Tuesday, May 29, 2012

More on earlier blog regarding statins,primary prevention,drinking water

My earlier blog commentary on the recent Lancet meta-analysis on outcomes of primary prevention trials in patients designated as "low risk"was done hastily and driven largely by my basic skepticism regarding meta-analyses and betting the farm on a single such study. A much more thoughtful and important analysis can be found here.

It was written by Dr. David Newman,an ER physician who authored the book entitled
Hippocrates Shadow:Secrets from the House of Medicine.

What apparently made the results of the recent Lance Meta-analysis different from a number of meta-analyses which found contradicting results was that the current study looked at the mortality data on those low risk patients who experienced a 40 mg or more decrement in the LDL following the institution of statin therapy.So the measure of interest was not the outcome of all low risk subjects treated with statins just those who had a favorable response to statins.

in Dr. Newman's words:

"Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However the authors’ conclusions imply that they answered a different, much bigger question. And that is not a true story."


h/t to the tireless Dr. Roy Poses whose comments on my earlier posting alerted me to this line of thinking.


addendum: added 5/31/2012. I should have known Dr. Newman's comments were not go unchallenged and all such challenges not from hired guns at Pharma. Here are some arguments raised by Newman's critique.Thanks to the always informative and up to date web site ,Cardiobrief.

Monday, May 28, 2012

PSA and "moderate certainty" Don't screen says the central authority

See here for the latest pronouncement of the USPSTF regarding PSA screening.In a word "don't"

I suppose "moderate certainty" is a notch or two below"absolute certainty" The USPSTF made their dictum on the basis of moderate certainty.

Dictum is the correct noun since it seems according to ACA the determinations of the USPSTF will become the rules for CMS and how long will the other third party payers take to follow their lead?

DrRich ( aka Dr. Richard Fogoros of the blog, The Covert Rationing Blog,)seems to actually have read much if not most of the lengthy ACA and said this about the new role of USPSTF quoting chapter and verse.

Obamacare, which is now the law of the land, makes the USPSTF the final arbiter of which preventive services are to be covered by private insurers (Section 2713), by Medicare (Section 4105), and by Medicaid (Section 4106). Only those that have achieved a grade of A or B by the USPSTF will be covered. And if you believe you will be able to purchase for yourself PSA screening (or any other medical service which Obamacare has decided not to cover) you have not been paying attention. Perhaps you can do so today (if you’re not on Medicare or Medicaid), but probably not for long.

The conclusions of the USPMTF in regard to PSA are presented as a scientific conclusion although one that apparently only reaches the level of moderate certainty. However, opponents of that conclusion have made cogent arguments. See here.

There is in fact evidence that PSA can save some lives but the disagreement is in how to determine ( or who shall determine) if the benefit exceeds the cost or is the ratio inverted. In the judgement of the panel the benefit does not exceed the risk. This is a value judgement not a scientific judgement. It is not an argument raised only by those who are ignorant of statistical concepts or driven by financial concerns as was claimed recently by the chair of the panel.( See here for my comments regarding that.)

Thomas Sowell has written that in the last fifty or more years there has been a major shift in the " locus of decision making" moving toward a more centrally located site.It has taken several forms; from the family to the state,from the local government to the central government and now from the individual patient with counseling from his physician to a panel whose pronouncements will be determinative.

Saturday, May 26, 2012

Is aspirin the new warfarin regarding venous thrombosis-No,but.....

I had thought that aspirin was for the most part not considered very useful as a medication that could prevent venous thrombosis but had an important role in preventing arterial thrombosis .Now we have evidence from a clinical trial that aspirin may be useful in prevention of venous thrombosis.See here. As the discussion section of the NEJM article (linked below) indicated there had been previous published data suggesting aspirin's value in venous thrombosis prevention but for some reason aspirin never seemed to achieve a reputation as a useful venous thrombosis prevention.

The trial,WARFASA,studied patients who had received 6-18 months of standard therapy for venous thromboembolism (VTE) .The treatment group received 100 mg aspirin per day and the recurrence of VTE was significantly less in the treatment group. The recurrence rate was 11.2 events/years in the control group versus 6.6 in the aspirin group with one instance of major bleeding in each group. The recurrence rate seen in the control group is compatible with the usually quoted 10% per year recurrence in patient with unprovoked VTE after anticoagulation therapy is discontinued. See here for the study published in NEJM.

The study was done in Italy where the 100 mg aspirin tablet is available.As far as I can tell in the US,we have only a 80 mg. aspirin.and the regular strength aspirin.

Of course, aspirin is not the new warfarin but might it have a role in the longer term treatment of a patient with unprovoked VTE? Dr. Stephen Moll, a hematologist with special interest in thrombosis offers his take on this study and how he plans to use aspirin in some of his VTE patients. See here for the commentary on his blog ClotConnect.

Another similar trial is underway ( the ASPIRE trial ) is scheduled to offer some results later in 2012 and hopefully will be able to offer confirmation of this rather small trial.

Interestingly,the 9th edition of the ACCP clinical guidelines on antithrombolic therapy and prevention recommends against the use of aspirin in the prevention of VTE in long haul flights.See here.

Tuesday, May 22, 2012

Coarse grain data aka Big Data medicine and risk of the z-Pak

The EP cardiologist and long time medical blogger, Dr Wes, hits a home run with this commentary about the recent study that claimed a relationship between cardiac death and the use of azitromycin and some of the bigger issues with what he calls "Big Data Medicine".

The article in question appeared in a recent issue of the big impact medicine journal the, NEJM.
See here.

The authors reported an increased risk of cardiovascular death with a hazard ratio of 2.49 (1.38--4.5) and an overall mortality risk of 2.02 (1.24 --3.30). The ratios are a bit too high for me to make my usual comments ( see here ) about relative risks less than 2.

Azitromycin has been associated with a prolonged Q-T interval so the door is open to speculate about a pathophysiological mechanism that could explain the results if the association is real and not the artifact of crunching large numbers through the filters of a cascade of assumptions. How long will it be before we will be treated to an alternative statistical story from the epidemiologists at Pfizer which has been marketing Zithromax since 1991. Meanwhile the FDA promises to take the matter under consideration.

More data to recommend putting statins in the drinking water?

There seems to be little controversy regarding treating patients with coronary artery disease with statins,what we call secondary prevention. Primary prevention, treating patients, who have no clinical evidence of heart disease,with statins is another matter being more than a little controversial.

Now we have a new meta-analysis that concluded primary prevention is a good idea. See here for a discussion of that study which reported a reduction in cardio-vascular mortality and all cause mortality in so called low risk patients. On the other hand (clinicians may yearn for the mythical one handed epidemiologist) a large meta-analysis by Dr. K. Ray and colleagues found no benefit in terms of all cause mortality.see here.

A few years ago I felt reasonably confident that I could a)determine a person's cardiac risk with a risk equation and b) advise that person about taking statins to lower his risk. I am much less sure about both those two things now but I still obstinately take pravastatin. In regard to risk equations I said all I can say about that in this several years old post entitled "Individual risk assessment,a peculiar,elusive,ambiguous concept." I would add another modifier, "faith based".

So how good can the risk equations ( yes there are more than one for predicting risk of coronary heart disease events and death ) be when studies perched on the highest rung on the ladder of evidence based medicines give contradictory results?