Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-µmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

Expression of inducible nitric oxide synthase in human coronary atherosclerotic plaque.

OBJECTIVE: Macrophages in atherosclerotic plaque may express the inducible isoform of NO synthase (iNOS), which produces large amounts of NO. On one hand, the production of NO can be protective by its vasodilatory, antiaggregant and antiproliferative effects. On the other hand, the formation of peroxynitrite from NO may favour vasospasm and thrombogenesis. In this study, we investigated whether iNOS is present in human coronary atherosclerotic plaque, and we correlated these data with the clinical instability of the patients. METHODS: Fragments were retrieved by coronary atherectomy from 24 patients with unstable angina and 12 patients with stable angina. The presence of macrophages, and the production of TNF alpha, iNOS and nitrotyrosine were detected by immunocytochemistry. RESULTS: Macrophage clusters were found in 67% of stable patients and 87% of patients with unstable angina (NS). TNF alpha was expressed in about 50% of cases in both groups. iNOS was not expressed in fragments from stable patients but was found in macrophages from 58% of unstable patients (P < 0.001). The expression of iNOS was associated with the presence of nitrotyrosine residues, a marker of peroxynitrite formation. Expression of iNOS was correlated both with complaints of angina at rest (P < 0.05) and with the presence of thrombus at morphological examination (P < 0.001). CONCLUSION: The expression of iNOS may be induced in human coronary atherosclerotic plaque and is associated with different factors of instability.

Pathology of unstable plaque: correlation with the clinical severity of acute coronary syndromes.

OBJECTIVES: The aim of this study was to relate the various clinical presentations of acute coronary syndromes to the underlying plaque morphology as assessed from histopathologic analysis of plaque fragments obtained by directional coronary atherectomy (DCA). BACKGROUND: Autopsy studies have shown that unstable angina and infarction are related to plaque instability and involve events such as fissure or rupture of the fibrous cap, thrombosis and inflammation. The clinical severity and prognosis of acute coronary syndromes can be estimated by the Braunwald classification of unstable angina. Whether plaque morphology can be related to the Braunwald classification has not been evaluated. METHODS: Plaque fragments were obtained by DCA in 75 patients: 38 with unstable angina, 19 with stable angina and 18 with no symptoms after infarction. The presence of fibrous tissue, thrombus, high cellularity, inflammatory cells, atheroma, neovessels and "stellar-shaped" smooth muscle cells was evaluated in 7-micron thick sections by appropriate staining. The patients were classified according to clinical presentation without knowledge of the results of pathologic examination, and a plaque instability score was assigned. The risk of further cardiac events was classified as low, medium or high. RESULTS: Increasing severity of the score of unstable angina was associated with increasing prevalence of thrombus, high cellularity, atheroma and neovessels. Plaque from patients with unstable angina considered to be at low risk of further events appeared very similar to that of patients with stable angina, whereas the specific morphologic characteristics of plaque instability were more frequently observed as the clinical score and the risk of further events increased. After thrombolyzed infarction, plaque morphology depends on the delay between the acute event and DCA. Within 1 week after infarction, plaque still showed the morphologic characteristics of instability, whereas late DCA provided samples with morphologic features similar to those observed in patients with stable angina. CONCLUSIONS: The morphologic features of plaque fragments vary at different stages of acute coronary disease. The specific features of plaque instability correlate with the clinical scoring system of the Braunwald classification.

Clinical benefit of angiotensin converting enzyme inhibition after acute myocardial infarction: myocardial reperfusion revisited.

BACKGROUND: Beneficial effect has been reported from angiotensin converting enzyme (ACE) inhibition after acute myocardial infarction (AMI) in several experimental and large clinical studies showing improvements in haemodynamics, left ventricular remodelling and mortality. However, this benefit has not been prospectively evaluated after AMI effectively reperfused using current coronary recanalization techniques. CLINICAL ISSUE: The clinical relevance of reperfusion therapies including thrombolysis or percutaneous transluminal coronary angioplasty relates to their ability to limit infarct size and left ventricular dysfunction and reduce infarct-related morbidity and mortality. The clinical issue is to determine whether ACE inhibitors should be routinely proposed as an adjunct therapy in patients with a patent infarct-related vessel after AMI. RESULTS OF RECENT STUDIES: Three placebo-controlled randomized trials addressed this issue in evaluating the left ventricular remodelling process (i.e. left ventricular volumes and ejection fraction changes) during a 3 to 4-month follow-up period. The Captopril and Thrombolysis Study and the Captopril plus Tissue plasminogen activator after Myocardial Infarction trials failed to show any significant preventive effect of early captopril therapy on remodelling in patients admitted for anterior AMI and treated with conventional use of streptokinase and alteplase, respectively. In the Salvage from Perindopril in Reperfused Infarction Trial, no beneficial effect on global left ventricular remodelling was observed from perindopril therapy in a population with effective myocardial reperfusion confirmed at angiography and moderately depressed left ventricular function. However, in this study ACE inhibition seemed to favourably alter remodeling in a subgroup of AMI patients with anterior location and large infarct size despite successful reperfusion. CONCLUSION: Recommendation for ACE inhibition as a routine adjunct therapy to reperfusion techniques is not supported by current data on short-term left ventricular function changes.

Coronary angiographic findings do not predict clinical outcome in patients with unstable angina.

OBJECTIVES: The presence of thrombus formation and type of coronary artery lesion were determined in patients with unstable angina and correlated with the angiographic findings and clinical outcome. BACKGROUND: Some previous studies have suggested that thrombus formation and lesions are predictive of the angiographic and clinical findings. This was evaluated in a retrospective analysis of 159 patients participating in the placebo-controlled Unstable Angina Study Using Eminase (UNASEM) trial on the effect of thrombolysis in unstable angina. METHODS: Patients without a previous myocardial infarction who presented with a typical history of unstable angina in the presence of abnormal findings on the electrocardiogram indicative of ischemia were included in the study. After baseline angiography, study medication (anistreplase or placebo) was given to 126 to 159 patients. Thirty-three patients did not receive medication because of significant main stem disease or normal coronary arteries or for other reasons. Angiography was repeated after 12 to 28 h. RESULTS: Quantitative angiography showed a significant decrease in diameter stenosis in the anistreplase-treated group compared with the placebo-treated group (decrease 11% vs. 3%, p = 0.008). No differences in clinical outcome were found when thrombolytic treatment was compared with placebo (p = 0.98). Neither the presence nor absence of thrombus formation (p = 0.98) nor the type of lesion (p = 0.96) was related to the changes in diameter stenosis or to clinical outcome (p = 0.90 and p = 0.77, respectively). The power of these analyses to detect a 20% difference varied between 56% and 74%. CONCLUSIONS: In this selected group of patients with unstable angina, type of coronary artery lesion and the presence or absence of thrombus formation does not predict clinical outcome.

Clinical and angiographic outcome following implantation of the new Less Shortening Wallstent in aortocoronary vein grafts: introduction of a second generation stent in the clinical arena.

One of the factors felt to have contributed to the high rate of stent occlusion in the European registry of the coronary Wallstent in the 1980s was the frequent deployment of more than one stent to cover the target lesion. This resulted from a high degree of shortening of the Wallstent upon expansion. To overcome this limitation the design of the Wallstent was modified to reduce the degree of shortening. We report the results of a study of the first patients to undergo implantation of the new Less Shortening Wallstent. Thirty-five Wallstents were electively deployed in aortocoronary vein grafts in 29 patients. Stent deployment was successful in 35 of 36 attempts in 30 lesions. In five of the 30 lesions, a second stent was required to cover the proximal portion of the lesion. Angiographic success (< 50% residual diameter stenosis as determined by off-line quantitative coronary angiography) was achieved in all 29 patients. During the in-hospital phase, no major adverse cardiac event occurred (reintervention, re-CABG, myocardial infarction, or death) and five patients had hemorrhagic complications. Following hospital discharge, one patient had a subacute stent occlusion associated with symptoms and elevated cardiac enzymes at 11 days, another patient had symptoms and elevated cardiac enzymes (CK 300 U/I) at 22 days with a patent stent, five patients required balloon angioplasty within the 6 month follow-up period (four for restenosis and one for stent occlusion), one patient underwent re-CABG for a native artery stenosis distal to the anastomosis of the patent stented vein graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Basic components and patterns of acute ischemia recovery assessed from continuous ST monitoring in acute myocardial infarction treated by thrombolytic therapy.

Continuous ST monitoring of the lead showing the highest ST elevation on the admission 12-lead electrocardiogram was performed in patients with acute myocardial infarction of 6 hours or less enrolled in the OSIRIS and GUSTO trials. ST elevation measured at j + 50 ms was averaged from all normal beats every 20 seconds. ST trends were visually analyzed by two observers blinded from the thrombolytic treatment, its onset, and coronary angiograms performed 21 hours (median) after thrombolysis. Three basic and consecutive components were considered for analysis: the initial amplitude of ST elevation (A1), the maximal amplitude recovery (REC), and the minimal ST amplitude (A2). Prespecified patterns (PAT) were considered: PAT 1 integrated permanent A1 elevation followed by REC, PAT 2 intermittent A1 elevation, and REC. Prespecified pattern 3 was considered in absence of REC. Twenty-four-hour trends were recorded in 347 patients and judged adequate in 306 (88%) followed by angiography in 268 (77%). This group was not clinically different from the 79 patients without ST/angiography. Prespecified pattern 1 was identified in 81%, PAT 2 in 8%, and PAT 3 in 11% of the patients. The positive predictive value of PAT 1 + 2 for coronary patency was 94%, the negative predictive value 72%, sensitivity 96%, and specificity 60%. A salient feature was the occurrence of ST overshoot defined by a > or = 1 mm increase above A1 within the first minutes of REC. Overshoot occurred in 35% of PAT 1 and predicted subsequent patency in all but two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism of directional coronary atherectomy.

An attempt was made to assess the mechanism of directional coronary atherectomy using different methods of analysis. Quantitative coronary angiography was used as the gold standard to assess the immediate results of atherectomy, and a comparative quantitative analysis of atherectomy and balloon angioplasty was made. To determine whether the post-atherectomy cross-sectional area is close to a circle, we compared the area measurements obtained by edge detection with those obtained by videodensitometry. Finally, the extent of a 'Dotter' effect was established by quantitative angiography following crossing the stenosis with the atherectomy device. For the purpose of this study, the results of the first 113 successful atherectomy procedures were reviewed. In matched lesions, directional atherectomy induced a greater increase in minimal luminal diameter than balloon angioplasty (1.6 mm vs 0.8 mm; P < 0.0001). However, this luminal improvement is due to a substantial 'Dotter' effect induced by the bulky atherectomy device. Following atherectomy, only a slight difference in cross-sectional area measurements between edge detection and videodensitometry (mean difference: 0.28 mm2) was found. Histologic examination of an atherectomized coronary artery showed a near-circular postatherectomy area geometry. In conclusion, directional atherectomy is a very effective device with a substantially better initial result than balloon angioplasty. However, insertion of this bulky device itself causes an important 'Dotter' effect.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.

OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

One hundred and thirteen attempts at directional coronary atherectomy: the early and combined experience of two European centres using quantitative angiography to assess their results.

Directional coronary atherectomy has been introduced as an alternative to conventional balloon angioplasty when treating coronary artery stenoses with complex lesion morphology. To determine the immediate efficacy of coronary atherectomy in patients with such lesions, the first 113 attempts at directional atherectomy in two centres using quantitative angiography were reviewed in 105 patients. The lesions were classified as complex stenosis since 95% had a symmetry index less than 1.0, a length of 6.83 +/- 2.55 mm on average and an area of plaque of 9.77 +/- 6.69 mm2. Procedural success defined as a residual stenosis less than or equal to 50% after tissue retrieval was obtained in 90 (85.7%) of 105 patients. The primary angioplastic success rate, combining atherectomy and balloon angioplasty in case of failed attempt of atherectomy was 95.2%. Coronary atherectomy was unsuccessful in five patients; three were referred for emergency coronary artery bypass grafting. Major complications (death, emergency surgery and transmural infarction) were encountered in 5.7% of the patients. Assessed by quantitative coronary analysis, a residual minimal luminal diameter of 2.42 +/- 0.52 mm and a diameter stenosis of 26 +/- 12% were obtained immediately after directional coronary atherectomy. We conclude that directional coronary atherectomy is particularly suitable for the treatment of stenosis with complex lesion morphology and is associated with acceptable complication rates. Randomized trials comparing atherectomy with balloon angioplasty are warranted to clarify the role of atherectomy in the treatment of lesions in the proximal part of the three major epicardial coronary arteries.

Percutaneous transluminal coronary angioplasty of the left coronary artery in patients with chronic occlusion of the right coronary artery: clinical and functional results.

The safety and therapeutic benefits of percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery, the left circumflex coronary artery or both were assessed in 61 patients with chronic (greater than 3 months) occlusion of the right coronary artery. Recanalization of the right coronary artery was not performed before dilatation of left coronary artery lesions. All lesions could be dilated without an acute ischemic event in the catheterization laboratory. However, three patients underwent coronary artery bypass surgery within the first 8 days after coronary angioplasty. There were no in-hospital deaths. Of the remaining 58 patients, 51 (88%) had repeat angiography at a mean of 5.2 +/- 2.5 months. Patients were divided into two groups according to the presence (n = 17) or absence (n = 34) of restenosis defined as greater than or equal to 50% diameter stenosis at the dilated site. Baseline characteristics were comparable. The mean value for angina functional class at follow-up was significantly better in the group without than in the group with restenosis (0.4 +/- 0.6 vs 2.1 +/- 1.1, respectively; p less than 0.001). Sixty-five percent of the patients without restenosis were asymptomatic at follow-up. Seventy-five percent of the predicted maximal physical capacity was reached by 76% of the patients without restenosis compared with 33% in the group with restenosis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty of coronary bifurcation stenoses: immediate and long-term results of the protecting branch technique.

Percutaneous transluminal angioplasty (PTCA) of coronary stenoses involving major bifurcations carries a small but significant risk of side branch occlusion which can be avoided by simultaneously using multiple dilatation systems. Among 1,275 PTCA procedures performed between 1984 and 1988 in 1,035 consecutive patients, 42 double wire procedures were applied (4%) to protect and/or dilate major coronary side branches. A total of 80 coronary stenoses were attempted of which 76 were located on a bifurcation and 4 on other segments. In the first 11 patients (group A), 2 guiding catheters were used and PTCA of each vessel was successfully performed by means of separate double lumen over-the-wire balloon catheters. In the next 31 patients (group B), 2 guidewires were advanced through a single guiding catheter and PTCA was attempted using "Monorail" balloon catheters sequentially advanced over the wires. In group B, a successful PTCA was obtained in 29 patients (93%) but twisting of the wires hampered balloon progression in 5 cases, such that dilatation could only be performed by stepping back to a single wire technique. The procedure time in group B was significantly shorter than in group A: 144 +/- 30 versus 230 +/- 52 minutes (p = .01). Repeat angiography was performed in 35 out of 40 patients (87%) after a mean of 180 +/- 46 days following successful PTCA. Angiographic restenosis was present in 37% (24/65) of bifurcation segments which, in our experience, is not significantly different from the angiographic restenosis rate in less complex lesions (248/740; 34%; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac tamponade early after thrombolysis for acute myocardial infarction: a rare but not reported hemorrhagic complication.

Among 392 consecutive patients admitted for acute myocardial infarction and treated with thrombolytic drugs, 4 patients (1%) developed an early hemorrhagic pericardial effusion (without ventricular wall rupture) evolving within 24 h to cardiogenic shock consequent to cardiac tamponade. They all suffered from a large anterior myocardial infarction treated within 4 h after onset of symptoms with intravenous anisoylated plasminogen streptokinase activator complex (one case), recombinant tissue-type plasminogen activator (rt-PA) (two cases) or streptokinase (one case), anticoagulation with heparin (all cases) and aspirin (three cases). As soon as pericardial effusion was established by echocardiography, emergency percutaneous pericardiocentesis was performed at the bedside 20 +/- 6 h after thrombolytic therapy was started. This corrected immediately the clinical and hemodynamic status of each patient and a catheter was left in the pericardial space for 34 +/- 18 h. Thus, in the presence of unexplained clinical and hemodynamic deterioration occurring during the first 24 h after thrombolytic treatment of a large myocardial infarction, cardiac tamponade should be suspected. Immediate percutaneous pericardiocentesis followed by continuous drainage is a simple and definitive treatment for this complication.

Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables.

A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of segmental hypokinesis by coronary angioplasty in patients with unstable angina, persistent T wave inversion, and left anterior descending coronary artery stenosis. Additional evidence for myocardial stunning in humans.

To evaluate the significance of persistent negative T waves during severe ischemia, we prospectively studied 62 patients admitted for unstable angina without evidence of recent or ongoing myocardial infarction. A critical stenosis on the left anterior descending coronary artery (LAD), considered as the culprit lesion, was successfully treated by percutaneous transluminal coronary angioplasty (PTCA). The patients were divided into two groups according to the admission electrocardiogram: T NEG group (n = 32) had persistent negative T waves, and the T POS group (n = 30) had normal positive T waves on precordial leads. The two groups had similar baseline clinical, hemodynamic, and angiographic characteristics. All patients underwent a complete clinical and angiographic evaluation (coronary arteriography and left ventriculography) before undergoing PTCA and 8 +/- 3 months later. Left ventricular anterior wall motion was evaluated by the percent shortening of three areas (S1, S2, and S3) considered as LAD-related segments on left ventriculograms. Before PTCA, there was no significant difference in global ejection fraction between the two groups despite a significant depression in anterior mean percent area shortening in the T NEG compared with the T POS group (S1, 44 versus 54, p less than 0.01; S2, 39 versus 48, p less than 0.01; S3, 44 versus 50, NS). At repeated angiography, the anterior mean percent area shortening improved significantly in the T NEG group (S1, from 44 to 61, p less than 0.001; S2, from 39 to 58, p less than 0.001; S3, from 44 to 61, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction.

The systemic activator activity of 4 streptokinase (SK) regimens (250,000 IU intracoronary, group A; 500,000 IU, group B; 1.5 X 10(6) IU, group C; and 30 U anisoylated plasminogen streptokinase activator complex (APSAC) intravenously, group D) was tested with the fibrin plate technique. One hour after initiation of treatment, the activator activity was highest after APSAC (3.6 +/- 0.9 U), slightly but not significantly less after SK 1.5 X 10(6) IU (3.0 +/- 0.7), and significantly less after SK 500,000 IU (1.6 +/- 0.5) and 250,000 IU (0.6 +/- 0.5), p less than 0.001. After SK, activator activity half-lives were 184 minutes (group B) and 169 minutes (group C), and after APSAC 188 minutes (group D). These were all in agreement with greater than 12 hour duration of changes in other markers of systemic fibrinolysis (euglobulin lysis time) and substrates depletion (fibrinogen, plasminogen, alpha 2 antiplasmin). In extended pilot clinical groups given identical thrombolytic regimens during full anticoagulation with heparin, angiographic coronary patency was found in 83% (35 of 42) after intracoronary SK (group 1), in 73 and 75%, respectively, after 500,000 IU (31 of 43) and 1.5 X 10(6) IU (30 of 40) (group 2 and 3, difference not significant) and 80% (8 of 10) after the 30-U bolus of APSAC (group 4). The overall hemorrhagic risk was 24%, equally distributed among the 4 regimens and mostly (91%) related to catheters. The incidence of bleeding unrelated to vessel puncture was 4%; no deaths occurred. It is concluded that APSAC is the most fibrinolytic regimen but its potential thrombolytic superiority over SK remains to be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of coagulation and fibrinolysis after intravenous anisoylated plasminogen streptokinase activator complex or heparin in patients with acute myocardial infarction. A Belgian multicentre study.

A multicentre randomised trial including 87 patients admitted for acute myocardial infarction compared the effects of a single intravenous bolus of an anisoylated plasminogen streptokinase activator complex (APSAC) 30 units with those of heparin treatment on haemostasis during the first 4 days after treatment. In the APSAC group, a rapid and significant reduction in fibrinogen, plasminogen and alpha 2-antiplasmin was observed, associated with an increase of fibrin(ogen) degradation products, reflecting a strong systemic lytic activity. None of these parameters were significantly modified by heparin, but the anticoagulant effect was apparent as assessed by the activated partial thromboplastin time. The systemic fibrinolysis induced after different regimens of streptokinase infusion demonstrated that an intravenous bolus of APSAC 30U was as potent as streptokinase 500,000 or 1,500,000IU administered intravenously over 45 minutes and definitely more fibrinolytic than intracoronary infusion of streptokinase 250,000IU. Despite the demonstrated fibrin specificity of the drug at a low dose, a high dose of APSAC (30U intravenously) induced an important systemic lytic state for at least 12 hours.