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November 08, 2007
VERITAS
Which means, of course, "truth," hubris at its best to so name a trial. And there are several.
One studying AMD (macular degeneration) "helps retinal physicians determine the best therapy for their patients" but hardly the truth.
The latest, the Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies, purports to determine if this new drug improves outcomes in patients with acute heart failure. (While we are on study names, this one relies on RITZ, ESCAPE and REVIVE. The footnotes also mention LIFE, DANAMI 2, MADIT-2, MIRACLE-ICD, OVERTURE, OCTAVE, ENABLE 1 & 2, CHRISTMAS, AFFIRM, RACE, WIZARD, AZACS, REMATCH, BNP trial and HARDBALL; CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE.)
Their conclusions: "Tezosentan also had no effect on the primary mortality/morbidity composite outcome (or any of the secondary outcomes), though even with this end point we had 80% power to detect a 25% relative risk reduction. Although disappointing and contrary to expectations based on the potential pathophysiological role of endothelin-1 in heart failure, our findings are consistent with earlier trials in chronic heart failure.27-30 In those trials, long-term treatment with oral endothelin receptor antagonists had no effect on left ventricular remodeling or clinical outcomes.27-30 Conceptually, however, short-term intravenous administration of a drug might have less prospect of showing a longer-term effect on morbidity and mortality outcomes, emphasizing the difficulty in evaluating new treatment for acute heart failure. Despite its hemodynamic actions, milrinone did not reduce morbidity and mortality in Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF), and nesiritide does not reduce morbidity or mortality in acute heart failure.31-33 Of course, it is also possible that a beneficial effect of tezosentan in one subgroup of patients may have been offset by harm in another, eg, patients with a low baseline blood pressure. VERITAS did not, however, have the statistical power for such an analysis, which in any case could only be hypothesis-generating.
"In summary, tezosentan, a treatment with "favorable" hemodynamic actions, failed to improve breathlessness or reduce fatal and nonfatal cardiovascular events in patients following an emergency admission to hospital with acute heart failure. So far, it has proved impossible to identify a therapeutic role for endothelin antagonists in patients with acute or chronic heart failure."
So from a mechanistic standpoint, this drug should work. Yet the previous studies on this type of drug showed no benefit. That was confirmed by this study.
This study was done at centers scattered around the world. It was paid for by the Swiss firmed that partnered with Genetech in 2000 to bring this drug into the US. They have known for years that it is not the wonder drug they thought. But I have no doubt it will continued to be pushed and tested until some sub-group of CHF patients is found who show some measurable but meaningless improvement.
At least the VERITAS revealed a small slice of the truth.
Posted by Robert Maddox at 11:22 PM | Comments (0)
EXCITE
I mention this study mostly to point out the ridiculous acronyms. This is the Extremity Constraint Induced Therapy Evaluation trial. They tested Constraint-induced movement therapy for stroke rehab, which as near as I can gather means you keep the patient from moving the good side to induce him to rehab the affected side.
And I do appreciate a good effort to make a memorable name.
Posted by Robert Maddox at 10:54 PM | Comments (0)
November 01, 2007
DVT Thrombolysis
Sometimes it pays to be behind the cutting edge in medicine. The Dallas VA Chief of endovascular surgery, Dr. Timaran, revealed his findings of the analysis of a sample of patients treated at various hospitals in 35 states from 1998-2003 for DVT with thrombolytics (instead of the traditional anticoagulation). Only 2% of the 800,000 patients admitted with DVT in the US were treated with thrombolytics, in 2003. This was an increase on both counts from 1998, when 0.4% of the 485,000 were so treated.
Thrombolytics (read clot-buster) seem intuitively better than anticoagulants (read blood-thinner - which is not exactly how it works). So away doctors went, their patients expecting the best and the latest.
So in 1998, there were 1,940 so treated. By 2003, that was increased to 16,800. Maybe somewhere around 50,000 patients so treated. Over half of these had major bleeds and there was a 5-fold increase in intracranial bleeding. The risk of in-hospital death increased by 75%. Now we are only talking about a mortality of a little over 1%. So in 2003, there were 8,000 deaths amongst the DVT patients, but almost 300 of the 16,800. That might have escaped the notice of the doctors involved, though the huge, expected increase in bleeds should not have.
Isn't this a simple case of leap before you think?
Posted by Robert Maddox at 11:41 PM | Comments (0)
Angiogram protection
FPN also reports from the Society for Academic Emergency Medicine that we should not rely on a history of a normal cath when evaluating a patient with chest pain. This is a most interesting study for a number of reasons. (Tell me if you hit that link that Dr. McMullan, the resident presenting this, doesn't look like Jack.) A retrospective cohort study followed all subjects with normal coronary angiograms between January and May of 2000 for 5 years.
Interesting aspect 1: 182 of the 598 angiograms in this ?5 months were completely normal (and the patients survived that hospitalization). By my rough calculation, that is 30.43%. Almost one-third of all caths done at U Cincinnati (I must be off on that guess because I would have guessed they did that many a month) were cold normal? Is the indication for a cath having a heart? I really wouldn't have guessed that many people walking on the street had normal coronaries, much less a cath population.
Interesting aspect 2: 45 (25%) underwent a repeat cath within the five years. They did not learn their lesson the first time.
Interesting aspect 3: Of those 45, 18 (40%) had developed CAD, and a few more had some irregularities. And 3 of these people died, compared to just one of the other 27 who maintained normal coronaries. Why this is a surprise confuses me.
IA 4: Of the 182 initially normal cath people, 18 (10%) developed CAD. (Actually, we don't know how many others may have, since I assume that these 18 are the aforementioned ones. What of those not cath'd?)
IA 5: In an interview, Dr. McMullen revealed that some of the patients were recath'd after just .4 years (I guess that means less than 5 months later, maybe even during May) and "bad disease" was found. He concludes (with no reason given though I agree with him) that the lesions were missed on the first cath. This is great. A cath can be read as normal falsely. But this is old news, since from the beginning the validity of cath interpretations have been challenged.
So remind me why we do caths?
Posted by Robert Maddox at 11:25 PM | Comments (0)
More from the FUTURE
So much to do treating sick people, and we are constantly treated to the same old garbage recycled. I posted several times on HPV and Gardasil, but they keep at it. According to Family Practice News, the FUTURE spokesman reported some new late-breaking findings to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
It seems that several subtypes (see the above links for a brief explanation) of HPV that are occasionally associated with high-grade cervical changes are also prevented by the quadrivalent vaccine, even though they are not included in the vaccine. This is not unexpected. They tested by species, rather than by individual subtypes, and the small print says why. There are so few of these rarer subtypes that they couldn't afford to actually study them. Also, remember that they are not looking at cancers or deaths prevented because these are years down the road. They are at persistent infection, and CIN 2/3 and AIS, a far-cry from cancer, lesions from which many women convert back to normal, unless they are damaged and will never have a normal Pap again.
This misinformation is being used to step up the ad campaign, and to extend it to men. This is wrong. That is a judgment.
Posted by Robert Maddox at 10:48 PM | Comments (0)