Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition.
BACKGROUND
Organic nitrates are widely used in the treatment of chronic heart failure (CHF). No information, however, is available regarding their effect in patients already treated with ACE inhibitors.


RESULTS
In a randomized, double-blind, crossover design, we studied the effects of high-dose (50 to 100 mg) transdermal nitroglycerin (NTG) and placebo given daily for 12 hours in 29 patients with CHF (NYHA functional classes II to III). Exercise time (4 hours after patch application) showed a progressive improvement during NTG administration, with an increase of 38+/-35 seconds (9+/-7%) at the end of the first month (P=NS), 76+/-28 seconds (16+/-6%) at the end of the second month (P=0.01), and 117+/-34 seconds (27+/-6%) at the end of the third month (P=0.003). No significant change was seen during placebo administration (12+/-20, 5+/-26, and 19+/-28 seconds, all P=NS). Exercise time 8 hours after NTG application measured at 3 months was also significantly longer, with a difference of 87+/-28 seconds (P=0.006), but not with placebo (23+/-36 seconds, P=0.53). Assessment of quality of life and need for additional diuretics or hospitalizations for CHF failed to demonstrate a significant difference between the 2 treatment periods. In contrast, NTG decreased left ventricular end-diastolic (-2.1+/-0.1%, P<0.05) and end-systolic (-3.2+/-1.3%, P<0.05) dimensions and augmented LV fractional shortening (24.7+/-10.5%, P<0.03). The effect of placebo on these parameters was not statistically significant.


CONCLUSIONS
High-dose nitrate therapy significantly improves exercise tolerance and left ventricular size and systolic function in patients with chronic, mild to moderate CHF already treated with ACE inhibitors. These findings support the role of organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic CHF.
Elkayam
U
U
Heart Failure Program, Division of Cardiology, Department of Medicine, University of Southern California School of Medicine, Los Angeles, Calif. 90033, USA. elkayam@hsc.usc.edu
Johnson
J V
JV
Shotan
A
A
Bokhari
S
S
Solodky
A
A
Canetti
M
M
Wani
O R
OR
Karaalp
I S
IS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002303:Cardiac Output, Low / Q000188:drug therapy*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004452:Echocardiography; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016037:Single-Blind Method; D013997:Time Factors; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D005996:Nitroglycerin