METHYLXANTHINE DRUG-THERAPY IN CHRONIC HEART-FAILURE ASSOCIATED WITH HYPOXEMIA - DOUBLE-BLIND PLACEBO-CONTROLLED CLINICAL-TRIAL OF DOXOFYLLINE VERSUS THEOPHYLLINE AND BAMIFYLLINE
Fl. Dini et al., METHYLXANTHINE DRUG-THERAPY IN CHRONIC HEART-FAILURE ASSOCIATED WITH HYPOXEMIA - DOUBLE-BLIND PLACEBO-CONTROLLED CLINICAL-TRIAL OF DOXOFYLLINE VERSUS THEOPHYLLINE AND BAMIFYLLINE, International journal of clinical pharmacology research, 13(6), 1993, pp. 305-316
The effects of the methylxanthine drugs doxofylline, theophylline and
bamifylline were investigated on the basis of clinical and gasometric
parameters in hypoxic patients with chronic heart failure. A parallel,
double-blind, randomized study was conducted in 48 in-patients with N
YHA II-IV chronic heart failure with normo- or hypercapnic hypoxaemia.
They were divided into three groups and then submitted to a 4-day run
-in with placebo. Either doxofylline 800 mg b.i.d., theophylline slow-
release 400 mg b.i.d. or bamifylline 1200 mg b.i.d. were administered
orally in each group of 16 patients for 10 days. Exercise capacity was
estimated through NYHA class,modification. Gasometric determinations,
including arterial oxygen tension (PaO2), carbon dioxide tension (PaC
O2) and oxygen saturation (SaO2), were measured from arterial blood sa
mples at the time of enrollment (T-4), at the onset of xanthine therap
y (TO) and at the end of the trial (T9). After 10 days' treatment, the
NYHA class was found to be diminished in 50% of the doxofylline group
, 50% of the bamifylline group and 44% of the theophylline group. PaO2
showed a > 15% increase in 75% of the doxofylline group, 56% of the t
heophylline group and 43% of the bamifylline group (responders). In al
l three groups the responders presented a highly significant enhanceme
nt in PaO2 and SaO2 (p < 0.01 TO vs T9). Doxofylline exhibited the hig
hest percent increase in PaO2 and SaO2 with respect to T0. The effects
on cardiac rhythm showed a progressive heart-rate reduction in the do
xofylline group, whereas patients receiving theophylline presented an
increased rate of beating. In conclusion, the use of methylxanthines i
n patients with chronic heart failure seems to be particularly effecti
ve especially when a significant ventilatory dysfunction is present. D
oxofylline appears to be specially useful because of its ability not t
o interfere with cardiac rhythm.