Beneficial effects of angiotensin-converting enzyme inhibitor and nitrate association on left ventricular remodeling in patients with large acute myocardial infarction: the Delapril Remodeling after Acute Myocardial Infarction (DRAMI) trial.
BACKGROUND
In the large-scale trial, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-3 (GISSI-3), patients receiving the combination of lisinopril and glyceryl trinitrate benefited most from experimental therapy. Therefore, a multicenter, randomized, double-blind study, Delapril Remodeling After Acute Myocardial Infarction (DRAMI), was designed to assess (1) the possible additive beneficial effect on left ventricular remodeling of nitrates when combined with an angiotensin-converting enzyme inhibitor (ACEI), and (2) the tolerability of a new ACEI, delapril, in respect to lisinopril in patients with large myocardial infarction (MI).


METHODS
A total of 177 patients were randomized to receive delapril plus isosorbide-5-mononitrate (IS5MN) placebo, delapril plus IS5MN, lisinopril plus IS5MN placebo, or lisinopril plus IS5MN starting within the first 36 hours after the onset of symptoms and continuing for 3 months.


RESULTS
More than 80% of the patients showed extensive ST-segment changes and 36.7% had signs or symptoms of heart failure during the first 36 hours. Over 3 months, IS5MN reduced, by 76%, the increase in LVEDV (17.4 +/- 5.0 mL placebo vs 4.2 +/- 4.4 mL IS5MN, P =.0439), reversed the increase in LVESV (7.5 +/- 3.9 mL placebo vs -5.5 +/- 2.9 mL IS5MN, P =.0052), and increased the recovery of LVEF (1.9% +/- 1.3% placebo vs 6.7% +/- 1.2% IS5MN, P =.0119). Overall, 3-month mortality was 10.2%; the most frequent clinical events were new episodes of severe heart failure (18.1%), persistent hypotension (10.7%), and post-MI angina (18.1%), with no differences between treatment groups.


CONCLUSIONS
Administration for 3 months of IS5MN combined with an ACEI, both started within 36 hours from the onset of symptoms, was safe and effective in reducing LV dilation and dysfunction after MI. The 2 ACEIs, delapril and lisinopril, appeared to be equally well tolerated.
Latini
Roberto
R
Istituto Mario Negri, Milano, Italy. latini@marionegri.it
Staszewsky
Lidia
L
Maggioni
Aldo P
AP
Marino
Paolo
P
Hernandez-Bernal
Francisco
F
Tognoni
Gianni
G
Labarta
Violeta
V
Gramenzi
Silvana
S
Bianchi
Federico
F
Sarcina
Giuseppe
G
Cremonesi
Giovanni
G
Nicolosi
Gian Luigi
GL
Geraci
Enrico
E
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017706:Lisinopril / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015990:Placebo Effect; D013223:Statistics as Topic; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; D014665:Vasodilator Agents; D017706:Lisinopril; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; C047759:delapril