- Email: [email protected]
Shoulo thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study
mxtemyocarmbusresults in reduction in 1 and enh~~eme~t of survival (f,g). Any delay h~rn~~yt~~t~~~~y has a critaealimpact on the ~~~~~~ationTherefore, the prehosthe:mqjsr front i4 the battle for revascu~~~~~dy et al. (9) to state that ‘“the of ~~tmve~?ous or in uscllk~rtbron~bo~yt~~ must be studied.” tlon (b-4),
ments of Chmhbgy,
T&Aviv*
and Shebat
Medical
; revised manuscript received huwy
1~. 6 Weizmsn
, Depamentof Cardiology, Street. Tel Aviv 64239. Israel,
TeLAviv
study was initiated by r 1986, PP~ol~abo~~t~ve the Sheba and Tel- viv Medical Centers in Israel to assess the feasibility, safety and possible advantage ofearly administration of r~~ornb~~antt~~~~~~~~y~~ ~lasmiu~gemactivator @t-PA)in the mobile intensive care unit, which in Israel is staRed by a physician or intern as well as by paramedics.
These were 1) age 473 years, 2) severe
my~cardial ischemic chest pain for 330 than 4 h, and 3) ST segment elevation of 0.1 mV or more in at least two contiguous ele~t~oc~d~ographic (KG) leads. Exclusioncriteria. Ttiese were 1) diastoiic blood pressure >I20 mm Hg, 2) left bundle brunch block on the qualifying entry KG, 3) history of congestive heart failure or cardiac
(for instarxe, oral a~tic~~a~~~~a~ttherapy, recent trauma, past bl~edi~~~ history, or ce~ebr~vascu~ar acc~de~~lwiulin the iast 6 months).
after signing an informed consent a~reemenl were allocated on an alternating monthly rotation basis to receive prehospital thrombolytic treatment by the mobile intensive care unit team or thrombolytic therapy in the coronary care unit (87 patients). An additional successive 29 patients who enrolled th er received prehospital apy via the le intensive care unit. T maintained telemetric commumicat~o~ with the medical centter. All patients were continuous mias and vital signs were obtain ’ tra il arrival (Fig. 1). tat A total dose of 120 mg of rccomb~~~ant re tissue-type plasminogen activator (rt-PA) (Grl1035, supplied by Boehrittger Ingelheim, West Germany) was administered over a 6 h period, consisting of a 10 mg bolus followed by
pe~ormed in the anterior and 45” left anterior oblique projections. Left ventricular ejection fictions were detcrmined and all radionuclide exarn~~at~~~s were assessed by
ilalized in the corona
ood samples were also
934
JACC Vol. 15, No. 5 April 1990932-6
ROTH ET AL. &HOSPITAL THROMBOLYSIS
plasminogenactivity, fibrinogenlevel and partial thromboplastin time at baseline. S&II Y&a ata are expressedas meanvalues f 1 standarddeviationunlessotherwisestated.Student’sI test was used to compare groups with approximatelynormal distribution, while nonparametricgroup comparisonswere evaluated using the Mann-WhitneyIJ test. The chi square test or Wilcoxontest was used for unpairedsamples.
r to receive treatment spital coronarycaIy3unit
Table 1.
Baseline Characteristics in Patients Assigne Recombinant Tissue-Type Plasminogen Activator @t-PA)in the Mobile Intensive Care Unit (MICU) (group A) and in the Coronary Care Unit(CCtJ)(group B)
Ageiyrb Gender (% men) Body mass index (kg/m21 Hypertension (%I Smekon (%,) Diabetes mellitus (%I Angina pectoris (!JQ Previous infarct (%h) Systolic blood pressure (mm Ngl Heart rate (~e;~ts/fl~~~) Killip scale (%I
58 2 9 82 26 & 3 20 50 I4
NS
I UP2
NS NS
30r4 Location of infarct (%I Anterior Inferior Fibrinol)cn (rn~~~ ml)
NS NS MS MS
Plasminogea activity(954 No.of diseased vessels (%I*
care unit. Two patients in group A were excluded from
NS NS NS N 0.05 NS NS NS NS
I
NS NS
2 or more ~nfar~t~relate~ coronary artery (95) Left anterior descending Left cirsumfkzx
NS NS NS
*Sixty-five patients in group A and 43 Patients in group
~t~~~tone~ in two patients. only three patientsrequiringbl Tabk 2. Time to Thrombolytic Therapy, Enzyme Release, Left
~ent~c~~arEjection Fraction on Admission and Patency of the tnf~~~t-~~~at~d Artery in the Two Patient Groups
Timeto therapy (min)
c6 Of asymptomaticacceleratedids wereobservedin two patientsin group B. Threepatientsin groupA and wo in degrees of bradyarrhythmiaswithout compromisethat requiredintervention.
CK peak (ICI) CK AUC (IIJ) LVEF (%) IRA patent (o/n!
Group A (MICU, n = 72)
Group B (CCU. n = 44)
P Value
94 ” 35 1346 + 1541 7109 + 6882 47 5 M (43*) 82 (65%)
137 r: 45 It 939 + 4856 48 + 15 (41*) 77 143*1
NS NS NS
*No. of patients examined. AUC = area under the curve; CK = cmatine kinase; IRA = infarct-related coronary artery; LVEF = left ventricular ejection fraction. Other abbrevia:ions as in Table 1.
intravenous reco
The rec~g~itiQn of the i~~o~tanc~ of early a~~licaFi~~ of thrombolytic therapy in myocardial ~~fa~~tio~ led i~ist~Fi0~ of Iytic to the investigation oT mber of ~e~Q~ed ~atic~ts Table 4. In-Hospital
Clinical Course in the Two Patient Groups Group A
ChJkOlrmfZ
Bleeding (%) PTCA (%I CABG (%) Reinfafction (%) Mortality (%‘c) LtnEih of stav Idw;s)
slotted ~~r~~a~y artery. hospital patients can be tr
(NICU.
n =
14 42 (65”) 7 13.9 5.5 11
Group 13
72)
KCU,n = 44) 9 56 (43? s 13.6 6.R I4
P
Value NS NS NS NS NS NS
*No. of patients catheterized. CABG = coronary artery bypass graft; RCA = percutaneous transluminal coronary angioplasty. Other abbreviations as in Table I.
(82% versus 77%), there was an increased left v~~t~i~~~~r ejection fraction (49 -‘- 17% vbrsus 45 &t 1995) a
trends in favor of
Fhrombolytic trial ( I&) ventricdar function, patients wko had an anterior infarction
936
JACC Vol. 15. No. 5 April I :932-B,
RQTH ET AL. PREHOSPlTAL THROMBOLYSIS
benefited from early thrombolytic treatment more than those who had an inferior infarction. We compared the global left ventricular ejection fraction of patients with anterior infarction treated in the mobile unit (n = 33) with that of patients treated in the coronary care unit (n = 19) but did not observe any difference, Hoiiever, the small number of patients precludes any conclusions being drawn, the same being true for the corresponding patients with inferior infarction Gable 5). The GISSl study (5) demonstrated that in-hospital mort&y was reduced when thcr.zpy was given within 3 h of more so when treatment wits initiated tion. The ISAM trial (19) also indicated point for improved survival, but other t that the therapeutic “window” may My if thrambolysis is combined with angioplasty. Studies compar and performed in Jerusalem, myocardial salvage, few incorrect diagnoses and a ncc of repcrfusion arrhythmias, hemorrhage .;r other complications (I 1.21.22). ?%a rerlson3 we were uronhle to demon.stmte ~i~n~~~~~lt br?nefit of earlier treatment mcry he one or both of the following: I) the 44 min delay may have keen too short to
display significant difference: 2) although streptokinasc may lose its effectiveness with time, recombinnnt tissue-type plasminogen activator retains a h h cfkacy even with u longer delay (10,231. for early t~r~~r~bolysis thus remains very st nstntes that myocarnosed and that early administration of recombinant tiss pc pl~srnin~~~e~activator by a mobile intensive cBre unit team is feasible and We were unable to demonstrate a signifile outcome in the prehospital early treatment we believe that the evidence the be time element in thrombol the n the latt ventricular ejection fraction and tive heart failure in the prehospital grwp ~uppm the pt’ehospital thrombolysis in the routine management nts with acute myocardial infarction, We are indebted lo Eli hadas. MD, lbe paramedics of the Israel Mqcn David Adorn and the nurses and medical technicians of the Departments of Cardim the %&a and Tel-Aviv Medical Centers for referral of patients and assistance in their care.
administration 68:131-8.
during evolving myocardial
infarction.
Circulation
1983;
ge HT. tXect of 3. Sheehan FH, Mathey DG. Schafer J. Krebber HJ. interventions in salvaging left ventricular function in acute myocardial infarction: a study of intracoronary streptokinase. Am J Cardiol 198352: 431-8. 4. Spann JF. Sherry S, Carabello BA, et al. Coronary thrombolysis by intravenous streptokinase in acute myocardial infarction: acute and follow-up studies. Am J Cardiol ~9~4:53:65~-6~. 5. GISSI. Long-term effects of intravenous thrombolysis in acute myocarI study. Lancet ~9~~~2:$71-4. dial infarction: final report of the &it?. SK. Western 6. Kennedy JW. Ritchie JL. Davis randomitcd trial of intracorona e~t~)~~nas~ in ilCUk infarction. N Engl J Med l9$3:3~t477~~2.
Was~~~~t~~~ rn~~~ilr~i~i~
7. !&they DG, Schofcr J. Sheehan FH. 61 al, ~~~~r~~v~d survival years after early coronnry th~orn~~~ysis. Am J Cerdiol 098R;(il 8. 1,61$$2 (Second ~ot~r~~lti~~na~ Study of Iuliltrct Survival) ~~~l~lll~~r~~t~v~ Group. Haadomised trin! of intr~iven~~os st~~tok~~l~s~, oral nsl~i~~~. both. or neither umong If.lX7 cases of suspected rtrutr nryocurrlitrl in~~~~cti~~~: ISIS-2. Lnncet lYHH;I:349-60. 9. Kcnncdy JW. Atkins JM, Goldstch~ S. ct sl. Recent changes io 1~1~1~~~1~~~ for c~cr~c~cy can ment of acute myeccardial i~f~~r~tio~~* physicians, J Am Coil Cardiol 198&l I: IO. TIM1 Study Group: The th~rnl~~lysis trial: Phase I findings. N F.nyl J hled
in my~rdi~~~
i~~l~t~~~o I’FI
I I. Martens U. Lange-~ra~ln I’. Larger ysc des akuten ~y~~koi~iufarks: vet pitalphnsc. Deutch Mcd Wschr 1987 12. Gotsman MS. Weirs AT. ~~~scnheck S. et al. Early thr~)fll~~ys~s preserves LV function (abstr). Eur H J (suppl) ~9~~;~:215. 13. Nicholas J. Hi&son JDS, Uoyl Early intervention in myoca infarction wi?b sl~~~l~~~~~~~scnt O& in accidfnt and e dcpnrtmcnt (nbstr). Eur &art J ~s~~~~~)t9~~;~2~2. Schafer J. Vocilz P, et al. ~‘rcbos~it~~ tb~nl~~ysis in acute infarction: time gain and co~i~~licatio~s (abstr). Eur Heart J (sq~pl) 198)8X;‘):H. IS. McAlccr U. Varma MPS. Use 0ftLom lytic ~hc~l~y io rural co~~lil~l~ity outside hospital (abstr). Eur Heart J ~~~~~11 I 13s.
hus@d~com~ina~t uppl) l9~~;~2~4~ I?. Topol EJ. Fun@ AY. Kline E, et al. Safety of k&copter tmas~rt an out-of-hospital intravenous ~br~no~yt~c thyroid in ~atioats with evolving myocardial infarction. Cath Ca asc Diag 1986;12: ISI-5. 18. Kennedy JW. Ritchie JL, Davi , Studius ML. ~ay~~~~~ C. Fritz JK. The Western Washiqtor rando d trial of ~ntra~~~n~ry stre~takinas~ in acute myocardial infarction: a Q-month follow-up report. N Engl J Med 1985:31231073-8. 19. The I.S.A.M. Study Group. A prospective trial of intravenous streptokie in acute myocardial infarction. N Engl J Med 1986;314:1465-71. 20.
ry A3. Michelsan EL. W&r FJ. Dreifus LS. Thrombolytic therapy of acute myocnrdial infarction: emerging challenges of implementation. J Am Co11 Cardiol l9~7:l~l3~?-~.
21. Weiss AT. Fine DG, Appelbaum D. et al. ~rebos~ital coronary throwbulpsis; A new slratcgy in acute l~~y~ard~a~ iofarctioe. Chest 1987392: 124-8. p KP. Blanke H, Karsch KR. Effects of nonsurgical coronary the left ventricle in human subjects compared with nt. Am J Cardiol 198249:1-8.
s F. Matthews MW, et al. Sustained improvement in le%t ventricular
timction and mortality
by intracoronary
streptokinase
22. Bippus PH. Haux R, Schrodcr R. Prehospital intravenous streptokinasc in evolving myocardial infarction: a randomised study about feasibility. safety. and time-gain (abstr). Eur Heart J (suppl) 1987;8:103. 23. van de Wcrf F , Llidbrxk PA. Bergman SR. Clot selective coronary thmmbolysis with tissue-type plasminogen activator in patients with evolving myxardial infarction. N Engl J Med 1984;310:609-13.
ments of Chmhbgy,
T&Aviv*
and Shebat
Medical
; revised manuscript received huwy
1~. 6 Weizmsn
, Depamentof Cardiology, Street. Tel Aviv 64239. Israel,
TeLAviv
study was initiated by r 1986, PP~ol~abo~~t~ve the Sheba and Tel- viv Medical Centers in Israel to assess the feasibility, safety and possible advantage ofearly administration of r~~ornb~~antt~~~~~~~~y~~ ~lasmiu~gemactivator @t-PA)in the mobile intensive care unit, which in Israel is staRed by a physician or intern as well as by paramedics.
These were 1) age 473 years, 2) severe
my~cardial ischemic chest pain for 330 than 4 h, and 3) ST segment elevation of 0.1 mV or more in at least two contiguous ele~t~oc~d~ographic (KG) leads. Exclusioncriteria. Ttiese were 1) diastoiic blood pressure >I20 mm Hg, 2) left bundle brunch block on the qualifying entry KG, 3) history of congestive heart failure or cardiac
(for instarxe, oral a~tic~~a~~~~a~ttherapy, recent trauma, past bl~edi~~~ history, or ce~ebr~vascu~ar acc~de~~lwiulin the iast 6 months).
after signing an informed consent a~reemenl were allocated on an alternating monthly rotation basis to receive prehospital thrombolytic treatment by the mobile intensive care unit team or thrombolytic therapy in the coronary care unit (87 patients). An additional successive 29 patients who enrolled th er received prehospital apy via the le intensive care unit. T maintained telemetric commumicat~o~ with the medical centter. All patients were continuous mias and vital signs were obtain ’ tra il arrival (Fig. 1). tat A total dose of 120 mg of rccomb~~~ant re tissue-type plasminogen activator (rt-PA) (Grl1035, supplied by Boehrittger Ingelheim, West Germany) was administered over a 6 h period, consisting of a 10 mg bolus followed by
pe~ormed in the anterior and 45” left anterior oblique projections. Left ventricular ejection fictions were detcrmined and all radionuclide exarn~~at~~~s were assessed by
ilalized in the corona
ood samples were also
934
JACC Vol. 15, No. 5 April 1990932-6
ROTH ET AL. &HOSPITAL THROMBOLYSIS
plasminogenactivity, fibrinogenlevel and partial thromboplastin time at baseline. S&II Y&a ata are expressedas meanvalues f 1 standarddeviationunlessotherwisestated.Student’sI test was used to compare groups with approximatelynormal distribution, while nonparametricgroup comparisonswere evaluated using the Mann-WhitneyIJ test. The chi square test or Wilcoxontest was used for unpairedsamples.
r to receive treatment spital coronarycaIy3unit
Table 1.
Baseline Characteristics in Patients Assigne Recombinant Tissue-Type Plasminogen Activator @t-PA)in the Mobile Intensive Care Unit (MICU) (group A) and in the Coronary Care Unit(CCtJ)(group B)
Ageiyrb Gender (% men) Body mass index (kg/m21 Hypertension (%I Smekon (%,) Diabetes mellitus (%I Angina pectoris (!JQ Previous infarct (%h) Systolic blood pressure (mm Ngl Heart rate (~e;~ts/fl~~~) Killip scale (%I
58 2 9 82 26 & 3 20 50 I4
NS
I UP2
NS NS
30r4 Location of infarct (%I Anterior Inferior Fibrinol)cn (rn~~~ ml)
NS NS MS MS
Plasminogea activity(954 No.of diseased vessels (%I*
care unit. Two patients in group A were excluded from
NS NS NS N 0.05 NS NS NS NS
I
NS NS
2 or more ~nfar~t~relate~ coronary artery (95) Left anterior descending Left cirsumfkzx
NS NS NS
*Sixty-five patients in group A and 43 Patients in group
~t~~~tone~ in two patients. only three patientsrequiringbl Tabk 2. Time to Thrombolytic Therapy, Enzyme Release, Left
~ent~c~~arEjection Fraction on Admission and Patency of the tnf~~~t-~~~at~d Artery in the Two Patient Groups
Timeto therapy (min)
c6 Of asymptomaticacceleratedids wereobservedin two patientsin group B. Threepatientsin groupA and wo in degrees of bradyarrhythmiaswithout compromisethat requiredintervention.
CK peak (ICI) CK AUC (IIJ) LVEF (%) IRA patent (o/n!
Group A (MICU, n = 72)
Group B (CCU. n = 44)
P Value
94 ” 35 1346 + 1541 7109 + 6882 47 5 M (43*) 82 (65%)
137 r: 45 It 939 + 4856 48 + 15 (41*) 77 143*1
NS NS NS
*No. of patients examined. AUC = area under the curve; CK = cmatine kinase; IRA = infarct-related coronary artery; LVEF = left ventricular ejection fraction. Other abbrevia:ions as in Table 1.
intravenous reco
The rec~g~itiQn of the i~~o~tanc~ of early a~~licaFi~~ of thrombolytic therapy in myocardial ~~fa~~tio~ led i~ist~Fi0~ of Iytic to the investigation oT mber of ~e~Q~ed ~atic~ts Table 4. In-Hospital
Clinical Course in the Two Patient Groups Group A
ChJkOlrmfZ
Bleeding (%) PTCA (%I CABG (%) Reinfafction (%) Mortality (%‘c) LtnEih of stav Idw;s)
slotted ~~r~~a~y artery. hospital patients can be tr
(NICU.
n =
14 42 (65”) 7 13.9 5.5 11
Group 13
72)
KCU,n = 44) 9 56 (43? s 13.6 6.R I4
P
Value NS NS NS NS NS NS
*No. of patients catheterized. CABG = coronary artery bypass graft; RCA = percutaneous transluminal coronary angioplasty. Other abbreviations as in Table I.
(82% versus 77%), there was an increased left v~~t~i~~~~r ejection fraction (49 -‘- 17% vbrsus 45 &t 1995) a
trends in favor of
Fhrombolytic trial ( I&) ventricdar function, patients wko had an anterior infarction
936
JACC Vol. 15. No. 5 April I :932-B,
RQTH ET AL. PREHOSPlTAL THROMBOLYSIS
benefited from early thrombolytic treatment more than those who had an inferior infarction. We compared the global left ventricular ejection fraction of patients with anterior infarction treated in the mobile unit (n = 33) with that of patients treated in the coronary care unit (n = 19) but did not observe any difference, Hoiiever, the small number of patients precludes any conclusions being drawn, the same being true for the corresponding patients with inferior infarction Gable 5). The GISSl study (5) demonstrated that in-hospital mort&y was reduced when thcr.zpy was given within 3 h of more so when treatment wits initiated tion. The ISAM trial (19) also indicated point for improved survival, but other t that the therapeutic “window” may My if thrambolysis is combined with angioplasty. Studies compar and performed in Jerusalem, myocardial salvage, few incorrect diagnoses and a ncc of repcrfusion arrhythmias, hemorrhage .;r other complications (I 1.21.22). ?%a rerlson3 we were uronhle to demon.stmte ~i~n~~~~~lt br?nefit of earlier treatment mcry he one or both of the following: I) the 44 min delay may have keen too short to
display significant difference: 2) although streptokinasc may lose its effectiveness with time, recombinnnt tissue-type plasminogen activator retains a h h cfkacy even with u longer delay (10,231. for early t~r~~r~bolysis thus remains very st nstntes that myocarnosed and that early administration of recombinant tiss pc pl~srnin~~~e~activator by a mobile intensive cBre unit team is feasible and We were unable to demonstrate a signifile outcome in the prehospital early treatment we believe that the evidence the be time element in thrombol the n the latt ventricular ejection fraction and tive heart failure in the prehospital grwp ~uppm the pt’ehospital thrombolysis in the routine management nts with acute myocardial infarction, We are indebted lo Eli hadas. MD, lbe paramedics of the Israel Mqcn David Adorn and the nurses and medical technicians of the Departments of Cardim the %&a and Tel-Aviv Medical Centers for referral of patients and assistance in their care.
administration 68:131-8.
during evolving myocardial
infarction.
Circulation
1983;
ge HT. tXect of 3. Sheehan FH, Mathey DG. Schafer J. Krebber HJ. interventions in salvaging left ventricular function in acute myocardial infarction: a study of intracoronary streptokinase. Am J Cardiol 198352: 431-8. 4. Spann JF. Sherry S, Carabello BA, et al. Coronary thrombolysis by intravenous streptokinase in acute myocardial infarction: acute and follow-up studies. Am J Cardiol ~9~4:53:65~-6~. 5. GISSI. Long-term effects of intravenous thrombolysis in acute myocarI study. Lancet ~9~~~2:$71-4. dial infarction: final report of the &it?. SK. Western 6. Kennedy JW. Ritchie JL. Davis randomitcd trial of intracorona e~t~)~~nas~ in ilCUk infarction. N Engl J Med l9$3:3~t477~~2.
Was~~~~t~~~ rn~~~ilr~i~i~
7. !&they DG, Schofcr J. Sheehan FH. 61 al, ~~~~r~~v~d survival years after early coronnry th~orn~~~ysis. Am J Cerdiol 098R;(il 8. 1,61$$2 (Second ~ot~r~~lti~~na~ Study of Iuliltrct Survival) ~~~l~lll~~r~~t~v~ Group. Haadomised trin! of intr~iven~~os st~~tok~~l~s~, oral nsl~i~~~. both. or neither umong If.lX7 cases of suspected rtrutr nryocurrlitrl in~~~~cti~~~: ISIS-2. Lnncet lYHH;I:349-60. 9. Kcnncdy JW. Atkins JM, Goldstch~ S. ct sl. Recent changes io 1~1~1~~~1~~~ for c~cr~c~cy can ment of acute myeccardial i~f~~r~tio~~* physicians, J Am Coil Cardiol 198&l I: IO. TIM1 Study Group: The th~rnl~~lysis trial: Phase I findings. N F.nyl J hled
in my~rdi~~~
i~~l~t~~~o I’FI
I I. Martens U. Lange-~ra~ln I’. Larger ysc des akuten ~y~~koi~iufarks: vet pitalphnsc. Deutch Mcd Wschr 1987 12. Gotsman MS. Weirs AT. ~~~scnheck S. et al. Early thr~)fll~~ys~s preserves LV function (abstr). Eur H J (suppl) ~9~~;~:215. 13. Nicholas J. Hi&son JDS, Uoyl Early intervention in myoca infarction wi?b sl~~~l~~~~~~~scnt O& in accidfnt and e dcpnrtmcnt (nbstr). Eur &art J ~s~~~~~)t9~~;~2~2. Schafer J. Vocilz P, et al. ~‘rcbos~it~~ tb~nl~~ysis in acute infarction: time gain and co~i~~licatio~s (abstr). Eur Heart J (sq~pl) 198)8X;‘):H. IS. McAlccr U. Varma MPS. Use 0ftLom lytic ~hc~l~y io rural co~~lil~l~ity outside hospital (abstr). Eur Heart J ~~~~~11 I 13s.
hus@d~com~ina~t uppl) l9~~;~2~4~ I?. Topol EJ. Fun@ AY. Kline E, et al. Safety of k&copter tmas~rt an out-of-hospital intravenous ~br~no~yt~c thyroid in ~atioats with evolving myocardial infarction. Cath Ca asc Diag 1986;12: ISI-5. 18. Kennedy JW. Ritchie JL, Davi , Studius ML. ~ay~~~~~ C. Fritz JK. The Western Washiqtor rando d trial of ~ntra~~~n~ry stre~takinas~ in acute myocardial infarction: a Q-month follow-up report. N Engl J Med 1985:31231073-8. 19. The I.S.A.M. Study Group. A prospective trial of intravenous streptokie in acute myocardial infarction. N Engl J Med 1986;314:1465-71. 20.
ry A3. Michelsan EL. W&r FJ. Dreifus LS. Thrombolytic therapy of acute myocnrdial infarction: emerging challenges of implementation. J Am Co11 Cardiol l9~7:l~l3~?-~.
21. Weiss AT. Fine DG, Appelbaum D. et al. ~rebos~ital coronary throwbulpsis; A new slratcgy in acute l~~y~ard~a~ iofarctioe. Chest 1987392: 124-8. p KP. Blanke H, Karsch KR. Effects of nonsurgical coronary the left ventricle in human subjects compared with nt. Am J Cardiol 198249:1-8.
s F. Matthews MW, et al. Sustained improvement in le%t ventricular
timction and mortality
by intracoronary
streptokinase
22. Bippus PH. Haux R, Schrodcr R. Prehospital intravenous streptokinasc in evolving myocardial infarction: a randomised study about feasibility. safety. and time-gain (abstr). Eur Heart J (suppl) 1987;8:103. 23. van de Wcrf F , Llidbrxk PA. Bergman SR. Clot selective coronary thmmbolysis with tissue-type plasminogen activator in patients with evolving myxardial infarction. N Engl J Med 1984;310:609-13.