***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: During the past 25 years , 24 r and omized trials of intravenous ( IV ) fibrinolytic treatment have been reported , involving a total of some 6000 patients in the acute phase of myocardial infa rct ion . Most tested IV streptokinase ( SK ) , but a few tested IV urokinase ( UK ) . In the past 2 or 3 years numerous small r and omized trials of intracoronary ( IC ) SK have been started , 9 of which , involving a total of about 1000 such patients , have been reported . Because all of these IV and IC trials were small ( the largest including only 747 patients ) , their separate results appear contradictory and unreliable . But , an overview of the data from these trials indicates that IV treatment produces a highly significant ( 22 % + /- 5 % , P less than 0.001 ) reduction in the odds of death , an even larger reduction in the odds of reinfa rct ion , and an absolute frequency of serious adverse effects to set against this that is much smaller than the absolute mortality reduction . The apparent size of the mortality reduction in the IV trials was similar whether anticoagulants were compulsory or optional , whether treatment was in a coronary care unit or an ordinary ward and , surprisingly , whether treatment began early ( less than 6 h from onset of symptoms ) or late ( generally 12 - 24 h ) . In addition , there was no evidence that UK was more effective than the less expensive SK , or that , despite their technical complexity , the new IC regimes were more effective than the old IV regimes . Even the IV schedules that have been studied in r and omized trials were , however , quite complex , and the IC schedules were far more so . Perhaps partly because of this , none of them is widely used . If so , then some much simpler , and hence more widely practicable , IV SK regimes should be developed and tested . For example , a simple one hour high-dose IV SK infusion , without anticoagulation , will successfully convert virtually all of the available plasminogen into plasmin . But , it may be several years before the net effects on mortality of any more widely practicable IV SK regimes can be agreed unless many of the hospitals that do not wish routinely to use IC regimes or the complex previous IV regimes will collaborate in multicentre r and omized trials that can , if necessary , continue rapid intake until some tens of thous and s of patients have been r and omized , and some thous and s of deaths have been observed among the control and treated patients . The same , of course , may be true for any other fibrinolytic regimes ( e.g. infusion of tissue plasminogen activator ) if their net effects on mortality are comparable to those of IV SK 41,299 patients entering 914 hospitals up to 24 h ( median 4 h ) after the onset of suspected acute myocardial infa rct ion were r and omised between streptokinase ( SK : 1.5 MU infused over about 1 h ) , tissue plasminogen activator ( tPA , duteplase : 0.60 MU/kg infused over about 4 h ) , or anisoylated plasminogen-streptokinase activator complex ( APSAC ) , anistreplase : 30 U over about 3 min ) . All patients were to receive aspirin ( 162 mg/day enteric-coated ) , with the first tablet chewed for rapid and full antiplatelet effect . Half of all patients were r and omly allocated subcutaneous calcium heparin ( 12,500 IU starting at 4 h and given twice daily for 7 days or until prior discharge ) in addition to aspirin , and the other half were to receive aspirin alone . ASPIRIN PLUS HEPARIN VERSUS ASPIRIN ALONE -- The addition of heparin to aspirin was associated with an excess of transfused or other major non-cerebral bleeds ( 1.0 % aspirin plus heparin vs 0.8 % aspirin alone ; 2p < 0.01 ) and of definite or probable cerebral haemorrhage ( 0.56 % vs 0.40 % ; 2p < 0.05 ) , but with no significnat differences in total stroke ( 1.28 % vs 1.18 % ) . Reinfa rct ions were slightly less common among those allocated aspirin plus heparin ( 3.16 % vs 3.47 % ; 2p = 0.09 ) . There was no signficant difference in the pre-specified endpoint of 35-day mortality ( 2132 [ 10.3 % ] aspirin plus heparin vs 2189 [ 10.6 % ] aspirin alone ) . During the scheduled heparin treatment period there were slightly fewer deaths in the aspirin plus heparin group ( days 0 - 7 in hospital : 1534 [ 7.4 % ] vs 1633 [ 7.9 % ] ; 2 p = 0.06 ) , with a slight convergence by day 35 ( 598 further deaths [ 3.1 % of survivors ] vs 556 [ 2.9 % ] ) . The pattern was similar to that observed in the GISSI-2 trial , so that in both trials combined there was a significant reduction in mortality during the scheduled treatment period ( 2071 [ 6.8 % ] vs 2239 [ 7.3 % ] ; 2p < 0.01 ) . This indicates avoidance of 5 deaths ( SD 2 ) per 1000 patients allocated this high-dose subcutaneous heparin regimen in addition to aspirin , but some of any early benefit may be lost after heparin ceases , with no significant mortality advantage in days 0 - 35 ( both trials : 3100 [ 10.0 % ] vs 3172 [ 10.2 % ] ) or during follow-up to 6 months . SK VERSUS APSAC -- APSAC was associated with significantly more reports of allergy causing persistent symptoms and of non-cerebral bleeds , but not of transfused bleeds or of reinfa rct ions . There was a slight excess of strokes with APSAC ( 1.04 % SK vs 1.26 % APSAC ; 2p = 0.08 ) , much of it appearing soon after treatment started ( strokes during days 0 - 1 : 0.50 % SK vs 0.73 % APSAC ; 2p < 0.02 ) and being attributed to cerebral haemorrhage ( 0.24 % SK vs 0.55 % APSAC ; 2p < 0.0001 ) . No significant difference was observed in reinfa rct ion ( 3.47 % SK vs 3.55 % APSAC ) . There was no significant mortality difference during days 0 - 35 , either among all r and omised patients ( 1455 [ 10.6 % ] SK vs 1448 [ 10.5 % ] APSAC ) or among the pre-specified subset presenting within 0 - 6 h of pain onset and with ST elevation on the electrocardiogram in whom fibrinolytic treatment may have most to offer ( 861 [ 10.0 % ] SK vs 855 [ 9.9 % ] APSAC ) . No significant difference in 6-month survival was apparent overall or in the subset . ( ABSTRACT TRUNCATED AT 400 WORDS Clinical investigators have long pursued the elusive dream of finding a cheap , safe treatment that reduces mortality and morbidity in a common condition . Many investigators had hoped that magnesium given intravenously to patients with acute myocardial infa rct ion might be such a treatment . Were they justified ? Small trials reporting the use of magnesium in acute myocardial infa rct ion have been reported intermittently for 20 years . The rationale for these studies came partly from observations of differences in heart attack rates associated with geographical variations in magnesium in the water supply and partly from laboratory studies showing that magnesium had cardioprotective effects during ischaemia and that myocardial magnesium concentrations were relatively low during acute ischaemia.1 Research on animals has shown that magnesium is a peripheral and coronary vasodilator , has antiarrhythmic effects , decreases reperfusion injury , and has antiplatelet effects in some species.1 The clinical importance of these findings is , however , still uncertain . Experimental studies often do not have the same rigorous design , conduct , and analysis that are now expected from clinical research . Few experimental studies are r and omised or blinded . Furthermore , publication bias is likely , with positive results being more likely to be reported than negative ones — especially when the subject is a relatively new hypothesis . An informal review of the results of the early clinical trials in acute myocardial infa rct ion indicated a trend towards a lower mortality with intravenous magnesium , with this difference being statistically significant in only one trial.2 That trial also found a reduction in arrhythmias . These impressions were subsequently confirmed by a formal meta analysis .3 The data came , however , from only 1300 patients with a In a study with 2 x 2 factorial design , 20,891 patients with suspected acute myocardial infa rct ion of less than 6 h duration ( 12,490 from the GISSI-2 trial and 8401 recruited elsewhere ) were r and omly allocated to alteplase ( recombinant tissue plasminogen activator , tPA ) or streptokinase ( SK ) and to subcutaneous heparin , beginning 12 h after the start of thrombolytic therapy or no heparin . The protocol recommended that , in the absence of specific contraindications , all patients should receive aspirin and intravenous beta-blockade as soon as possible . No significant differences in hospital mortality were found between tPA and SK ( 8.9 % versus 8.5 % ) or between heparin and no heparin ( 8.5 % versus 8.9 % ) . The incidence of major cardiac complications was also very similar in the different groups . For non-cardiac complications significant differences between the treatment groups were observed : more strokes were reported with tPA than with SK ( 1.3 % versus 1 % ) while more major bleeds occurred with SK than with tPA ( 0.6 % versus 0.9 % ) . Subcutaneous heparin was likewise associated with an excess of major bleeds ( 1.0 % with heparin versus 0.5 % without heparin ) but did not affect the incidence of stroke or reinfa rct ion To compare the effects of two thrombolytic agents , streptokinase and recombinant tissue-type plasminogen activator ( rTPA ) with early heparinization , on left ventricular function , coronary patency and reinfa rct ion rates , bleeding complications , and short- and long-term mortality , we studied 122 patients with acute myocardial infa rct ion prospect ively . All of them fulfilled the st and ard criteria for thrombolytic therapy . One group ( n = 63 ) received 1,500,000 units of streptokinase over 1 hour , and one group ( n = 59 ) received 100 mg of rTPA over 3 hours . Baseline data showed no significant differences between the streptokinase and rTPA groups . Results of predischarge studies 10 to 14 days after infa rct ion revealed that there was no difference in left ventricular ejection fraction between the two groups ( 48.3 % in the streptokinase group and 49.9 % in the rTPA group ; p = 0.67 ) . The patency rate of the infa rct -related artery tended to be higher in the rTPA group compared with the streptokinase group ( 77 % vs 57 % , p = 0.19 ) . In-hospital spontaneous bleeding occurred after streptokinase in seven patients ( 11.1 % ) and after rTPA in eight ( 13.6 % ; p = 0.89 ) . One patient had intracranial bleeding after rTPA and died 13 hours later . The early mortality rate within 30 days of acute myocardial infa rct ion was 5 of 63 ( 7.9 % ) for the streptokinase group and 2 of 59 ( 3.4 % ) for the rTPA group ( p = 0.49 ) . During the 19.3-month follow-up period , reinfa rct ion occurred in seven patients ( 11 % ) in the streptokinase group and in three ( 5 % ) in the rTPA group ( p = 0.3 ) . The mortality rates were 10 of 63 ( 16 % ) and 3 of 59 ( 5 % ) , respectively ( p = 0.1 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Intravenous administration of 80 mg of recombinant tissue plasminogen activator ( rt-PA , 40 , 20 , and 20 mg in successive hours ) and streptokinase ( SK , 1.5 million units over 1 hr ) was compared in a double-blind , r and omized trial in 290 patients with evolving acute myocardial infa rct ion . These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted . Ninety minutes after the start of thrombolytic therapy , occluded infa rct -related arteries had opened in 62 % of 113 patients in the rt-PA and 31 % of 119 patients in the SK group ( p less than .001 ) . Twice as many occluded infa rct -related arteries opened after rt-PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy . Regard 
    Output:
    
For available comparisons ( all alteplase vs. streptokinase , reteplase vs. streptokinase or alteplase , tenecteplase vs. alteplase ) , meta- analysis showed no significant differences in mortality at 30 - 35 days .
The GUSTO-I study showed an apparent benefit of accelerated alteplase over streptokinase , but its inclusion or exclusion made little difference .
DISCUSSION All thrombolytic drugs appear to be of similar efficacy in reducing mortality , and the apparent benefits of accelerated alteplase in GUSTO-I are consistent with this .