Sunday, March 25, 2007

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.


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