Medtronic Responds to SORT-OUT III Stent Study -- Angioplasty.Org

Medtronic Responds to SORT-OUT III Stent Study
Flaws in Danish Study Comparing Endeavor® and Cypher® Drug-Eluting Stents Limit Relevance of Findings

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Medtronic, Inc.

March 15, 2010 -- Atlanta, GA -- Medtronic, Inc. (NYSE: MDT), responded today to the questionable findings of SORT-OUT III, a Danish study comparing the Endeavor and Cypher drug-eluting stents.

The company’s criticisms cover the study’s unconventional design and analytical methods, which are biased against Medtronic’s Endeavor stent in favor of Johnson & Johnson’s Cypher stent.

The SORT-OUT III study uses an unconventional methodology, which raises questions about the reproducibility, viability and applicability of the results.

Unlike randomized controlled trials with rigorous patient follow-up, SORT-OUT III is dependent on patient records from a national database.
The investigators themselves – not an independent clinical events committee – determined and verified stent thrombosis (ST), target lesion revascularization (TLR), myocardial infarction (MI) and restenosis.
SORT-OUT III is positioned as a “real-world” study, yet nearly 60 percent (3,344) of eligible patients were excluded in the analysis.
Procedure-related MIs were not captured, which may introduce bias, as other studies evaluating these two stents have demonstrated a high rate of peri-procedural MIs with the Cypher stent and a low rate with the Endeavor stent.
Differences in patient adherence to dual anti-platelet therapy regimens were not reported, despite the potential affect on safety outcomes.
For unknown reasons, the primary endpoint of this study was not presented at nine months, and the definition in the Lancet publication differs from what was originally stated in clinicaltrials.gov.

SORT-OUT III produced unexpectedly low event rates and inconsistent data for the Cypher stent compared to nearly every other trial in which the device has been evaluated.

SORT-OUT II, a previous study with a similar design conducted at the same centers, produced substantially different results for the Cypher stent:


Cypher Results	TLR @ 18 months	MACE @ 18 months

SORT-OUT III	2.0%	5%
SORT-OUT II	4.5%	10%

SORT-OUT III results for the Cypher stent at 18 months are inconsistently lower than those from a multitude of other trials utilizing the Cypher stent at 12 months:


Cypher Results	TLR @ 12 months	MACE @ 12 months

SORT-OUT III	2.0% @ 18mos	5% @ 18mos
LEADERS	7.3%	12.1%
SIRTAX	5.8%	8.4%
j-CYPHER	6.9%	--
SIRIUS	4.9%	8.3%
Pooled Cypher	4.3%	7.1%

SORT-OUT III’s 18-month results are short term: The long-term deficiencies of the Cypher stent demonstrated in multiple studies are not addressed by the short-term focus of SORT-OUT III.

Cypher has consistently shown late safety and efficacy catch-up out to five years:


	TLR @ 1 yr	TLR @ 5 yr	MACE @ 1 yr	MACE @ 5 yr	ST @ 1 yr	ST @ 5 yr

SIRTAX	5.8%	14.9%	8.3%	21.3%	2.0%	4.6%
ARTS II	8.4%	20.8%	10.6%	27.5%	1.4%	6.0%
Pooled Cypher	4.3%	9.6%	7.1%	21.5%	0.4%	1.8%

*All ST are ARC definite

Despite its flawed design and methods, SORT-OUT III shows the consistency of the Endeavor stent’s strong performance. While producing inconsistent finding for the Cypher stent, SORT-OUT III reinforces the low and durable event rates for the Endeavor stent observed in myriad other studies.

The Endeavor stent showed consistent TLR rates in SORT-OUT III (6.0% at 9 months) as compared to the real-world E-Five registry (5.1% at 12 months).
The rate of stent thrombosis for the Endeavor stent in SORT-OUT III at 18 months was 1.0 percent (ARC definite), with no new events after 9 months – consistent with all studies of the Endeavor stent.
The Endeavor program now has data on more than 2,100 Endeavor patients, with more than 1,200 followed to five years. The pooled data reinforce the Endeavor stent’s excellent long-term efficacy and safety profile (TLR at 5 years = 7%, ST at 5 years = 0.8%, VLST (yrs 1 to 5) = 0.2%).

Source: Medtronic, Inc.