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I don't follow Lucentis / Avastin so my comments may be off base....but I'm not so sure that evidence marginally favoring Lucentis would be good for it's marketing. For just about any other drug you could use this to gain market share. But if your competitor (Avastin) was held back by a lack of evidence and now that evidence exists...it might get the bigger boost as a result. Outside of the US there is perhaps more cost concern (at least from the point of view of the payer, if not so much from physicians). If you can treat 40 times as many people with Avastin for the same money, and if the choice to use Lucentis might mean introducing eligibility criteria which wouldn't see everyone treated...what would you, as the payer, do? These are not my decisions to make, though I do have some experience sitting on advisory groups providing medical opinion relevant to such decisions. I would personally rather treat a lot of people with a slightly inferior drug than to let a substantial number of people go untreated.
Ouch...nice catch.
The potential sale of the pharmaceutical business is troubling to me. I assume it is intended to pre-empt those that want to take over the company by lessening the value they would recieve from doing the same thing (breaking the company up and selling parts off). Perhaps it is a good move to thwart a takeover bid but I never expected short term gains from the pharmaceutical division and was quite content to wait out the time until they were profitable. While I don't want a takeover bid to succeed ... it is sad to think that we might be forced to sell something that we always knew was going to take a long time to generate revenue. An emphasis on short term profits is toxic - how can you build anything of real value looking through that kind of lens?
So...they are repeatedly trying to take over biotech firms with depressed share prices. It is certainly not because they would have a better understanding of the business or make better managers than the people who have been working away at it for years. What is their general strategy? Presumably it needs to be making a quick buck...so..what...is it the selling off of assets that is key? How does that translate into lining their pockets? Incentive payments to (new) officers upon the sale? A overall stock price that is undervalued relative to the sum of the parts? Does the lack of debt / ability to debt finance going forward play any role that is attractive to them?
Thank you for doing all that very thorough groundwork.
I know little of the corporate world but I find it hard to believe that investors out for short term gain would be good for the long term growth of the company.
I have continually bought SRDX with each major collapse in share price over the last several years and expected to hold the stock for at least 10 years - likely longer. I find it very distressing that anyone not intending to be with the company long term would be at the wheel. I'm not looking for a gain over the next year or two, I'm looking for an asset that will appreciate over the longer haul.
I don't see how any of this could possibly be good for the long term investor.
Dew...do you have any thoughts?
Thats an interesting statement. "Both drug-eluting stents performed better than planned for the composite endpoint of MACE (4.9 % for XIENCE V® Stent vs. 5.2% for CYPHER® Stent); these data support the non-inferiority of the XIENCE stent over the CYPHER stent (non-inferiority p=0.01)." The p value for non-inferiority is given ... but you can (potentially) also show superiority in a non-inferiority trial. I wonder whether the trial also had a significant p-value for superiority. I know you said that this came from JNJ ... they may have ommitted that (more impactful) statement, if it were true, in the hopes of having people generalize non-inferiority to mean equivalence.
This is an interesting drug / indication. I would think the number of medically indicated users would be very small ... but wonder if there wouldn't be significant pressure on its use as a "lifestyle" drug given it essentially gives you a tan. Having said this...given it presumably needs to be implanted by a (medico-legally conscious) physician...perhaps that use wouldn't really evolve - or move to some other formulation that is either easier to access or less expensive (assuming it is or does become available in other forms, I know little about it beyond this press release).
From my journal service:
A Comparison of Two Drug-Eluting Stents Yields a Clear Winner
Overall rates of target-lesion failure were lower in everolimus-eluting stent recipients than in paclitaxel-eluting stent recipients.
In this prospective, multicenter, single-blind trial, 3687 patients undergoing elective stent implantation were randomized in a 2:1 ratio to receive second-generation everolimus-eluting stents (EES; XIENCE V) or first-generation paclitaxel-eluting stents (PES; TAXUS Express2). The study was sponsored by the EES manufacturer.
The primary composite endpoint of cardiac death, target-vessel myocardial infarction (MI), or ischemia-driven target-vessel revascularization at 1 year occurred in 4.2% of patients in the EES group versus 6.8% of those in the PES group (odds ratio, 0.62; P=0.001). Stent thrombosis (at 24 hours, 30 days, and 1 year) also occurred less frequently in the EES group than in the PES group (0.2% vs.0.8% overall; P=0.004). Target-lesion revascularization (TLR) was reduced by 45% overall in the EES group compared with the PES group; this benefit was consistent across all prespecified subgroups, with the notable exception of patients with diabetes, in whom the TLR rate was similar in both stent groups.
Comment: Previous studies of EES (and of the first-generation sirolimus-eluting stent) have demonstrated a reduction in intimal hyperplasia compared with PES. This large study also demonstrates a benefit with EES for important clinical endpoints, including TLR, cardiac death and target-vessel MI, and stent thrombosis. Based in part on advance knowledge of these results, interventionalists have already made EES the most frequently implanted stent in the U.S.
— Howard C. Herrmann, MD
Published in Journal Watch Cardiology May 12, 2010
Citation(s):
Stone GW et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med 2010 May 6; 362:1663.
Original article (Subscription may be required)
Medline abstract (Free)
Lange RA and Hillis LD. Second-generation drug-eluting coronary stents. N Engl J Med 2010 May 6; 362:1728.
ForSight Labs License:
http://finance.yahoo.com/news/SurModics-Licenses-bw-1944095031.html?x=0&.v=1
Dew
I am going to tactfully skirt the question by saying that my estimate of a timeline isn't worth much given that I don't really follow the device industry closely enough to know what normal is. Eight years sounds probable (i.e. better than 50% chance) to me but I'm not sure my guess is worth much. I have a reasonable appreciation of the stumbles likely on the course but not the time to finish the race. Like you, I do feel the uptake, given reasonable deliverability is achieved (and it probably would be), would be "Cypher-like" in terms of canabalizing other stents marketshare whenever it is introduced.
Do you (or anyone on the board) know what happened to the magnesium (another bioabsorbable) stent? If I remember correctly SRDX started to work with the company making it. I had hopes of a bioabsorbable SRDX coating on top of a bioabsorbable Mg stent. Sorry to be vague but I don't have the time to follow these things closely anymore...Pretty much just read this board.
FP
I agree that bioabsorbables will be the future if they can achieve even close to parity in clinical endpoints...in large part since it leaves the vessel easily able to recieve another stent from the interventional cardiologist down the road if needed. Good for the patients but it also makes things easier for the people who place them. Having said that, bioabsorbables will have lots of new technical hurdles to surmount and may take longer to get here than we might be led to believe. (Not that I have any sense of what an appropriate timeline would be - just that two steps forward one step back seems likely for any new endeavor.)
My journal service posted a similar summary (see below).
I would certainly see this as a big negative for Medtronic...and hopefully as a long term positive for surmodics...since the difference MIGHT be due to the coating / rate of release of the drug (i.e. phosphorylcholine coatings may not be the best way to go) rather than the difference in drugs eluted.
___________________________________________________________________________________________________
To Trial and Beyond: Sirolimus-Eluting Stents Outperform Zotarolimus-Eluting Stents
A randomized trial design combined with follow-up data from a Danish national registry generates compelling evidence of superiority.
Recent concerns about late stent thrombosis and evidence of delayed in-stent restenosis have fueled the development of a new generation of drug-eluting stents. To compare the novel zotarolimus-eluting stent with the well-established sirolimus-eluting stent, investigators in Denmark conducted a single-blind, all-comer, manufacturer-funded trial in patients undergoing percutaneous coronary intervention for chronic stable coronary artery disease or acute coronary syndromes (ACS). A total of 2332 patients (mean age, 64; 73% men) with 3230 coronary lesions were randomly assigned to receive zotarolimus-eluting or sirolimus-eluting stents. Follow-up data at 9 and 18 months were obtained from national administrative and healthcare registries.
The incidence of the composite endpoint — cardiac death, myocardial infarction (MI), and target-vessel revascularization — was significantly higher in the zotarolimus-eluting stent group than in the sirolimus-eluting stent group at 9 months (6% vs. 3%; P=0.0002) and 18 months (10% vs. 5%; P<0.0001). All cause-mortality was 2% in both groups at 9 months but was significantly higher in the zotarolimus-eluting stent group at 18 months (4% vs. 3%; P=0.035).
Comment: These findings suggest that sirolimus-eluting stents are superior to zotarolimus-eluting stents and highlight the importance of longer follow-up times in drug-eluting stent trials. The innovative use of a national healthcare database rather than follow-up study visits to record clinical outcomes contributed to lower-than-expected event rates in both groups. However, this approach seems cost-saving and allowed inclusion of a relatively high number of patients with ACS, multivessel disease, or complex lesions who would normally be excluded from contemporary clinical trials.
— Beat J. Meyer, MD
Published in Journal Watch Cardiology March 15, 2010
Citation(s):
Rasmussen K et al. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): A randomised controlled superiority trial. Lancet 2010 Mar 15; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(10)60208-5)
Webster MWI and Ormiston JA. Sorting out drug-eluting stents. Lancet 2010 Mar 15; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(10)60402-3)
Nice to see you back Aslan.
I agree that the results are interesting...and perhaps meaningful...in that better procedural skill and post-op nursing care / resources are a likely reason for the difference. But without randomization all sorts of counfounders can potentially account for observed results. That being said, it would be very difficult to perform a randomized trial to answer such a question...so this is likely as good an answer as you will get to the effect of procedural volume on outcomes.
Thanks for the replies. End of 2009 for European approval sounds encouraging for SRDX as it is a promising stent. I think fully biodegradable stents is where the market will eventually go but I would wager there will be unforeseen technical hurdles which will delay its arrival for several years. Drug eluting balloons are an intriguing concept - in part because they let you choose your favorite BMS to follow. There was info in the uncoated stent days that suggested thinner struts might produce less restenosis - and thin struts are difficult to accomplish when you are applying a coating on top of the struts.
The trial which has always made the most sense to me is the best in class BMS with a couple of days peri-procedural oral prednisone versus the best in class DES. This, of course, runs contrary to the interests of the device companies which fund such research (as it is a much less expensive option) so you won’t see it happen (despite some promising early work).
I don't really follow these things closely anymore but I remember reports of great deliverability (maneuverability) with the Conor (now Nevo)stent. If Nevo continues to get good clinical results, the biodegradeable polymer and deliverability advantages could indeed lead to a large marketshare. Does anyone have a sense of the timeline for Nevo to become available? Has JNJ said anything about when they might expect European availability in particular?
I agree with Dew. You would need to be able to show significant advantage (which they didn't) for the extra time and manipulation to be felt warranted.
The ARVO abstracts:
http://arvo.abstractsonline.com/Plan/SSResults.aspx
From my journal service:
__________________________________________________________________________________
A Bioabsorbable Drug-Eluting Stent: 2-Year Data
Favorable findings from a feasibility study move us a step closer to reducing the thrombogenic risk of coronary stenting.
Theoretically, an effective bioabsorbable stent would temporarily scaffold the vessel wall, reduce neointima proliferation without increasing the risk for late thrombosis, and restore vascular integrity. Early results of a small, manufacturer-funded, open-label study of a bioabsorbable, polylactic acid stent coated with a more rapidly absorbable, everolimus-eluting polylactic acid layer were promising (JW Cardiol Mar 26 2008). The present report contains the 2-year follow-up results obtained with multislice CT, angiography, intravascular ultrasound, and optical coherence tomography (OCT).
Clinical outcomes were available for 29 of 30 patients with single, de novo coronary lesions treated with 3 mm x 12 mm stents or with 3 mm x 18 mm stents: No new adverse cardiac events occurred between 6 and 24 months. Multislice CT assessment at 18 months in 25 patients showed a mean diameter stenosis of 19%. At 2-year angiography, the mean in-stent late loss of 0.48 mm and diameter stenosis of 27% did not differ significantly from the findings at 6 months. At 6 months, OCT had revealed a thin layer of intima on almost all stent struts, but 7.0% showed malapposition; at 2 years, no features were discernible at 34.5% of strut locations, and the remaining apparent struts were fully apposed. Methergin or acetylcholine administration (terminated by nitroglycerin) produced vasomotion at the stented sites and in adjacent arteries.
Comment: These findings suggest that the previously reported early safety and benefits of a bioabsorbable everolimus-eluting stent are sustainable. However, this was a small trial, limited by a very small number of truly serial observations by multiple imaging modalities. Larger trials in patients with more-complex lesions are needed before we can consider bioabsorbable stents a breakthrough in reducing the risk for subacute thrombogenesis.
— Beat J. Meyer, MD
Published in Journal Watch Cardiology March 25, 2009
Citation(s):
Serruys PW et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet 2009 Mar 14; 373:897.
Medline abstract (Free)
Colombo A and Sharp ASP. The bioabsorbable stent as a virtual prosthesis. Lancet 2009 Mar 14; 373:869.
Medline abstract (Free)
I don't know if this has already been circulated but may be of interest:
http://www.paragon-ip.com/newsroom/Nexeon_SurModics_Renal_PR012709.pdf
The Octoplus writedown may have happened now simply because the bottom is falling out of everything else - and a bad news quarter was inevitable. I don't make these kinds of decisions for a living, but I see some wisdom in getting all your bad news out (and over with) at the same time. The overall market collapse and Merk anouncement dwarf everything else. In an otherwise uneventful quarter the Octoplus writedown may have translated into a greater hit to the share price.
Ouch!! I normally ignore price fluctuations but an 11% drop is surprising. Is there anything SRDX specific to explain this, or is it just the whole market falling (which SRDX has been relatively immune to in the past)
I assume Surmodics has rights of some sort to a particular method of encapsulating, while Novocell holds the more important patent to the end result (PEG encapsulated cells).
Apparently the word processor for i-hub can't use the greek beta symbol and the article I posted has changed the term pancreatic beta cell into some peculiar symbol and number string. I think the article below is free of such errors now.
__________________________________________________________
Who Needs Stem Cells? Reprogramming One Adult Cell Directly into Another
Insertion of three genes transformed adult pancreatic exocrine cells into functional Beta-cells in mice.
We were all taught that undifferentiated embryonic cells progressively become differentiated adult cells — and that there is no turning back. Yet, we’ve known for 40 years that if the nucleus of an adult cell is placed into an enucleated egg, the genes of that adult cell are reprogrammed to an embryonic state (although such transfer has not been accomplished successfully in human cells). Then, in 2007, genes were introduced into complete adult cells — first mouse, then human — that reprogrammed adult cells into the equivalent of embryonic stem cells (JW Nov 29 2007).
Harvard researchers identified three genes that always are turned on in pancreatic Beta-cells. They inserted these genes into a viral vector that homed to pancreatic exocrine cells (which do not produce insulin) and then injected the vector into living mice. More than 20% of infected cells were reprogrammed into glucose-sensing, insulin-producing Beta-cells. When endogenous mouse Beta-cells were destroyed with streptozotocin, subsequent transfection with the viral insulin vector caused insulin levels to rise and glucose levels to fall in diabetic mice — an effect that persisted for at least 9 weeks.
Comment: This remarkable report indicates that, at least in pancreatic cells in mice, one adult cell can be transformed into another, in vivo, without first becoming an undifferentiated stem cell. If the same could be accomplished (without unintended effects) in humans, this technique obviously could become a treatment for diabetes.
— Anthony L. Komaroff, MD
Published in Journal Watch General Medicine September 23, 2008
Citation(s):
Zhou Q et al. In vivo reprogramming of adult pancreatic exocrine cells to Beta-cells. Nature 2008 Aug 27; [e-pub ahead of print]. (http://dx.doi.org/10.1038/nature07314)
From my journal service:
______________________________________________________________
Who Needs Stem Cells? Reprogramming One Adult Cell Directly into Another
Insertion of three genes transformed adult pancreatic exocrine cells into functional β-cells in mice.
We were all taught that undifferentiated embryonic cells progressively become differentiated adult cells — and that there is no turning back. Yet, we’ve known for 40 years that if the nucleus of an adult cell is placed into an enucleated egg, the genes of that adult cell are reprogrammed to an embryonic state (although such transfer has not been accomplished successfully in human cells). Then, in 2007, genes were introduced into complete adult cells — first mouse, then human — that reprogrammed adult cells into the equivalent of embryonic stem cells (JW Nov 29 2007).
Harvard researchers identified three genes that always are turned on in pancreatic β-cells. They inserted these genes into a viral vector that homed to pancreatic exocrine cells (which do not produce insulin) and then injected the vector into living mice. More than 20% of infected cells were reprogrammed into glucose-sensing, insulin-producing β-cells. When endogenous mouse β-cells were destroyed with streptozotocin, subsequent transfection with the viral insulin vector caused insulin levels to rise and glucose levels to fall in diabetic mice — an effect that persisted for at least 9 weeks.
Comment: This remarkable report indicates that, at least in pancreatic cells in mice, one adult cell can be transformed into another, in vivo, without first becoming an undifferentiated stem cell. If the same could be accomplished (without unintended effects) in humans, this technique obviously could become a treatment for diabetes.
— Anthony L. Komaroff, MD
Published in Journal Watch General Medicine September 23, 2008
Citation(s):
Zhou Q et al. In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 2008 Aug 27; [e-pub ahead of print]. (http://dx.doi.org/10.1038/nature07314)
You think the InnoRx platform would have no use even as a means of delivering a lucentis-like molecule? Could you elaborate?
A similar summary from my journal service:
______________________________________________________________
Stenting vs. Medical Management of Stable Coronary Disease: More Outcomes from COURAGE
Perhaps it’s time to change practice in the U.S.
In the landmark COURAGE trial, percutaneous coronary intervention (PCI; usually stenting) — added to optimal medical therapy — did not lower rates of death or myocardial infarction, compared with optimal medical therapy alone in 2287 patients with stable coronary artery disease (JW Mar 29 2007). Now, the COURAGE researchers report on symptoms and quality of life in this cohort during 3 years of follow-up.
Patients in both groups improved during the first year, but a significantly larger proportion of PCI patients than medical-therapy patients became angina-free (e.g., 56% vs. 47% at 6 months). However, between-group differences narrowed by 2 years and were no longer significant by 3 years. Similar patterns were noted for angina-symptom and quality-of-life scores — an initial small edge for the PCI group but few or no differences between groups by 3 years. PCI benefit was confined primarily to patients who experienced angina at least weekly; those with less frequent angina garnered no significant benefits from PCI.
Comment: Among a subset of patients with stable angina, PCI confers a small incremental benefit in control of angina during the first year or two after the procedure. Interestingly, symptoms improved among medically managed patients during the first 3 months of the trial; this finding suggests that patients’ medical management had not been optimal before enrollment in COURAGE. Editorialists provide this take-home message: Pursue optimal medical therapy initially and use PCI if medical therapy is ineffective. However, they acknowledge that this paradigm is essentially opposite of current practice in the U.S., where PCI usually is a first-line strategy, not only for patients with stable angina, but also for patients with asymptomatic coronary disease that is discovered when noninvasive testing leads to coronary angiography.
— Allan S. Brett, MD
Published in Journal Watch General Medicine August 13, 2008
Citation(s):
Weintraub WS et al. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med 2008 Aug 14; 359:677.
Original article (Subscription may be required)
Peterson ED and Rumsfeld JS. Finding the courage to reconsider medical therapy for stable angina. N Engl J Med 2008 Aug 14; 359:751.
Thanks for locating the transcript reference. I can see that, even if they stopped making Cypher, JNJ could choose to maintain the license to block others using the same sirolimus / polymer combo - but the transcript suggests JNJ can let the license go, and stop the royalty payments, if it is in their best interest. They don't have to keep paying if they don't care about keeping others away from the technology.
I'm not so sure SRDX would get a royalty if JNJ was no longer selling Cypher at all. I would have thought they meant that, if there were still product sales, a minimum royalty would apply.
The biggest news for me was their confidence that another opthalmology license would likely be signed this quarter. I realize it isn't likely to be as big as the Merck agreement, given it won't include ivation-TA, but even one third (uninformed guess) the value would be a big contract.
You might be thinking of the Medtronic DES (Endeavor).
Thanks for the info...the direct page link is:
http://www.clinicaltrials.gov/ct2/show/NCT00692614?term=NCT00692614&rank=1
I know they don't list IOP as a secondary outcome but it will still be measured / reported. They aren't trying to gloss over it. It just isn't being singled out for the purpose of the stats analysis.
From a Journal Summary Service:
Drug-Eluting Stents Have Improved Outcomes, but Without Effect on Death Rates
Patients with drug-eluting stents face less need for revascularization than those with bare-metal stents, but their risk for death or MI is similar, reports JAMA.
Researchers compared two cohorts comprising some 67,000 Medicare patients. The first consisted of those treated with bare-metal stents, immediately before drug-eluting stents became available. The second contained patients treated later, with about two-thirds receiving drug-eluting stents and the rest receiving bare-metal stents.
Through 2 years' follow-up, patients in the era of drug-eluting stents showed less risk for revascularization and bypass surgery than those treated earlier, but their risk for death or ST-elevation MI was similar.
In Journal Watch Cardiology, Howard C. Herrmann comments: "An increased risk for late stent thrombosis has been associated with [drug-eluting stents] ... however, if such an increase occurred in this study, it was more than offset by a decrease in the risk for restenosis and events arising from its treatment."
I've never heard of using ultrasound for drug delivery. There is a (relatively untapped) technique called iontophoresis which applies a drug in a gel and then uses an electric current to supposedly transmit it to deeper tissues. I am only peripherally aware of it - with the use I had heard of being to deliver NSAIDs for soft tissue injuries. I can't really speak to it's efficacy, although it was suggested to be useful by the individual I spoke with (a PhD candidate who studied tendinopathy).
I agree completely that joint replacements will continue to climb in numbers as the boomers push into those years but I'm not sure that surface modification will find an easy fit here. I wouldn't expect the articular surface to be an area where coatings are applied because they wouldn't likely be durable enough. Even the metal / plastic surfaces slowly erode over years and you can find small amounts of these materials at distant sites in the body (hopefully, but not necessarily, without consequence). The stems of the implant would clearly benefit from surface modification in the hopes it would integrate better with the bone but I doubt this would be a simple drug eluting polymer coating - more likely a textured metal surface either uncoated or (wishful thinking) perhaps having an ECM type coating modification. As for antibacterial coatings...not impossible but if it isn't going to include the articular surface and might impede integration of the stem with the bone I wouldn't put out a lot of hope for it. Maybe the ECM coating will find a place. The other ortho markets are not so big. The antibiotic beads were never going to be a blockbuster, in part because such things are already being compounded and available to some degree. No particular company can market it but certain pharmacists have the ability to create them (not sure what the matrix is)
Thanks. I imagine bundling of products and longer term contracts signed in advance of a new stents arrival would slow a new stents uptake even if it was percieved as superior. The Cypher balloon will continue to deflate ... but not overnight.
Anyone know the XIENCE marketshare in Europe?
From my journal service:
________________________________________________________________________________________________________________________________
A New Drug-Eluting Stent on the Horizon
Everolimus-eluting stents perform well in a comparison with paclitaxel-eluting stents, setting the stage for FDA approval and — more important — long-term outcome studies.
Manufacturers of drug-eluting stents (DES) strive to improve device safety and efficacy. Three DES are now available in the U.S., and even more are available in other countries. Based on the results of this manufacturer-sponsored, randomized, multicenter trial, the everolimus-eluting stent (EES) is poised to become the next entry into the U.S. market.
A total of 1002 patients undergoing elective PCI for one or two de novo lesions were randomized to receive an EES or a paclitaxel-eluting stent (PES) at a two-to-one ratio. Of 564 patients who were assigned to receive angiographic follow-up at 8 months, results were available for 77%. At 8 months, in-segment late loss (the primary endpoint) was 0.14 mm in the EES group versus 0.28 mm in the PES group (P=0.004). In-stent late loss was 0.16 mm in the EES group and 0.31 mm in the PES group (P=0.006). In-segment restenosis trended lower with EES than with PES (4.7% vs. 8.9%; P=0.07), but target-vessel revascularization (TVR) rates were similar between groups. At 1 year, no between-group differences were seen in rates of death, MI, or early or late stent thrombosis (defined various ways), when examined individually. However, the composite rate of death, MI, and TVR at 1 year was lower in the EES group than in the PES group (6.0% vs. 10.3%; P=0.02).
Comment: The everolimus-eluting stent — like the sirolimus-eluting stent (SES) — reduced intimal hyperplasia more effectively than PES. However, this advantage did not translate into clinically important reductions in restenosis or target-vessel revascularization, although the observed trend toward lower restenosis rates with EES might have been significant in more-complex patient and lesion subsets. The observed benefits may relate to the device’s thinner polymer and stent-strut width. I believe that the EES will be marketed as more deliverable than the SES, but it will be important to continue to gather data in larger populations (including off-label usage) and for a longer follow-up period to confirm the safety and effectiveness of this device.
— Howard C. Herrmann, MD
Published in Journal Watch Cardiology May 7, 2008
Citation(s):
Stone GW et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: A randomized trial. JAMA 2008 Apr 23; 299:1903.
Original article (Subscription may be required)
Medline abstract (Free)
Patel MR and Holmes DR Jr. Next-generation drug-eluting stents: A spirited step forward or more of the same. JAMA 2008 Apr 23; 299:1952.
Another article from my journal service:
________________________________________________________________________________________________________________________________
Are High-Dose Tirofiban and Drug-Eluting Stents Best for STEMI?
Results of a randomized study favor SES over BMS and show a high-dose bolus of tirofiban to be as good as abciximab.
In this randomized, 2x2 factorial trial, investigators in Italy, Spain, and Argentina compared sirolimus-eluting stents (SES) with bare-metal stents (BMS) and abciximab with tirofiban in 745 patients with acute ST-segment-elevation MI. Abciximab was administered using standard dosing (0.250 mg/kg bolus followed by 12-hour infusion at 0.125 µg/kg/min), but tirofiban was administered as a higher-than-label bolus of 25.00 µg/kg followed by an 18- to 24-hour infusion at 0.15 µg/kg/min. Baseline and procedural characteristics were similar among the four groups.
Eighty-four percent of patients in the abciximab group and 85% of those in the tirofiban group achieved the primary endpoint of 50% ST-segment resolution within 90 minutes of percutaneous coronary intervention (P=0.53). At 30 days, no between-group difference was seen in the composite rate of death, reinfarction or target-vessel revascularization (TVR; about 4% in both). The rates of major and minor bleeding were also similar in both groups, although moderate or severe thrombocytopenia occurred in more patients assigned to abciximab than to tirofiban (4.0% vs. 0.8%, P=0.004).
At 8 months, the composite rate of death, reinfarction, or TVR was lower in the SES group (7.8%) than in the BMS group (14.5%, P=0.004), a difference driven mostly by a reduction in TVR of almost 70% in the SES group. Stent thrombosis rates were similar in all four groups, despite the fact that dual antiplatelet therapy was mandated for only 3 months (66% of SES patients were no longer taking thienopyridines by 8 months).
Comment: Previous comparisons of abciximab and tirofiban in PCI found abciximab to be superior, possibly because the loading dose of tirofiban was inadequate. These findings support this theory by demonstrating the noninferiority of a high bolus dose of tirofiban. The results also confirm the benefit of sirolimus-eluting stents, which reduced target-vessel revascularization compared with bare-metal stents without increasing the risk for stent thrombosis. The adoption of this combination in the U.S. may be hindered by labeling: Tirofiban labeling does not include the high-bolus dose and SES labeling does not include acute MI as an indication. Nevertheless, these results are reassuring to clinicians who wish to expand their arsenal of treatments for acute MI.
— Howard C. Herrmann, MD
Published in Journal Watch Cardiology April 30, 2008
Citation(s):
Valgimigli M et al. Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: The MULTISTRATEGY randomized trial. JAMA 2008 Apr 16; 299:1788.
From my journal service:
"Reprogrammed" Stem Cells Successfully Treat Parkinson Disease in Rats
Induced pluripotent stem cells transformed chemically into dopaminergic neurons hold promise as a treatment for this movement disorder.
In 2007, adult human cells were "reprogrammed" by genetic manipulation into cells with the potential of embryonic stem cells — a landmark event in the history of stem cell biology (Journal Watch Top Story Dec 28 2007). Similarly reprogrammed cells from mice are capable of curing sickle cell anemia in mice (Journal Watch Dec 13 2007).
Reprogramming stem cells to combat a specific disease now has been achieved in a rat model of Parkinson disease (PD). First, the research team caused a PD-like condition by using a toxin that kills dopaminergic neurons in the midbrain. Then, the investigators reprogrammed adult fibroblasts from these rats to become induced pluripotent stem (iPS) cells, caused these iPS cells to multiply in cell culture, used chemical signals to turn them into dopaminergic neurons, and injected them into the midbrains of the rats. In eight of nine treated rats, the grafted cells integrated into the midbrain, produced dopamine, and greatly improved the PD-like movement disorder. No such benefits were seen in sham-grafted rats.
Comment: Reprogrammed (i.e., iPS) cells have two potential virtues in transplantation therapy. They are "self" (so no immunosuppression is required), and they do not come from embryos, thus they raise no ethical questions. This work in parkinsonian rats, like the previous report about mice with sickle cell disease, shows that their theoretical promise is very real — at least in animals.
— Anthony L. Komaroff, MD
Published in Journal Watch General Medicine April 24, 2008
Citation(s):
Wernig M et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci U S A 2008 Apr 15; 105:5856.
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