The Effect of the Angiotensin

7/28/2019 The Effect of the Angiotensin

1/16

The Effect of the Angiotensin-ConvertingEnzymeInhibitor Zofenopril on Mortality and Morbidity after

Anterior Myocardial Infarction

Ettore Ambrosioni, M.D., Claudio Borghi, M.D., Bruno Magnani, M.D., for TheSurvival of Myocardial Infarction Long-Term Evaluation (SMILE) StudyInvestigators

ABSTRACT

BackgroundLeft ventricular dilatation and neuroendocrine activationare commonafter acute anterior myocardial infarction. Long-termtreatment with an angiotensin-convertingenzyme (ACE)inhibitor may improve outcome by attenuating theseprocesses.We investigated whether the ACE inhibitor zofenopril, administeredfor sixweeks after anterior myocardial infarction, could improveboth short-term and long-

term outcome.

Methods A total of 1556 patients were enrolled within 24 hoursafter the onset ofsymptoms of acute anterior myocardial infarction,and they were randomly assignedin a double-blind fashion toreceive either placebo (784 patients) or zofenopril (772patients)for six weeks. At this time we assessed the incidence of death or severecongestive heart failure. The patients were reexaminedafter one year to assesssurvival.

Results The incidence of death or severe congestive heart failureat six weeks wassignificantly reduced in the zofenopril group(55 patients, 7.1 percent), as comparedwith the placebo group(83 patients, 10.6 percent); the cumulative reduction in the

risk of death or severe congestive heart failure was 34 percent(95 percentconfidence interval, 8 to 54 percent; P = 0.018).The reduction in risk was 46 percent(95 percent confidenceinterval, 11 to 71 percent; P = 0.018) for severe congestive

heart failure and 25 percent (95 percent confidence interval,-11 to 60 percent; P =0.19) for death. After one year of observation,the mortality rate was significantlylower in the zofenoprilgroup (10.0 percent) than in the placebo group (14.1 percent);

the reduction in risk was 29 percent (95 percent confidenceinterval, 6 to 51 percent;P = 0.011).

Conclusions Treatment with zofenopril significantly improved

both short-term andlong-term outcome when this drug was startedwithin 24 hours after the onset ofacute anterior myocardialinfarction and continued for six weeks.

The outcome of patients with acute myocardial infarction hasbeen improved by the early

administration of drugs such as thrombolyticagents, beta-blockers, and aspirin.1,2,3,4,5The use

of angiotensin-convertingenzyme(ACE) inhibitors has also been reported to be beneficial in

patients after acute myocardial infarction,6,7and the benefitseems to be greatest in patients

with congestive heart failure8or asymptomatic ventricular dysfunction.9,10Ventricular

dysfunctionis an important prognostic indicator after myocardial infarction.11,12ACE

inhibitors may function in part by affecting the process

of ventricular remodeling.13

Recently,the third study by theGruppo Italiano per lo Studio della Sopravvivenza nell'Infarto
http://content.nejm.org/cgi/content/full/332/2/80#R1http://content.nejm.org/cgi/content/full/332/2/80#R1http://content.nejm.org/cgi/content/full/332/2/80#R2http://content.nejm.org/cgi/content/full/332/2/80#R2http://content.nejm.org/cgi/content/full/332/2/80#R3http://content.nejm.org/cgi/content/full/332/2/80#R3http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R5http://content.nejm.org/cgi/content/full/332/2/80#R5http://content.nejm.org/cgi/content/full/332/2/80#R5http://content.nejm.org/cgi/content/full/332/2/80#R6http://content.nejm.org/cgi/content/full/332/2/80#R6http://content.nejm.org/cgi/content/full/332/2/80#R7http://content.nejm.org/cgi/content/full/332/2/80#R7http://content.nejm.org/cgi/content/full/332/2/80#R7http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R9http://content.nejm.org/cgi/content/full/332/2/80#R9http://content.nejm.org/cgi/content/full/332/2/80#R10http://content.nejm.org/cgi/content/full/332/2/80#R10http://content.nejm.org/cgi/content/full/332/2/80#R10http://content.nejm.org/cgi/content/full/332/2/80#R11http://content.nejm.org/cgi/content/full/332/2/80#R11http://content.nejm.org/cgi/content/full/332/2/80#R12http://content.nejm.org/cgi/content/full/332/2/80#R12http://content.nejm.org/cgi/content/full/332/2/80#R12http://content.nejm.org/cgi/content/full/332/2/80#R13http://content.nejm.org/cgi/content/full/332/2/80#R13http://content.nejm.org/cgi/content/full/332/2/80#R13http://content.nejm.org/cgi/content/full/332/2/80#R13http://content.nejm.org/cgi/content/full/332/2/80#R12http://content.nejm.org/cgi/content/full/332/2/80#R11http://content.nejm.org/cgi/content/full/332/2/80#R10http://content.nejm.org/cgi/content/full/332/2/80#R9http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R7http://content.nejm.org/cgi/content/full/332/2/80#R6http://content.nejm.org/cgi/content/full/332/2/80#R5http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R3http://content.nejm.org/cgi/content/full/332/2/80#R2http://content.nejm.org/cgi/content/full/332/2/80#R1


2/16

Miocardico (GISSI-3)14showed that early treatment with an ACEinhibitor reduced mortality

at six weeks when given to a large,unselected population of patients with myocardial

infarction.These results have been supported by preliminary data from thefourth

International Study of Infarct Survival15but not bythe results of the second Cooperative New

Scandinavian EnalaprilSurvival Study.16We wanted to address the question of the efficacy of

an ACE inhibitor in patients at high risk for death and congestive

heart failure. We chosepatients with anterior myocardial infarctions,because they often have a substantial degree of

ventriculardysfunction17and a worse outcome in terms of these events.18

Accordingly, the Survival of Myocardial Infarction Long-TermEvaluation trial was planned

to test the hypothesis that oral administration of an ACE inhibitor, zofenopril, to patientswith

acute anterior myocardial infarction who were not undergoingthrombolysis would improve

their clinical outcome by reducingthe incidence of major cardiovascular events. We were

particularlyinterested in whether a short (six-week) course of drug therapywould have a

sustained beneficial effect over the subsequent year.

Methods

Organization of the Study

The study was a randomized, double-blind, placebo-controlledtrial involving 1556 patients

with acute anterior myocardialinfarctions who were not eligible for thrombolytic therapy and

who were enrolled at 154 centers in Italy (listed in the Appendix).The study was conducted

in accordance with the Declaration ofHelsinki (1989) and was approved by the institutional

reviewboard of the University of Bologna as well as by the local ethicscommittees when

required. All the patients provided informedconsent.

Recruitment of Patients

The enrollment phase of the trial began in January 1991 andended in November 1992.

Patients of either sex who were 18 to80 years of age were eligible if they presented to the

intensivecare unit within 24 hours of the onset of chest pain typicallyassociated with

electrocardiographic signs of myocardial infarctionof the anterior wall and if they were not

eligible for thrombolytictherapy because of late admission to the intensive care unit or

contraindications to systemic fibrinolysis.4,8

Acute anterior myocardial infarction was considered to have occurred if the

electrocardiogram showed progressive changes

in the ST segments or T waves in at least twocontiguous precordialleads with or without new abnormal Q waves. Patients were excluded

from the study if they were in cardiogenic shock (Killip class 4) on admission, had a systolic

blood pressure below 100 mmHg (measured with the patient supine) on admission, had a

serumcreatinine concentration above 2.5 mg per deciliter (221 mol per liter), had a history

of congestive heart failure, werebeing treated with ACE inhibitors, had contraindications to

the use of ACE inhibitors, or were unable or unwilling to giveinformed consent. All

potentially eligible patients receivedstandard therapy including analgesic agents, beta-

blockers,nitrates, calcium antagonists, aspirin, inotropic drugs, diureticagents, and

anticoagulants as indicated.

Randomization, Titration, and Follow-Up
http://content.nejm.org/cgi/content/full/332/2/80#R14http://content.nejm.org/cgi/content/full/332/2/80#R14http://content.nejm.org/cgi/content/full/332/2/80#R14http://content.nejm.org/cgi/content/full/332/2/80#R15http://content.nejm.org/cgi/content/full/332/2/80#R15http://content.nejm.org/cgi/content/full/332/2/80#R15http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R17http://content.nejm.org/cgi/content/full/332/2/80#R17http://content.nejm.org/cgi/content/full/332/2/80#R18http://content.nejm.org/cgi/content/full/332/2/80#R18http://content.nejm.org/cgi/content/full/332/2/80#R18http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R8http://content.nejm.org/cgi/content/full/332/2/80#R4http://content.nejm.org/cgi/content/full/332/2/80#R18http://content.nejm.org/cgi/content/full/332/2/80#R17http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R15http://content.nejm.org/cgi/content/full/332/2/80#R14


3/16

The study drug, zofenopril (Bristol-Myers Squibb, Princeton,N.J.), is a new short-acting

ACE inhibitor that contains a sulfhydrylgroup and is an analogue of captopril; its

characteristics havebeen extensively reviewed.19,20,21,22The patients were randomlyassigned

with the use of fixed blocks to receive zofenopril or placebo, and the details of the

randomization procedureshave been published elsewhere.23The initial dose of medication

was 7.5 mg. The dose was repeated after 12 hours and progressively

doubledas long assystolic blood pressure remainedabove 100 mm Hg and there were no signs or symptoms of

hypotensionuntil the final target dose of 30 mg twice daily was reached. Patients who

were unable to tolerate the dose of 7.5mg were withdrawn from the study but included in the

intention-to-treatanalysis. Patients were seen while they were in the hospital (7 to 15 days),

after 4 weeks, and at the end of the treatment period (mean, 6 weeks 3 days), during which

time theycould be treated with any other drug except ACE inhibitors.On completion of the

6-week double-blind period, the patientsstopped taking the study medications but continued

treatmentwith their other medications for a mean of 484 additionalweeks, at which time

vital status was blindly evaluated. Vital status was determined by means of a questionnaire

for 1249 patientsand by family members, medical personnel, and registry offices for 307

patients.

End Points

The primary end point was the occurrence of death or severe congestive heart failure during

the treatment period. The twowere tabulated as a single event, according to which one

occurredfirst.

Patients were considered to have severe congestive heart failureif after randomization they

had at least three of the following:third heart sound, bilateral pulmonary rales, radiologic

evidenceof pulmonary congestion (a score above grade II on the scale of Madsen et al.),24or

peripheral edema, despite the concomitantadministration of digoxin, diuretics, and

vasodilators otherthan ACE inhibitors and necessitating open-label treatment with an ACE

inhibitor. Clinical signs of mild-to-moderate congestiveheart failure during follow-up were

categorized according tothe New York Heart Association classification (I through IV).

The causes of death were classified by the principal investigators and reviewed by an end-

points committee acting on the basisof a blinded review. All deaths occurring during the trial

wereclassified as due to cardiac or noncardiac causes. Cardiac causesincluded progressive

heart failure, sudden death, recurrentmyocardial infarction, and cardiac rupture. Noncardiac

causesincluded cerebrovascular events, pulmonary embolism, and nonvascularcauses.

Progressive heart failure was classified on the basis

of pump failure and the occurrence ofcardiogenic shock. Suddendeath was defined as sudden, unexpected death occurring within

one hour after the onset of new symptoms.

Secondary prospectively defined end points for the study includedthe effect of six weeks of

treatment on the occurrence of clinicalsigns of mild-to-moderate congestive heart failure,

nonfatalrecurrent myocardial infarction, and angina, and cumulativeone-year mortality.

Statistical Analysis

The study was planned to include 1500 patients on the basisof an expected mortality rate of

12 percent at six weeks and

an expected rate of severe congestive heart failure of 5 percent

inthe placebo group, a 30 percent reduction in the occurrenceof death or severe congestive
http://content.nejm.org/cgi/content/full/332/2/80#R19http://content.nejm.org/cgi/content/full/332/2/80#R19http://content.nejm.org/cgi/content/full/332/2/80#R20http://content.nejm.org/cgi/content/full/332/2/80#R20http://content.nejm.org/cgi/content/full/332/2/80#R21http://content.nejm.org/cgi/content/full/332/2/80#R21http://content.nejm.org/cgi/content/full/332/2/80#R22http://content.nejm.org/cgi/content/full/332/2/80#R22http://content.nejm.org/cgi/content/full/332/2/80#R22http://content.nejm.org/cgi/content/full/332/2/80#R23http://content.nejm.org/cgi/content/full/332/2/80#R23http://content.nejm.org/cgi/content/full/332/2/80#R23http://content.nejm.org/cgi/content/full/332/2/80#R24http://content.nejm.org/cgi/content/full/332/2/80#R24http://content.nejm.org/cgi/content/full/332/2/80#R24http://content.nejm.org/cgi/content/full/332/2/80#R24http://content.nejm.org/cgi/content/full/332/2/80#R23http://content.nejm.org/cgi/content/full/332/2/80#R22http://content.nejm.org/cgi/content/full/332/2/80#R21http://content.nejm.org/cgi/content/full/332/2/80#R20http://content.nejm.org/cgi/content/full/332/2/80#R19


4/16

heart failure in the zofenoprilgroup as compared with the placebo group, a dropout rate of1

percent, a statistical power of at least 80 percent, and asignificance level of 5 percent (two-

tailed test). The resultswere analyzed by an independent data-coordinating center. Noformal

interim analysis was undertaken during the course ofthe trial. The cumulative prevalence of

death or severe congestiveheart failure at six weeks was the main outcome variable

compared

in the two treatment groups. All analyses were performed on

an intention-to-treatbasis, and all P values are two-tailed.For the comparison of the zofenopril and placebo

groups withrespect to end points, risk reductions and corresponding 95percent confidence

intervals were determined. The chi-squaretest with the MantelHaenszel extension was used

for thecomparisons between the two groups. Follow-up data collectedafter one year were

analyzed according to the original groupassignment. Life-table curves were calculated and

the survivalanalysis was performed with the use of the LeeDesu statisticsfor group

comparisons.

Results

From January 1991 to November 1992, a total of 20,261 patientswere admitted to the 154

coronary care units in the study; 1556patients were enrolled in the trial and randomly

assigned toone of the treatment groups. The diagnosis of acute myocardial infarction was

confirmed in 96.1 percent of the patients whounderwent randomization; 3.6 percent had

acute coronary syndromes,and the remaining 0.3 percent were given other diagnoses. The

base-line clinical characteristics of the two groups of patientsare shown inTable 1.

View this table:[in this window]

[in a new

window]

Table 1. Characteristics of the Patients at Base Line, According to

Treatment Group.

Primary Outcome Measures

During the six weeks of treatment, death or severe congestive heart failure occurred in 83 of

the 784 patients in the placebogroup (10.6 percent) and in 55 of the 772 patients in the

zofenoprilgroup (7.1 percent) (Figure 1); the reduction in the risk ofa major cardiovascular

event as defined above was 34 percent(95 percent confidence interval, 8 to 54 percent; P =

0.018).The reduction in risk was mainly attributable to a decrease in the incidence of severe

congestive heart failure requiringopen-label treatment with an ACE inhibitor, whereas therelativecontribution of death was not statistically significant (Table 2).When we examined

the cumulative incidence of death fromall causes regardless of whether there was prior

congestiveheart failure, we found that there were 65 deaths in the placebogroup (8.3 percent)

as compared with 50 in the zofenopril group(6.5 percent) (Table 3). Thus, the reduction in

the risk ofdeath from all causes during the six-week treatment period was22 percent (95

percent confidence interval, -12 to 48 percent;P = 0.17) and was almost entirely due to the

reduction in cardiovascularmortality in the zofenopril group (reduction in risk, 22 percent;95

percent confidence interval, -8 to 53 percent; P = 0.08)(Table 3). There was also a marked

difference between the zofenoprilgroup and the placebo group in the number of patients who

diedwithin 24 hours after randomization (1 vs. 8 deaths). The numbersof deaths due to

noncardiac causes were similar in the two treatmentgroups (Table 3).
http://content.nejm.org/cgi/content/full/332/2/80#T1http://content.nejm.org/cgi/content/full/332/2/80#T1http://content.nejm.org/cgi/content/full/332/2/80#T1http://content.nejm.org/cgi/content/full/332/2/80/T1http://content.nejm.org/cgi/content/full/332/2/80/T1http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://content.nejm.org/cgi/content/full/332/2/80#F1http://content.nejm.org/cgi/content/full/332/2/80#F1http://content.nejm.org/cgi/content/full/332/2/80#F1http://content.nejm.org/cgi/content/full/332/2/80#T2http://content.nejm.org/cgi/content/full/332/2/80#T2http://content.nejm.org/cgi/content/full/332/2/80#T2http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T3http://content.nejm.org/cgi/content/full/332/2/80#T2http://content.nejm.org/cgi/content/full/332/2/80#F1http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://content.nejm.org/cgi/content/full/332/2/80/T1http://content.nejm.org/cgi/content/full/332/2/80#T1


5/16

View larger version (2K):

[in this window]

[in a new window]

Figure 1. Incidence of Death or Severe Congestive Heart

Failure during Six Weeks of Treatment with Zofenopril or

Placebo in Patients with Acute Myocardial Infarction.

View this

table:[in this

window]

[in a new

window]

Table 2. Incidence of Severe Congestive Heart Failure or Death as the

Combined Primary End Point of the Study.

View this

table:[in this

window]

[in a new

window]

Table 3. Cumulative Incidence of Death from All Causes after Six Weeks of

Treatment with Zofenopril or Placebo, Regardless of Whether There Was

Prior Congestive Heart Failure.

Secondary Outcome Measures

During the six weeks of treatment angina occurred in 153 patients (19.5 percent) in the

placebo group and in 128 patients (16.6percent) in the zofenopril group. Thus, the reduction

in riskwas 18 percent (95 percent confidence interval, -6 to 37; P = 0.08). After

randomization, 23 patients had at least one clinicallyreported nonfatal myocardial infarction

(12 patients in theplacebo group and 11 in the zofenopril group). A total of 75patients (9.6

percent) in the placebo group had clinical signsof mild-to-moderate congestive heart failure

after six weeks,as compared with 52 patients (6.7 percent) in the zofenoprilgroup, with a

reduction in risk of borderline statistical significance(reduction in risk, 29 percent; 95 percent

confidence interval,

-2 to 51; P = 0.054). The use of other medications during the

six-weektreatment period was comparable in the two groups withthe exception of the use of digoxin,
http://content.nejm.org/cgi/content/full/332/2/80/F1http://content.nejm.org/cgi/content/full/332/2/80/F1http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://content.nejm.org/cgi/content/full/332/2/80/T2http://content.nejm.org/cgi/content/full/332/2/80/T2http://content.nejm.org/cgi/content/full/332/2/80/T2http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://content.nejm.org/cgi/content/full/332/2/80/T3http://content.nejm.org/cgi/content/full/332/2/80/T3http://content.nejm.org/cgi/content/full/332/2/80/T3http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://content.nejm.org/cgi/content/full/332/2/80/F1http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://content.nejm.org/cgi/content/full/332/2/80/T3http://content.nejm.org/cgi/content/full/332/2/80/T3http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://content.nejm.org/cgi/content/full/332/2/80/T2http://content.nejm.org/cgi/content/full/332/2/80/T2http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://content.nejm.org/cgi/content/full/332/2/80/F1


6/16

which was given less oftento patients taking zofenopril than to patients taking placebo(5.8

percent vs. 8.4 percent, P = 0.041), a finding consistentwith the lower incidence of the

clinical manifestations of heartfailure in this group (data not shown).

The one-year mortality rates for all patients according to theiroriginal treatment assignments

are shown inFigure 2. Patients

who received zofenopril for six weeks were significantly more

likely to survive than patients given placebo. During the yearof observation 77 of 772

patients in the zofenopril group (10.0percent) died, as compared with 111 of 784 patients in

the placebogroup (14.1 percent), and this difference accounted for a significant reduction in

the risk of death (29 percent; 95 percent confidenceinterval, 6 to 51; P = 0.011). This

reduction in risk cannotbe explained by differences in the concomitant pharmacologicor

surgical treatment, which was ascertained for over 80 percentof the patients (Table 4).

View larger version (2K):

[in this window]

[in a new window]

Figure 2. Cumulative Mortality during One Year of

Follow-up among Patients with Acute Myocardial

Infarction Treated for Six Weeks with Zofenopril or

Placebo.

View this table:[in this window]

[in a new

window]

Table 4. Treatments Administered to the Patients during One Year of

Observation.

Analysis of Subgroups

The primary end point was assessed in subgroups defined on thebasis of characteristics or

treatments known to influence survivalafter myocardial infarction (Table 5). The beneficial

effectof zofenopril therapy was apparent in patients with a previousmyocardial infarction

and in those concomitantly treated withcalcium-channel blockers and nitrates during

hospitalization.

View this

table:[in this

window][in a new

Table 5. Effects of Zofenopril on the Primary End Point (Death or Severe

Congestive Heart Failure) in Subgroups Defined on the Basis of Characteristics

or Pharmacologic Treatments Known to Influence the Outcome in Patients with

Myocardial Infarction.
http://content.nejm.org/cgi/content/full/332/2/80#F2http://content.nejm.org/cgi/content/full/332/2/80#F2http://content.nejm.org/cgi/content/full/332/2/80#F2http://content.nejm.org/cgi/content/full/332/2/80#T4http://content.nejm.org/cgi/content/full/332/2/80#T4http://content.nejm.org/cgi/content/full/332/2/80#T4http://content.nejm.org/cgi/content/full/332/2/80/F2http://content.nejm.org/cgi/content/full/332/2/80/F2http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://content.nejm.org/cgi/content/full/332/2/80/T4http://content.nejm.org/cgi/content/full/332/2/80/T4http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://content.nejm.org/cgi/content/full/332/2/80#T5http://content.nejm.org/cgi/content/full/332/2/80#T5http://content.nejm.org/cgi/content/full/332/2/80#T5http://content.nejm.org/cgi/content/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80/T5http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80/F2http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80/T5http://content.nejm.org/cgi/content/full/332/2/80#T5http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://content.nejm.org/cgi/content/full/332/2/80/T4http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://content.nejm.org/cgi/content/full/332/2/80/F2http://content.nejm.org/cgi/content/full/332/2/80#T4http://content.nejm.org/cgi/content/full/332/2/80#F2


7/16

window]

Blood-Pressure Profile

The overall prevalence of hypotension, conservatively definedas a systolic blood pressure

below 100 mm Hg at any time duringthe study, was significantly higher in the zofenopril

group(132 patients, 17.1 percent) than in the placebo group (70 patients,8.9 percent,

P


8/16

any beneficial effect of early treatment withACE inhibitors.16We did not use the intravenous

route of administration.

Interestingly, the beneficial effect of short-term treatmentwith zofenopril was maintained

over time, as reflected by theimproved survival at one year. These data raise an important

issue concerning the ability of a short course of therapy to

improve long-term survival inpatients with acute myocardialinfarction. The mechanism of the persistent benefit even after

therapy had been discontinued remains to be sorted out. Othershave shown that early

treatment with an ACE inhibitor can improveleft ventricular function after myocardial

infarction.32

The current data add to a growing body of evidence supportingthe use of an ACE inhibitor

such as zofenopril early in thecourse of acute anterior myocardial infarction. We suggest that

the early administration of ACE inhibitors in patients with myocardial infarction can be

considered a reasonable strategyin high-risk subgroups, especially in patients with large

anteriormyocardial infarction.

http://content.nejm.org/cgi/content/full/332/2/80
http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R16http://content.nejm.org/cgi/content/full/332/2/80#R32http://content.nejm.org/cgi/content/full/332/2/80#R32http://content.nejm.org/cgi/content/full/332/2/80#R32http://content.nejm.org/cgi/content/full/332/2/80#R32http://content.nejm.org/cgi/content/full/332/2/80#R16


9/16

Efek dari Angiotensin-Converting-Enzyme InhibitorZofenopril pada Angka Kematian dan Kesakitan

setelah Anterior Myocardial Infarction

Ettore Ambrosioni, MD, Claudio Borghi, MD, Bruno Magnani, MD, The Survivalof Myocardial Infarction Long-Term Evaluation (SMILE) Studi Penyidik

ABSTRAK

Latar BelakangWaktu ventrikel dilatasi dan neuroendokrin aktivasi umum setelahinfark miokard anterior akut. Jangka panjang pengobatan dengan angiotensin-converting-enzyme (ACE) inhibitor dapat memperbaiki hasil oleh pelemahan prosesini. Kami menyelidiki apakah ACE zofenopril, dikelola selama enam minggu setelahinfark miokard anterior, dapat meningkatkan baik jangka pendek dan hasil jangka

panjang.

Metode Sebanyak 1556 pasien terdaftar dalam waktu 24 jam setelah timbul gejalaakut infark miokard anterior, dan mereka secara acak dalam double-blind fashionsampai menerima placebo (784 pasien) atau zofenopril (772 pasien) selama enamminggu. Pada saat ini kami menilai insiden kematian atau gagal jantung kongestifberat. Para pasien reexamined setelah satu tahun untuk menilai kelangsunganhidup.

Hasilkejadian kematian atau gagal jantung kongestif berat pada enam mingguberkurang secara signifikan dalam grup zofenopril (55 pasien, 7.1 persen),dibandingkan dengan kelompok plasebo (83 pasien, 10,6 persen); pengurangankumulatif dalam risiko kematian atau gagal jantung kongestif berat adalah 34 persen(95 persen confidence interval, 8-54 persen; P = 0,018). Pengurangan risiko adalah46 persen (95 persen confidence Interval, 11-71 persen; P = 0,018) untuk kongestifberat gagal jantung dan 25 persen (95 persen confidence interval, -11 Hingga 60persen; P = 0,19) untuk kematian. Setelah satu tahun observasi, tingkat kematiansecara signifikan lebih rendah di zofenopril kelompok (10,0 persen) dibandingkanpada kelompok plasebo (14,1 persen); pengurangan risiko adalah 29 persen (95persen confidence interval, 6 menjadi 51 persen; P = 0,011).

Kesimpulan Pengobatan dengan peningkatan secara signifikan zofenopril baikjangka pendek dan hasil jangka panjang ketika obat ini dimulai dalam waktu 24 jamsetelah onset akut miokard anterior miokard dan dilanjutkan selama enam minggu.

Hasil pasien dengan infark miokard akut telah ditingkatkan oleh administrasi awal seperti

obat-obatan trombolitik agen, beta-blocker, dan aspirin.1,2, 3, 4, 5Penggunaan angiotensin-

converting-enzim (ACE) inhibitor juga telah dilaporkan dapat bermanfaat dalam pasien

setelah infark miokard akut,6,7dan manfaat tampaknya paling besar pada pasien dengan

gagal jantung kongestif8 atau tanpa gejala disfungsi ventrikel.9,10ventrikel disfungsi

adalah indikator prognostik penting setelah infark miokard.11, 12 ACE inhibitor dapat

berfungsi sebagian dengan mempengaruhi proses ventrikel renovasi.13Baru-baru ini, studi

ketiga oleh Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico(GISSI-3)14menunjukkan bahwa perawatan dini dengan ACE inhibitor mengurangi angka
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R1#R1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R1#R1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R2#R2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R2#R2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R3#R3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R4#R4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R5#R5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R5#R5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R6#R6http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R6#R6http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R7#R7http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R7#R7http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R7#R7http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R9#R9http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R9#R9http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R10#R10http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R10#R10http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R10#R10http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R11#R11http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R11#R11http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R12#R12http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R12#R12http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R13#R13http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R13#R13http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R13#R13http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R14#R14http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R14#R14http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R14#R14http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R14#R14http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R13#R13http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R12#R12http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R11#R11http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R10#R10http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R9#R9http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R7#R7http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R6#R6http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R5#R5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R4#R4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R3#R3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R2#R2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R1#R1


10/16

kematian pada enam minggu ketika diberikan kepada seorang besar, populasi dipilih pasien

dengan infark miokard. Hasil ini telah didukung oleh data awal dari Studi Internasional

keempat infarct Survival15tetapi tidak oleh hasil kedua Skandinavia Baru enalapril Koperasi

Survival Study.16Kami ingin menjawab pertanyaan tentang kemanjuran ACE inhibitor dari

pada pasien risiko tinggi untuk kematian dan kongestif gagal jantung. Kami memilih pasien

dengan infark anterior infarctions, karena mereka sering memiliki tingkat substansialventrikular disfungsi17dan hasil yang lebih buruk dalam peristiwa ini.18

Oleh karena itu, Survival of Myocardial Infarction Long-Term Evaluasi Sidang ini

direncanakan untuk menguji hipotesis bahwa lisan administrasi inhibitor ACE, zofenopril,

untuk pasien dengan infark miokard anterior akut yang tidak menjalani trombolisis akan

meningkatkan hasil klinis dengan mengurangi insiden kejadian kardiovaskular utama. Kami

khususnya tertarik pada apakah pendek (enam minggu) terapi obat saja akan memiliki efek

menguntungkan yang berkelanjutan atas selanjutnya tahun.

Metode

Organisasi Kajian

Studi adalah acak, double blind, placebo-controlled pengadilan melibatkan 1.556 pasien

dengan miokard anterior akut infarctions yang tidak memenuhi syarat untuk terapi

trombolitik dan yang terdaftar di 154 pusat di Italia (tercantum dalam Lampiran). Studi ini

dilakukan sesuai dengan Deklarasi Helsinki (1989) dan telah disetujui oleh tinjauan

kelembagaan dewan dari University of Bologna dan juga oleh etika setempat komite bila

diperlukan. Semua pasien diberikan informasi persetujuan.

Perekrutan Pasien

The pendaftaran tahap persidangan dimulai pada Januari 1991 dan berakhir pada bulan

November 1992. Pasien dari kedua jenis kelamin yang adalah 18 untuk Usia 80 tahun

memenuhi syarat jika mereka dipresentasikan kepada intensif unit perawatan dalam waktu

24 jam setelah onset nyeri dada biasanya terkait dengan tanda-tanda electrocardiographic

infark miokard dari dinding anterior dan jika mereka tidak memenuhi syarat untuk

trombolitik terapi karena terlambat masuk ke unit perawatan intensif atau kontraindikasi

sistemik fibrinolisis.4, 8

Anterior akut infark miokard dianggap telah terjadi jika elektrokardiogram menunjukkan

perubahan progresif dalam segmen ST atau gelombang T dalam setidaknya dua bersebelahanprecordial memimpin dengan atau tanpa gelombang Q yang abnormal baru. Pasien

dikeluarkan dari penelitian jika mereka dalam kardiogenik syok (Killip kelas 4) pada

penerimaan, memiliki tekanan darah sistolik di bawah 100 mm Hg (diukur dengan pasien

terlentang) pada penerimaan, memiliki serum kreatinin konsentrasi di atas 2,5 mg per

desiliter (221 mol per liter), punya sejarah gagal jantung kongestif, yang dirawat dengan

ACE inhibitor, telah kontraindikasi untuk penggunaan ACE inhibitor, atau tidak mampu atau

tidak mau memberikan persetujuan. Semua berpotensi menerima pasien yang memenuhi

terapi standar termasuk agen analgesik, beta-blocker, nitrat, kalsium antagonis, aspirin, obat

inotropic, diuretik agen, dan antikoagulan seperti yang ditunjukkan.

Pengacakan, titrasi, dan Follow-Up
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R15#R15http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R15#R15http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R15#R15http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R17#R17http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R17#R17http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R17#R17http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R18#R18http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R18#R18http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R18#R18http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R4#R4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R4#R4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R8#R8http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R4#R4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R18#R18http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R17#R17http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R15#R15


11/16

Studi obat, zofenopril (Bristol-Myers Squibb, Princeton, NJ), adalah bertindak pendek baru

ACE inhibitor yang berisi sulfhidril kelompok dan merupakan analog kaptopril;

karakteristiknya telah ditinjau secara luas.19,20, 21, 22Para pasien secara acak ditetapkan

dengan menggunakan blok tetap menerima zofenopril atau plasebo, dan rincian prosedur

pengacakan telah diterbitkan di tempat lain.23dosis awal obat adalah 7,5 mg. Dosis ini

diulang setelah 12 jam dan progresif dua kali lipat - sepanjang tekanan darah sistolik tetap diatas 100 mm Hg dan tidak ada tanda-tanda atau gejala hipotensi - Sampai akhir dosis target

30 mg dua kali sehari itu tercapai. Pasien yang tidak mampu mentoleransi dosis 7,5 mg

ditarik dari studi tetapi dimasukkan dalam niat-ke-memperlakukan analisis. Pasien terlihat

ketika mereka berada di rumah sakit (7 sampai 15 hari), setelah 4 minggu, dan pada akhir

perawatan periode (berarti, 6 minggu 3 hari), selama itu mereka bisa diobati dengan obat

lain kecuali ACE inhibitor. Setelah menyelesaikan dari 6 minggu periode double blind,

pasien berhenti mengambil studi obat tapi terus perawatan dengan obat lain selama rata-rata

48 4 tambahan minggu, dan pada saat status penting secara membuta dievaluasi. Vital

status ditentukan dengan cara kuesioner untuk pasien 1249 dan oleh anggota keluarga,

petugas kesehatan, dan kantor registri untuk 307 pasien.

Akhir Points

Tujuan utama adalah terjadinya kematian atau parah gagal jantung kongestif selama masa

pengobatan. Kedua adalah tabel sebagai satu aktivitas, menurut mana yang terjadi pertama.

Pasien dianggap telah gagal jantung kongestif berat jika setelah pengacakan mereka

memiliki setidaknya tiga dari berikut ini: suara hati ketiga, bilateral rales paru, Radiologic

bukti kongesti paru (skor di atas kelas II pada skala dari Madsen et al.),24atau edema

perifer, meskipun seiring administrasi digoksin, diuretik, dan lain vasodilators dari ACE

inhibitor dan open-label yang memerlukan perawatan dengan ACE inhibitor. Tanda-tanda

klinis ringan hingga sedang kongestif gagal jantung selama masa tindak lanjut yang

dikelompokkan menurut New York Heart Association klasifikasi (I sampai IV).

Penyebab kematian diklasifikasikan oleh peneliti utama dan ditinjau oleh komite titik akhir

bertindak atas dasar review yang membutakan. Semua kematian yang terjadi selama

persidangan itu diklasifikasikan sebagai akibat jantung atau menyebabkan noncardiac.

Jantung menyebabkan termasuk gagal jantung progresif, tiba-tiba mati, berulang infark

miokard, dan jantung pecah. Noncardiac menyebabkan termasuk peristiwa serebrovaskular,

emboli paru, dan nonvascular penyebab. Progresif gagal jantung telah diklasifikasikan

berdasarkan dari pompa kegagalan dan terjadinya syok kardiogenik. Mendadak

didefinisikan sebagai kematian mendadak, kematian yang tak terduga terjadi di dalam satujam setelah timbul gejala baru.

Prospektif sekunder ditentukan titik akhir untuk penelitian termasuk efek dari enam minggu

pengobatan pada terjadinya klinis tanda-tanda ringan sampai sedang gagal jantung kongestif,

mematikan berulang infark miokard, dan angina, dan kumulatif satu tahun kematian.

Analisis Statistik

Studi ini direncanakan untuk memasukkan pasien 1500 berdasarkan dari angka kematian

yang diharapkan dari 12 persen pada enam minggu dan tingkat yang diharapkan gagal

jantung kongestif berat dari 5 persen di kelompok plasebo, 30 persen pengurangan terjadinyakematian atau gagal jantung kongestif yang parah di zofenopril kelompok dibandingkan
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R19#R19http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R19#R19http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R20#R20http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R20#R20http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R21#R21http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R22#R22http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R22#R22http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R23#R23http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R23#R23http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R23#R23http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R24#R24http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R24#R24http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R24#R24http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R24#R24http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R23#R23http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R22#R22http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R21#R21http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R20#R20http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R19#R19


12/16

dengan kelompok plasebo, yang putus sekolah tingkat 1 persen, kekuatan statistik minimal

80 persen, dan tingkat signifikansi 5 persen (dua-ekor). Hasil dianalisis oleh data

independen pusat koordinasi. Tidak analisis sementara formal dilakukan selama sidang.

Prevalensi kumulatif kematian atau kongestif berat gagal jantung pada enam minggu adalah

variabel hasil utama dibandingkan dalam dua kelompok perlakuan. Semua analisis yang

dilakukan pada niat-ke-memperlakukan dasar, dan semua nilai P dua sisi. Untukperbandingan zofenopril dan kelompok plasebo dengan Mengenai titik akhir, pengurangan

risiko dan berkorespondensi 95 persen confidence interval yang ditentukan. Chi-kuadrat

test dengan ekstensi Mantel-Haenszel digunakan untuk perbandingan antara dua kelompok.

Follow-up data yang dikumpulkan setelah satu tahun dianalisis menurut kelompok asli

tugas. Hidup-meja kurva dihitung dan kelangsungan hidup Analisis dilakukan dengan

penggunaan Lee-Desu statistik untuk perbandingan kelompok.

Hasil

Januari 1991 hingga November 1992, total 20.261 pasien yang mengakui 154 unit

perawatan koroner dalam penelitian; 1556 pasien yang terdaftar dalam persidangan dan

secara acak untuk salah satu dari kelompok perlakuan. Diagnosis infark akut miokard

dikonfirmasi dalam 96,1 persen pasien yang mengalami pengacakan; 3,6 persen memiliki

sindrom koroner akut, dan sisanya 0,3 persen diberikan diagnosa lain. Itu base-line

karakteristik klinis dari kedua kelompok pasien ditunjukkan dalamTabel 1.

Lihat tabel ini:

[di jendela ini]

[di jendela baru]

Tabel 1. Karakteristik Pasien di Base Line, Menurut Perawatan Group.

Primer Hasil Tindakan

Selama enam minggu pengobatan, kematian atau kongestif berat gagal jantung terjadi di 83

dari 784 pasien di plasebo kelompok (10,6 persen) dan di 55 dari 772 pasien di zofenopril

kelompok (7.1 persen)(Gambar 1);pengurangan risiko peristiwa kardiovaskular besar

seperti yang didefinisikan di atas adalah 34 persen (95 persen confidence interval, 8-54

persen; P = 0,018). Pengurangan risiko ini terutama disebabkan oleh penurunan dalam

insiden gagal jantung kongestif berat yang memerlukan open-label pengobatan dengan

inhibitor ACE, sedangkan relatif kontribusi kematian adalah statistik tidak signifikan(Tabel2). Ketika kami memeriksa kejadian kematian kumulatif dari semua penyebab terlepas dari

apakah ada sebelum kongestif gagal jantung, kami menemukan bahwa ada 65 kematian di

plasebo kelompok (8,3 persen) dibandingkan dengan 50 pada kelompok zofenopril (6,5

persen)(Tabel 3). Dengan demikian, pengurangan risiko kematian dari semua sebab selama

enam minggu masa pengobatan yang 22 persen (95 persen confidence interval, -12 sampai

48 persen; P = 0,17) dan hampir seluruhnya disebabkan oleh penurunan kardiovaskular

kematian dalam kelompok zofenopril (pengurangan risiko, 22 persen; Interval kepercayaan

95 persen, -8 sampai 53 persen; P = 0,08) (Tabel 3). Ada juga perbedaan yang mencolok

antara zofenopril kelompok dan kelompok plasebo dalam jumlah pasien yang meninggal

dalam waktu 24 jam setelah pengacakan (1 vs 8 kematian). Angka kematian akibat

penyebab noncardiac adalah serupa pada kedua perlakuan kelompok(Tabel 3).
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T1#T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T1#T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T1#T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F1#F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F1#F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F1#F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T3#T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T2#T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F1#F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T1#T1


13/16

View larger

version (2K):

[di jendela ini]

[di jendela

baru]

Gambar 1. Insiden Kematian atau parah Congestive Heart Failure selama Enam

Minggu dari Pengobatan dengan Zofenopril atau Placebo pada Penderita dengan

akut Myocardial Infarction.

Lihat tabel

ini:

[di jendelaini]

[di jendela

baru]

Tabel 2. Insiden parah Congestive Heart Failure atau Kematian sebagai Primary

Gabungan Titik Akhir Kajian.

Lihat

tabel ini:

[di jendela

ini]

[di jendela

baru]

Tabel 3. Kumulatif Insiden Maut dari Semua Penyebab Enam Minggu setelah dari

Pengobatan dengan Zofenopril atau Placebo, Terlepas dari Apakah Ada Sebelum Apakah

Congestive Heart Failure.

Hasil sekunder Ukuran

Selama enam minggu pengobatan angina terjadi pada 153 pasien (19,5 persen) pada

kelompok plasebo dan pada 128 pasien (16,6 persen) dalam kelompok zofenopril. Dengan

demikian, pengurangan risiko adalah 18 persen (95 persen confidence interval, -6 sampai 37;

P = 0,08). Setelah pengacakan, 23 pasien mempunyai setidaknya satu klinis melaporkan

non fatal infark miokard (12 pasien dalam kelompok plasebo dan 11 dalam kelompok

zofenopril). A total of 75 pasien (9,6 persen) pada kelompok plasebo memiliki tanda-tanda

klinis ringan sampai sedang gagal jantung kongestif setelah enam minggu, dibandingkan

dengan 52 pasien (6,7 persen) di zofenopril kelompok, dengan penurunan risiko di ambang

batas signifikansi statistik (pengurangan risiko, 29 persen; interval keyakinan 95 persen, -2

Ke 51; P = 0,054). Penggunaan obat lain selama enam minggu masa pengobatan adalah

sebanding pada kedua kelompok dengan kecuali penggunaan digoxin, yang diberikan kurang

sering untuk pasien yang memakai zofenopril daripada pasien yang memakai plasebo (5,8
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T3http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F1http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F1


14/16

persen vs 8,4 persen, P = 0,041), sebuah temuan yang konsisten dengan insiden lebih rendah

dari manifestasi klinis jantung kegagalan dalam kelompok ini (data tidak ditampilkan).

Satu tahun tingkat kematian bagi semua pasien sesuai dengan Tugas-tugas perawatan asli

ditunjukkan padaGambar 2. Pasien yang menerima selama enam minggu zofenopril secara

signifikan lebih mungkin bertahan hidup dibandingkan pasien yang diberikan plasebo.Selama tahun pengamatan 77 of 772 pasien dalam zofenopril kelompok (10,0 persen)

meninggal, dibandingkan dengan 111 dari 784 pasien di plasebo kelompok (14.1 persen),

dan perbedaan ini signifikan dipertanggungjawabkan pengurangan risiko kematian (29

persen; 95 persen keyakinan interval, 6-51; P = 0,011). Pengurangan risiko ini tidak dapat

dijelaskan oleh perbedaan dalam farmakologi seiring atau perawatan bedah, yang dipastikan

selama lebih dari 80 persen pasien(Tabel 4).

View larger

version (2K):

[di jendela ini]

[di jendela

baru]

Gambar 2. Kumulatif Mortalitas selama Satu Tahun Follow-up antara Pasien

dengan Myocardial Infarction akut untuk Enam Minggu Diobati dengan Zofenopril

atau Placebo.

Lihat tabel ini:[di jendela ini]

[di jendela baru]

Tabel 4. Treatments Diperintah ke Pasien selama Satu Tahun Pengamatan.

Analisis subkelompok

Tujuan utama dinilai dalam subkelompok yang ditetapkan di dasar karakteristik atau

perawatan yang dikenal untuk mempengaruhi kelangsungan hidup setelah infark miokard

(Tabel 5). Efek yang menguntungkan dari terapi zofenopril jelas pada pasien dengansebelumnya infark miokard dan pada mereka diperlakukan secara bersamaan dengan bloker

kanal kalsium dan nitrat selama perawatan di rumah sakit.

Lihat

tabel ini:

[di

endela

ini]

[di

endela

Tabel 5. Dampak Zofenopril di Akhir Primer Point (Kematian atau berat Congestive Heart

Failure) di subkelompok Ditetapkan di Dasar Perawatan Karakteristik atau farmakologi

Dikenal untuk Mempengaruhi Hasil pada Penderita dengan Myocardial Infarction.
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F2#F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F2#F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F2#F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T4#T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T4#T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T4#T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T5#T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T5#T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T5#T5http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content-nw/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80/F2http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23T4#T4http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23F2#F2


15/16

baru]

Tekanan darah Profil

Prevalensi keseluruhan hipotensi, konservatif didefinisikan sebagai tekanan darah sistolik di

bawah 100 mm Hg pada setiap saat selama penelitian, secara signifikan lebih tinggi pada

kelompok zofenopril (132 pasien, 17,1 persen) dibandingkan pada kelompok plasebo (70

pasien, 8,9 persen, P


16/16

manfaat yang dicapai melalui cardioprotective utama Efek27,28, 29dan juga melalui prompt

blokade efek dari neurohumoral aktivasi.30, 31A sebelumnya percobaan klinis yang

melibatkan intravena dan oral dari enalapril untuk pasien dengan infark miokard akut gagal

untuk menunjukkan efek menguntungkan apa pun perawatan dini dengan ACE inhibitor.16

Kami tidak menggunakan rute intravena administrasi.

Menariknya, efek yang menguntungkan dari pengobatan jangka pendek dengan zofenopril

dipertahankan dari waktu ke waktu, sebagaimana tercermin pada peningkatan ketahanan

hidup pada satu tahun. Meningkatkan data ini penting isu mengenai kemampuan kursus

singkat terapi untuk meningkatkan kelangsungan hidup jangka panjang pada pasien dengan

miokard akut miokard. Mekanisme manfaat yang terus-menerus bahkan setelah terapi telah

dihentikan masih harus diselesaikan. Lain telah menunjukkan bahwa perawatan dini dengan

ACE inhibitor dapat meningkatkan fungsi ventrikel kiri setelah infark miokard.32

Data saat ini ditambahkan ke semakin banyak bukti yang mendukung penggunaan ACE

inhibitor seperti di awal zofenopril saja anterior akut infark miokard. Kami menyarankan

administrasi awal ACE inhibitor pada pasien dengan infark miokard dapat dianggap sebagaistrategi yang masuk akal di sub-sub kelompok berisiko tinggi, terutama pada pasien dengan

anterior besar infark miokard.
http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R27#R27http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R27#R27http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R28#R28http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R28#R28http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R29#R29http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R29#R29http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R30#R30http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R30#R30http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R31#R31http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R31#R31http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R32#R32http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R32#R32http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R32#R32http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R32#R32http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R16#R16http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R31#R31http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R30#R30http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R29#R29http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R28#R28http://translate.google.com/translate?hl=id&sl=en&tl=id&prev=_t&u=http://content.nejm.org/cgi/content/full/332/2/80%23R27#R27

The Effect of the Angiotensin

Documents

Transcript of The Effect of the Angiotensin