"Science" Takes ACLS Backwards

Food and Drug Administration (FDA) regulations have become the new pathway to riches for the pharmaceutical industry.

First, there was generic colchicine, used for years and years to treat gout for  pennies a pill.  The only problem was, there wasn't an FDA trial proving colchicine's efficacy in the treatment of gout.  Takeda Pharmaceutical, seeing the opening, performed a trial and rebranded the formerly generic colchicine to Colcrys®, "the only authorized generic indicated to prevent and treat gout attacks."  And how much does Colcrys® cost?  Just $203 for thirty tablets at Costco.

But that's not all.

Today I learned that generic vasopressin (which can be stored at room temperature in stable form on crash carts), must be switched to the FDA-approved brand called Vasostrict® that requires dilution and refrigeration.  It seems the generic form of vasopressin will no longer be available to be kept on crash carts since it's not "FDA-approved" for the indication of "increasing blood pressure in adults with vasodilatory shock (post-cardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines." Vasostrict®, on the other hand, is "now the first and only vasopressin injection, USP, product with an NDA approved by the FDA." The catch is, it must diluted before use and discarded after 18 hrs (or after 24 hrs if refrigerated). This little regulatory quirk is a big deal for America's hospitals looking to save costs.

But hey, why should we worry about costs in health care?  After all, you can never be too safe.

-Wes

The Malignancy of Heart Failure

With the release of the results of the EVEREST trial at the American College of Cardiology Meeting in New Orleans and simultaneous publication in the Journal of the American Medical Association, a surprising revelation occurred to cardiologists who treat heart failure: fluid loss means little to overall survival.

For those unfamiliar with the EVEREST trial, it tested the effectiveness of a vasopressin inhibitor, tolvaptan, at reducing fluid retention in heart failure as a means to improve cardiovascular mortality. Vasopressin’s (also called “anti-diuretic hormone”) action in the kidney is to retain free water in the distal collecting tubules of the nephron in the kidney. It is alcohol’s inhibition of vasopressin that causes a brisk diuresis that contributes to the post-drinking hang-over and dehydration. Ah, enough about my college days…

Anyway, the drug tolvaptan also inhibits vasopressin, and permits excretion of increased free water (as evidenced by the sustained volume loss and elevation of serum salt (sodium) levels in this study). Unfortunately, these beneficial effects had no effect on all-cause or cardiovascular mortality after two years of follow-up in the trial.

What struck me was the high incidence of cardiovascular mortality in this heart failure patient population (NYHA Class III and IV): an incidence of about 20% - even in spite of aggressive therapy with beta blockers (70.2% of patients), angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors (84.2%), and diuretics (96.8%).

It seems we have a long way to go to improve mortality in this population.

Which then begs the question: in light of the improvements in mortality in severe heart failure documented in the MIRACLE, COMPANION, CARE-HF and SCD-HeFT trials, why is there no mention of device-based heart failure therapies in this trial? Were these devices implanted in these patients? If so, in whom?

Perhaps if these device therapies were deployed earlier in the course of treatment in this severe heart failure population, we could better impact this abysmal mortality rate.

-Wes