Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors.
BACKGROUND
Pulmonary function abnormalities participate in causing exercise disability in patients with congestive heart failure (CHF). Impaired pulmonary gas transfer is one of these abnormalities. Angiotensin-converting enzyme (ACE) inhibitors improve diffusion for carbon monoxide and exercise capacity, an effect that is seemingly mediated through prostaglandin activation because it is inhibited by cyclooxygenase blockade with aspirin. This suggests the possibility that aspirin may disturb the pulmonary function and exercise ability in CHF, at least in those patients who are taking ACE inhibitors. This study was aimed at probing this hypothesis.


METHODS
A dose of 325 mg aspirin was given daily for 8 weeks to 26 consecutive patients with primary dilated cardiomyopathy (New York Heart Association class II or III) whose current outpatient antifailure therapy included (group 1, 18 cases) or did not include (group 2, 8 cases) an ACE inhibitor in addition to digoxin and furosemide. During the study ACE inhibition was continued in group 1 by giving enalapril 20 mg daily.


RESULTS
Tests repeated at 8 weeks proved that aspirin was deleterious in group 1. Compared with run-in, rest carbon dioxide, peak exercise oxygen uptake (peak VO(2 )), and tidal volume levels were diminished in this group; the ratio of exercise minute ventilation to carbon dioxide production (VE/VCO(2)) was augmented and its variations were inversely related to those of peak VO(2). Similar results were not observed in group 2; however, once this part of the study was completed and enalapril was included in the current therapeutic regimen, an inhibitory effect of aspirin on carbon dioxide, peak VO(2), peak tidal volume, and VE/VCO(2) at 1 L levels became evident and was similar to that observed in group 1.


CONCLUSIONS
Aspirin does not affect ventilation efficiency and peak VO(2 ) in patients with CHF not taking ACE inhibitors, but it worsens the pulmonary diffusion for carbon monoxide, VO(2 ), and the ventilatory response to exercise in the presence of ACE inhibition. This may be relevant in patients with CHF from ischemic heart disease. Whether the same may be true of smaller aspirin doses was not investigated in this study.
Guazzi
M
M
Istituto di Cardiologie dellUniversità degli Studi, Centro di Studio per le Ricerhe Cardiovascolari del Consiglio Nazionale delle Ricerche, Fondazione "Monzine", IRCCS, Milan, Italy. cardguaz@imiucca.csi.unimi.it
Pontone
G
G
Agostoni
P
P
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004656:Enalapril / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D013147:Spirometry
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D004656:Enalapril; D001241:Aspirin