That Health Rules

Just came back from Manila just this morning where I was one of the 5 invited speakers to share our views on the Avandia meta-analysis that sparked the controversy of this drug.  It was a well organized meeting and a very fruitful one as delegates ( enodcrinologists and diabetologists from all over the Philippines)  went home more enlightend by the fact tat avandia is actually safe or even safer than the other drugs sold in the market.

The highlight of the meeting was a detailed analysis of the article by Niesen published in NEJM in May 2007 by Dr Cecilia Gimeno who is herself an endocrinologist and a clinical epidemiologist from UP-PGH.

She highlighted why meta anaysis cant be trusted and what the flaws were in the article’s calculation of the statistics and data gathering.

TAKE HOME messages form the meeting which I want to share to my readers and patients as well:

1. The Meta analysis was not a good study since it compiled several small studies lump together to generate a bigger population BUT with each study had a different patient population with different outcomes ( not cardiovascular ) and had small number of subjects of short duration ( < 6 m).
2. The statistical analysis was flawed including omission of certain studies with no MI or CV deaths.  The exact nature of heart attack or death was not determined since the authors did not have the luxury of examining the data…they solely relied on results given to them. Did the patients take their other meds like for cholesterol or high blood pressure which in themselves can increase ones risk for heart attack and stroke?
3. Recalculation of the flawed statistics and numbers resulted in an almost the same risk of heart attack of patients on avandia and other drugs!!!!
4. The studies included in the analysis were short term ( < 6 m) … and short term studies do not predict long term results.  Similar problems were encountered by Metformin, Sulfonylureas and Pioglitazone where initial < 1 year studies showed increased heart attack risk but long term studies after 5-6 years showed benefit!
5. The 3 big prospective studies on avandia (ADOPT, DREAM and RECORD) which are randomized involving >4000 patients are true OUTcome studies which help clinicians formulate our treatment approach and which can be trusted showed that Avandia use is not associated with increased risk of heart attack compared to metformin or sulfonylurea!  In fact the use of a sulfonylurea was assessed to have higher cardiovascular death than avandia.  These studies are however masked by the controversy of one study of which the medical community deems contain numerous flaws!

My Conclusion of this matter: 

That Avandia is safe and is not associated with any increase in Heart Attack risk. 

Remember a patient with Diabetes in itself is already a Cardiovascular equivalent :  a Diabetic is equivalent to a ” non diabetic with a heart attack” in terms of his risk for cardiovascular mortality.  And if we consider the data of the Meta analysis as acceptable: the absolute risk is very small: a 0.1% absolute risk only…meaning 1 heart attack for every 1000 patients on avandia… BUT since the analysis was flawed… the absolute risk therefore of a patient on Avandia is really much lower than 0.1%  and the patient’s risk for heart attack is most likely just the inherent risk for being a Diabetic and nothing else!

For me it would be unfortunate if the benefits of this drug which includes: reducing ones risk to develop diabetes by 60 % ( DREAM) and reducing one risk to progression of diabetes by 60% compared to a sulfonylurea and 30% compared to a metformin (ADOPT) … are masked by this turn of events based on a flawed study!!!!

A Fact Can Harm If It Is Actually A Fiction!

This entry was posted on August 16, 2007 at 8:58 am and is filed under Medical News Bits, Personal Thoughts, The Diabetes Facts.