Accelerated streptokinase in ST-elevation myocardial infarction--a Romanian (ASK-ROMANIA) multicenter registry.

BACKGROUND: The classical streptokinase regimen (1.5 M.U. over 60 min) may be too slow in patients with ST-elevation myocardial infarction (STEMI). OBJECTIVE: To compare the efficacy and safety of four streptokinase regimens in STEMI patients. METHODS: 1880 consecutive patients admitted within 6 h of STEMI onset were allocated one of the following four streptokinase regimens: 1.5 M.U. over 60 min (n=517); 1.5 M.U./30 min (n=355); 1.5 M.U./20 min (n=507); 0.75 M.U./10 min, repeated or not after 50 min if no electrocardiographic criteria of reperfusion (n=501). RESULTS: Rates of coronary reperfusion (non-invasively detected) for SK1.5/30 (72.39%), SK1.5/20 (75.34%) and SK0.75/10 (72.85%) were similar and higher than for SK1.5/60 (64.03%, p=0.019, p<0.0001, and p=0.006, respectively). In-hospital mortality was significantly lower for SK1.5/20 (7.10%) and SK0.75/10 (7.38%) and at the limit of significance for SK1.5/30 (7.60%) compared with SK1.5/60 (11.60%, p<0.0001, 0.006, and 0.053, respectively). Intracerebral haemorrhage and other major bleeding had similar incidence in the four groups. CONCLUSIONS: Compared to the classical 1.5 M.U. over 60 min streptokinase regimen, significantly higher rates of coronary reperfusion and lower in-hospital mortality can be obtained by infusing the same dose over only 20 min, or either one or two half doses over only 10 min, without risk increase.

Accelerated streptokinase and enoxaparin in ST-segment elevation acute myocardial infarction (the ASENOX study).

BACKGROUND: The streptokinase (SK) regimen (1.5 MU/60 min) has remained unchanged in the ST-segment elevation acute myocardial infarction (STEMI) for the last 20 years. AIM: To compare the efficacy of an accelerated SK (ASK) regimen combined with enoxaparin (Enox) or heparin (UFH) with the standard SK and UFH combination in STEMI. METHODS: 633 consecutive patients, aged 21-74 years, admitted within 6 hours after the onset of STEMI, were divided in three groups: (1) ASKEnox (n=165): Enox 40 mg. i.v. followed by SK 1.5 MU over 20 min, either as a full dose or a double infusion of 0.75 MU over 10 min. separated by 50 min. After SK infusion, Enox was administered 1 mg/kg s.c. every 12 hours for 5-7 days; (2) ASKUFH (n=264): the same ASK regimen plus UFH 1,000 IU/h for 48-72 hours, (3) SSKUFH (n=204): SK 1.5 MU/60 min. plus UFH 1,000 IU/h for 48-72 hours. All patients received aspirin. Three coronary reperfusion (CR) criteria were used: 1. rapid cessation of chest pain; 2. rapid reduction of ST-segment elevation by more than 50% of the initial value; 3. rapid increase in plasma CK and CK-MB with a peak in the first 12 hours. RESULTS: The rates of CR in the ASKEnox (77.6%) and the ASKUFH (73.5%) groups were similar but both were significantly higher than that observed in the SSKUFH group (62.2%) (p=0.002 and 0.013, respectively). The 30-day mortality rates were similar in the ASKEnox (6.06%) and the ASKUFH (6.81%) groups but both were significantly lower than in the SSKUFH group (12.74%) (p=0.048 and 0.044, respectively). SK-induced hypotension was more frequent in the ASKEnox (39.4%) and ASKUFH (38.3%) groups compared with the SSKUFH group (20.6%) (p<0.0001), but it was transient and well tolerated. Haemorrhagic stroke occurred in two patients from the SSKUFH and one patient from the ASKUFH groups. CONCLUSIONS: ASKEnox and ASKUFH regimens are safe and result in a significantly higher rate of CR and a lower in-hospital mortality compared with the traditional SSKUFH regimen.

Streptokinase-induced hypotension has no detrimental effect on patients with thrombolytic treatment for acute myocardial infarction. A substudy of the Romanian Study for Accelerated Streptokinase in Acute Myocardial Infarction (ASK-ROMANIA).

UNLABELLED: The Streptokinase (SK) regimen (1.5 MU/60 minutes) has remained unchanged for the past 20 years in patients with ST-segment elevation acute myocardial infarction (STEMI) due to fear of hypotension (a specific effect of this thrombolytic agent) and of hemorrhagic complications. OBJECTIVE: To evaluate the influence of the Streptokinase-induced hypotension (SK-hTA) on the rate of coronary reperfusion (CR), incidence of cardiogenic shock (CS), 30-day mortality and incidence of stroke in patients (pts.) with STEMI. The SK-hTA was defined as decrease of the systolic blood pressure with at least 20% within the first 20 min. after the start of the SK infusion. METHODS: A group of 837 pts. (age 20-90) with thrombolytic treatment, with three "accelerated" SK regimens within the first 6 hours after the onset of STEMI and enrolled in the Romanian open, prospective, non-randomised study for accelerated SK in STEMI (ASK-ROMANIA) have been included. The SK regimens consisted in infusing of the standard dose of 1.5 M.U. either in 30 min. (regimen SK1.5/30, 173 pts).) or in 20 min. (regimen SK1.5/20, 377 pts.) or of the half dose (0.75 M.U.) in 10 min. followed by a new infusion of 0.75 M.U. after 50 min. only if no bed-side signs of CR have been recorded (regimen SK 0.75/10, 287 pts.). The speed of the SK infusion was maintained in all pts. experiencing SK-hTA. All pts. received aspirin and heparin or enoxaparin if not contraindicated. Three noninvasive CR criteria have been used: 1. Rapid cessation of the chest pain. 2. Rapid decrease of the ST segment elevation by more than 50% of the initial value. 3. Rapid increase of the CK and CK-MB with a peak within the first 12 hrs. RESULTS: SK-hTA appeared in 372 pts. (44.55%) at 9+/-5 min after the start of the SK infusion. In this subgroup the rate of CR was 74.46%, non-significantly higher than the one of 68.81% registered in pts. without SK-hTA (p=0.071). SK-hTA disappeared in all patients after 16+/-6 minutes without a specific therapy. Fourteen pts. with SK-hTA (3.76%) and 16 pts. without SK-hTA (3.44%) developed CS after thrombolysis ( non-significant difference). The global in-hospital mortality was 10.21% in pts. with SK-hTA and 9.89% in pts. without this side effect (non-significant difference). The incidences of hemorrhagic and ischemic strokes were 0.26% (1 patient) respectively 0.52% (2 pts.) in the SK-hTA subgroup and 0.43% (2 pts.) respectively 0.64% (3 pts.) in the subgroup without SK-hTA. CONCLUSIONS: 1. Despite a very high incidence (44.55%) the SK-hTA has not a detrimental effect in pts. treated with accelerated SK regimens for STEMI. 2. Streptokinase can be rapidly administered without an increased risk.

Double bolus of 0.75 MU streptokinase plus enoxaparin versus front-loaded alteplase plus unfractionated heparin in ST-segment elevation myocardial infarction.

OBJECTIVE: To compare the efficacy and safety of an accelerated streptokinase regimen (double bolus of 0.75 MU in 10 min) in combination with enoxaparin (SK0.75Enox regimen) with the one of the front loaded alteplase (t-PA 100 mg/90 min) plus heparin (the t-PAHep regimen) in patients (pts.) with ST-segment elevation acute myocardial infarction (STAMI). METHODS: One hundred seventy three pts. (age 18-74) treated within the first 6 hrs. after the onset of STAMI with the above two mentioned thrombolytic regimens were included. 1. The group SK0.75Enox (102 pts.) received an i.v. bolus of 40 mg Enox followed by 0.75 MU SK in 10 min. A second bolus of 0.75 MU SK would be administrated only if no bed-side signs of coronary reperfusion (CR) were detected within the next 50 min. After thrombolysis Enox was administered 1 mg/kg bodyweight every 12 hrs. for 5-7 days. 2. The group t-PAHep (71 pts.) received 15 mg oft-PA in bolus followed by 50 mg in 30 min and 35 mg within the next 60 min; t-PA was followed by heparin 1000 u/hour for the next 48-72 hours. All the patients received aspirin. Three noninvasive CR criteria were used: 1. Rapid cesation of the chest pain. 2. Rapid decrease of the ST segment elevation by more than 50% from the initial value. 3. Rapid increase of the CK and CK-MB with a peak within the first 12 hrs. RESULTS: Two patients (2.85%) from the t-PAHep group had non-fatal stroke (one haemorrhagic, one ischemic). No other major haemoragical events were registered in both groups. During the thrombolytic infusion hypotension appeared more frequently in the SK0.75Enox group (31.4%) than in the t-PAHep one (8.5%) (p>0.0001) but without any consequence regarding the patients' outcome. The ratio of CR was 78.4% in the SK0.75Enox group and 70.4% in the t-PAHep one (p = 0.308). In-hospital reocclusion appeared in 4 pts. from the t-PAHep group (5.7%) but in none in the SK0.75Enox one. Six pts. (5.9%) from the SK0.75Enox group and 5 pts. from the t-PA one (7.04%) died within the first 30 days after the onset of STAMI (p = 0.993). CONCLUSIONS: The combination SK0.75Enox is at least as safe and efficacious as the t-PAHep one.

Efficacy and safety of a new streptokinase regimen with enoxaparin in acute myocardial infarction.

OBJECTIVE: To compare a new streptokinase regimen combined with either enoxaparin or unfractionated heparin (UFH) and the traditional streptokinase regimen combined with UFH in patients with acute myocardial infarction (AMI). METHODS: 412 patients (<75 years), hospitalized within 6 hours of the onset of chest pain, were allocated thrombolytic therapy by the treating physician: streptokinase 0.75 MU/10 minutes, repeated if no coronary reperfusion after one dose, plus enoxaparin 40 mg intravenously followed by 1 mg/kg bodyweight subcutaneously at 12-hour intervals for 5-7 days (n = 102); the same streptokinase regimen plus UFH 1000 IU/60 minutes intravenously for 48-72 hours ( n = 106); or streptokinase 1.5 MU/60 minutes plus the same UFH regimen (n = 204). All patients received 250-325 mg aspirin/day. Coronary reperfusion rates, 30-day mortality and hemorrhagic complications were recorded. RESULTS: Coronary reperfusion rates with 0.75 streptokinase + enoxaparin (78.4%) and 0.75 streptokinase + UFH (74.5%) were significantly higher than those with 1.5 streptokinase + UFH (62.2%), but there was no significant difference between the groups receiving the new regimen. Overall 30-day mortality (6.3%) was significantly lower than with 1.5 streptokinase + UFH (12.7%) ( p = 0.037). The incidence of major and minor hemorrhagic events was similar in all groups. CONCLUSIONS: The accelerated streptokinase regimen was well tolerated and resulted in a significantly higher coronary reperfusion rate and significantly lower mortality compared with the traditional regimen. The 0.75 streptokinase + enoxaparin combination was at least as efficacious as the 0.75 streptokinase + UFH combination and is preferred because of its ease of administration and predictable anticoagulant effect.

QT & RR variability spots the earliest autonomic deregulation in diabetes. Fading of vagal sino-atrial drive but not of sympathetic ventricular responsiveness to life challenges.

27 consecutive insulin-dependent diabetic patients (pts), under 50 years, with blood glucose controlled within normal limits and no significant or multiple cardiovascular/neurological complications in the lights of clinical tests, went through a protocol as follows: laiddown at relaxed rest for 10 min, then stood-up quietly for 7 min, and finally experienced a stress-interview for 10 min while supine. A thoracic ECG lead was digitized at I ms (Codas, Dataq Instr.), RR and QT intervals were software-detected, resampled at 500 ms, and Fourier-transformed over 3 min epochs to get auto-or cross-spectra. RR-by-QT mean square coherence detached the RR-independent fraction of QT low fequency (LF) spectral power, called idioventricular QT-LF. We detected autonomic impairment of three types (discriminant score = 92.31%), presumably differentiated upon the locus of lesion, using RR's basal variance and mean RR shortening when standing as follows: (I) RR shortening > 200 ms in 10 pts; (II) normal RR shortening but no RR variance in 4 pts; (III) stiff RR around 600 ms and no RR variance in 2 pts. The above pts have been excluded from further analysis. The remaining 11 pts with no such impairments (5M and 6F, 36.4 y +/- 4.4 SD, history of 6.0 y +/- 5.2) have been compared with 11 normal subjects in an age and gender-paired control group in two steps. Step 1: Preliminary MANOVA/ANOVA showed significant effects on the ensemble of spectral variables of every single factor (status: normal or patient group; intervention; gender) with no significant factor interactions. Significant effects of intervention or status on main RR spectral variables and on a few QT spectral variables were also documented. Step 2: Non-parametric tests showed that diabetics had (mildly to moderately) shorter mean RR, while their RR-LF was always significantly lower than those found in normals--a difference propagated to QT-LF but not to idioventricular QT-LF. In the intra-group there were similar responses to interventions except stress with respect to mean RR. Consistent reduction in RR-LF under moderate or no change in mean RR suggests vagal down- regulation that, judging by idioventricular QT-LF showing, goes perhaps before a similar process with sympathetic control of ventricles. This phase delay may introduce an early arrhythmic risk worth dealing with in secondary prevention.