All concepts, explanations, trials, and studies have been
re-written in plain English and may contain errors. I am
not a doctor
-----------------------------------------------------------

NOTE: You can make the print bigger with the font button
on your browser! (It's usually a big "A")

-----------------------------------------------------------

Jon's note: This was not an actual trial designed to study
	this exact question - this is a study of already-
	existing data from hospital records. While I
	have concerns about the accuracy of this kind
	of study, where all possible other causes for
	the outcome are supposedly "excluded", it is
	information to consider. There is a "chicken or
	the egg" factor as well. Did higher diuretic dose
	increase risk of death or were sicker, higher risk
	patients the ones most likely taking higher
	diuretic doses anyway? Can all those factors be
	statistically juggled with real accuracy? I don't
	know - decide for yourself. 

-----------------------------------------------------------

Risk of Death Higher with Higher Diuretic Dose in CHF

July 19, 2006 - Researchers studied whether diuretic dose
is linked to CHF risk of death (prognosis). The study
included 1,354 patients with advanced systolic HF
referred to one medical center between 1985 and 2004.
Patients were divided into 4 groups (quartiles) by
diuretic dose taken :

1)  daily loop diuretic dose: 0 to 40 mg
2)  41 to 80 mg
3)  81 to 160 mg
4)  more than 160 mg daily.

Patients were 76% male, with an average age of 53 years
and average EF of 24%. Average daily diuretic dose for all
patients together was 107 mg. Groups were similar in sex,
obesity, ischemic cause of CHF, history of high blood
pressure and spironolactone use.
	The highest quartile did have lower EF, lower
blood sodium and lower hemoglobin levels, and also had
reduced kidney function.
	The lower the diuretic dose, the lower the risk
of death :

1)  83% survival
2)  81% survival
3)  68% survival
4)  53% survivial

So patients in quartile number 4 were roughly 4 times as
likely to die as patients in quartile number 1. Even after
extensive "co-variate adjustment" to eliminate other
factors that might influence risk of death, lower diuretic
dose still predicted lower risk of death.
	Things excluded by "co-variate adjustment"
included age, sex, ischemic cause of CHF, EF, obesity,
PCWP, peak oxygen consumption, beta-blocker use, ACE
inhibitor or ARB use, digoxin use, statin drug use, blood
sodium level, kidney function, hemoglobin, cholesterol,
systolic blood pressure, and smoking history.
	These researchers believe that higher loop
diuretic dosages identify CHF patients at particularly high
risk for death.
	One of the researchers (Fonarow) said, "Loop
diuretics especially at higher doses further activate
neurohumoral systems in CHFers. ... Activation of these
neurohumoral systems is well known to increase the risk
of death in patients with heart failure. Loop diuretics,
especially at higher doses, can also contribute to worsened
kidney function and electrolyte abnormalities."
	Dr. Fonarow also said that, "... loop diuretics
should be used at the lowest dose possible to relieve
congestion. Some physicians (in the study) favored using
higher than necessary doses of loop diuretics (to keep
patients 'dry'). This study suggests that this practice should
be avoided."

Jon's note: The next question would be, "Do loop diuretics
actually cause harm?" If so, is it the drug itself or are
doctors not using them properly in CHF patients for best
outcomes? Will any trials be done on this? I guess no, but
we can hope.

Title:      Relation of loop diuretic dose to mortality in
              advanced heart failure.
Authors: Eshaghian S, Horwich TB, Fonarow GC.
Source:   Am J Cardiol. 2006 Jun 15;97(12):1759-64. Epub 2006 Apr 27.
Source:   Reuters Health
PMID:   16765130.