Saturday, April 26, 2008

Let's give everyone Beta Blockers in Heart Failure!

some people have been talking about this wonderful polymorphism in African Americans. This polymoprhism is in the GRK5 gene. What does it do? Well, before I look at any polymophism I always ask. "What does the gene do?" GRK5, short for G-coupled protein receptor kinase, this kinase acts as a switch that essentially turns off receptors. Such receptors bind catecholamines, which are sympathetic system neurotransmitters like epinephrine and norepineprhine. They also bind peptide hormones such as angiotensin, which is implicated in high blood pressure. For the lay person....this gene helps regulate response to adrenaline and other hormones that are in overdrive with stress and in this case heart failure (the inability of your heart to pump your blood).

Why is this polymoprhism important? For a long time there was a thought that Beta Blockers did not help African Americans in Heart Failure. I kept thinking "This is stupid. Not everyone of the same race is the same." More importantly the data with which we applied this broad racist thinking was not the BEST. This applies for many things in medicine. We often jump to conclusions when not thinking genomically. The age old debate about coffee is the same story as well. Until viewed in the light of genetics and CYP polymorphisms, one could say that a cup of joe is bad or good for you. It turns out, if you process caffeine poorly, big are at increased risk. If you metabolize big deal.

So how does this help us treat heart failure in African Americans? Here's the zinger from the author Gerald W. Dorn II, M.D....

“By mimicking the effect of beta blockers, the genetic variant makes it appear as if beta blockers aren’t effective in these patients,” he explains. “But although beta blockers have no additional benefit in heart failure patients with the variant, they are equally effective in Caucasian and African-American patients without the variant.”

Bingo!! Clinically applicability. But here's the kicker. Will testing for this be clinically feasible? Will the cost be feasible? Some are saying no...including the guy who I just quoted

"That doesn't mean African-Americans with heart failure need to be tested for the genetic variant to decide whether to take beta blockers," Dorn says. "Under the supervision of a cardiologist, beta blockers have very low risk but huge benefits, and I am comfortable prescribing them to any heart failure patients who do not have a specific contraindication to the drug."

What the hell? He just said that the risk benefit was well in favor of benefit for all heart failure patients. This 50 year old white guy(he graduated med school 27 years ago), just proved he was a 50 year old white guy operating under the old set of evidence based instructions. He just said "I am willing to spend the taxpayers' money on a medication even if it doesn't benefit the patient, because I think it would be too confusing to test the patient for this polymoprhism during the first 10 days of therapy"

But I am certain he doesn't see it that way. He sees it as, "I see 20-30 heart failure patients a day. Why? Because my operating expense has gone up and my insurance payments have gone down. So I don't have the time to test these I just spend the insurers money on these meds. Why? Because they work!" And that my friends is how everyone ends up overmedicated!

I wonder if he ever considered that the money saved and risk averted could be a nice way to reimburse him for the new model of healthcare this nation is now demanding? Hmmm.....Might be one way to get the 50 year old white men on board with Genomic Medicine......"Pay for appropriate usage or non-usage of medications" Listen, don't get me wrong. Beta blockade in heart failure is cost effective. But imagine how much more bang you would get for your buck if you could squeeze that much more effectiveness out of it.

We really need to know how this can affect care. This could be a great clinical example. Berci at Scienceroll is compiling a database of clinical examples. I think that as we see these cases add up, we will then begin to realize the power of Genomic Medicine.

The Sherpa Says:

The only constant is change, and times, they are a changing. I am blown away that this researcher didn't investigate whether it might be worthwhile to test these patients rather than let them be guinea pigs simply in the name of evidence based medicine. Genomic Medicine is here. The passage of GINA heralds its arrival. Even Burrill and Company believes it, so it must be true! To all my colleagues out there....Be Prepared.


Misha said...

G.I. Joe lives!

Steve Murphy MD said...

So now you Know......