALY), substantially lower than the threshold of EUR 44,542 ($57,305) per QALY estimate, widely considered as acceptable value for cost effectiveness.

CARE-HF is a multi-center, international, randomized trial supported by Medtronic (Minneapolis), to evaluate long-term effects of CRT on mortality and morbidity among patients with moderate and severe heart failure. A total of 813 patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony were randomly assigned to pharmacology therapy alone or with the addition of CRT. Trial results demonstrated a 36% reduction in all cause mortality and 52% reduction in heart failure hospitalizations.

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