Thrombolytics are equivalent and heparin confers no benefit in acute MI - findings of 2 major studies

Using a combined endpoint ... Streptokinase and alteplase do not differ clinic­

ally as treatment for acute myocardial infar~tion (MI), finds the multicentre Ita~ian GISSI-2. tna!.

Since alteplase and streptokmase have dlffer~nt pharmacological profiles but are both .effectl."e treatments for MI, a multicentre randomlsed tnal was conducted to compare their efficacies in a large population. The trial also assessed the. value of heparin treatment. 12 381 evaluable patients were randomised to receive IV alteplase 100mg over 3 hours or IV streptokinase 1.5MU over 0.5-1 hour, with or without SC heparin 12 500U bid. Throm­bolysis began within 6 hours of sympto.m. ~n~et and heparin was started 12 ~ours aft~r 1~ltIatlOn of thrombolysis and was contmued untIl discharge. All patients without contraindications also received oral aspirin 300-325 mg/day (87%) and IV atenolol 5-lOmg (45.3%) upon diagnosis.

Death clincal congestive heart failure or exten­sive left ~entricular damage occurred in a mean of 22.8% of patients in each of the 4 treatment groups, with no significant differences between any of the groups and an overall mortality o~ 8.8%. . .

Allergic reactions and hypotensl.on were ~1~lfi­cantly more frequent in streptokmase recIpients than alteplase recipients, but did not produce se­rious adverse consequences. Overall stroke rate and incidence of minor bleeds were lower in strepto­kinase recipients whereas major bleeds were less frequent in alteplase recipients. Hepa~n increased the risk of bleeding but decreased the nsk of throm­boembolic events. The incidences of adverse ef­fects (all strokes 1 %; major bleeds 0.8%; minor bleeds 7.4%; and thromboembolic events 0.6%) were sufficiently low to confirm a favourable risk: benefit ratio for thrombolysis.

With respect to the study endpoints, 'tile eff«ts of SK [streptolcilUlU} tUUI tPA [altepltue} do IIOt seem ~o differ ill any s.bstutial c1illicallUp«t ••• ' and hepann + aspirin does not confer any ~ter bene~t than aspirin alone. It is possible that I.f IV hepann an~ alteplase therapies were admimstered concomI­tantly rather than as per the study protocol, the results would favour alteplase and heparin more than in the present study, but data which support

ISSN 0156-2703/90/0728-0001/0$01.00/0 () Adis Intel7lllt;olllll Ltll

this hypothesis have so far been conflicting and de­rived from small studies. Gruppo Italiano per 10 Studio della Sopravvivenza nell'Infano Miocar­dico. GISSI-~: a factorial randomised trial of aiteplase versus streptoki­nase and heparin versus no heparin among 12490 patients with acute myocardial infarction. Lancet 336: 65-71. 14 Jul 1990

... and using mortality as the only endpoint Using mortality as the sole indi~ator of effica~y,

streptokinase and alteplase ~re eqUlvale~t. therapies for acute myocardial infarctIOn and addItIonal hep­arin therapy has no effect.

U sing the 2 x 2 factorial design and dosage schedules of the GISSI-2 study [see above], patients with acute myocardial infarction were randomly al­located to treatment with alteplase (n = 5202), al­teplase + heparin (5170), streptokinase (5205) and streptokinase + heparin (5191).8401 of the 20 7~8 patients were recruited outside of t~e GISSI-2 t~al and the remainder were analysed m both studIes. This larger study was conducted to compare the treatments in terms of mortality only.

Inhospital fatality rates were 8.9% in alteplase recipients and 8.5% in streptokinase recipieI?-ts. Be­tween-group mortality rates .were not different within any subgroup defined m te~s ?f gen~er, age, timing of thrombolysis or prevIous mf~rctIon. Evidence for interaction between hepann and thrombolytic therapies was weak, and no statistical differences between heparin and no heparin were found in fatality rates, stroke rates or incidence of reinfarction. As in GISSI-2, major bleeds were more common in streptokinase and heparin recipients than alteplase and no heparin recipients, res~c­tively, but the differences did not affect mortalIty.

'From the equal clinical outcome of the present study one could conclude that, although tPA [altepllUe} giFes more rapid lysis of coronary artery thrombi, the clinical benefits of the two thrombolytic agents depelld also on fac­tors such IU decretUed blood Fiscosity and /ate coronary patellCY in which the efficacy is the same for both agen~s or eFen higher for SK [streptokinlUej.' Althou~ add~­tive benefits from heparin were not seen m thIS study, other studies have indicated advan~ge~ with combination therapy; ISIS-3 should prOVIde mfor­mation on the benefits of earlier administration of heparin. The International Study Group. In-hospital monality and clinical course of 20 891 patients with suspected acute myocardial infarction random­ised between altepIase and streptokinase with or without heparin. Lancet 336: 71-75. 14 JuI 1990 """

13 INPHARMA® 28 Jill 1990 _