4. GaspozJ-M, Lee TH, Cook EF, Weisberg MC, Goldman L. Outcome of patients who were admitted to a new shortstay unit to “rule-out” myocardial infarction. Am J Cardiol 1991;68:145-149. 5. Schroeder JS, Lamb IH, Marie Hu MA. Do patients in whom myocardial infarction has beenruled out have a better prognosisafter hospitalization than those surviving infarction? N Engl J iUed 1980; 301:1-5.

Urofcinase Versus Heparin in Acute Myocardial Infarction: No DlffWMW?

Although the results reported by Rossi et al1 suggestthe absenceof a 16-day mortality difference between heparin (control group) and urokinase plus heparin in acute myocardial infarction, the investigators did not discuss adequately some of the factors that may have prevented the demonstration of any underlying difference. The sample size calculation was purportedly basedon an expectedmortality rate of 12% in the control group and a 16.7% reduction in mortality with urokinase (i.e., reduced to 10%). Under these assumptions, a sample size of 3,940 per arm (7,880 total) would provide 80% power at the 2sided 0.05 level, rather than the 1,500 per arm (3,000 total) quoted in this report. A study basedon expected mortality rates of 12 and 10% that only calls for 1,500 patients per arm provides only 39% power. Furthermore, data were only available on a total of 2,201 patients in this study, further reducing the power to 30%. Clinically, the control group included significantly more non-Qwave myocardial infarctions (12.5 vs 8.0%; p = 0.0008). This may have biased the mortality results in favor of the control group. It is wellrecognized that patients with nonQ-wave myocardial infarction have a high incidence of reinfarction and recurrent ischemia during longterm follow up, whereas short-term mortality is about 50% lower than in Q-wave myocardial infarction.* Therefore, it may have been appropriate to prestratify for non-Qwave myocardial infarction. We recognize that the study was initiated in 1985 at a time when in840

formation on dosing regimens for Candela R, Flanagan W, Sasahara A, urokinase in acute myocardial in- Mantel1 S, Lee K, for the TAM1 Study farction was scarce. However, data Group. Evaluation of combinationthromgenerated in subsequentyears sug- bolytic therapy and timing of cardiac gest that Rossi’s regimen was sub- catheterization in acute myocardial inoptimal. Angiographic data and se- farction: results of the Thrombolysis and Angioplasty in Myocardial Infarctionrum fibrinogen levels after throm- Phase 5 Randomized Trial. Circulation bolysis were not presented; such 1991;83:1534-1542. information would have been help- 4. NeuhausK, TebbeU, Gottwik M, Weful in establishing whether the ber M, Feuerer W, Niederer W, Haerer study regimen of 2,000,OOOIU in- W, PraetoriusF, GrosserK-D, Huhmann duced clot lysis and whether a sys- W, Hoepp H-W, Alber G, Sheikhzadeh temic lytic state was present. The A, SchneiderB. Intravenousrecombinant latter is believed to be key to the tissue plasminogen activator and uroprevention of early reocclusion.3 kinase in acute myocardial infarction; results of the German Activator UrokiNeuhaus et al4 showed comparable nase Study. J Am Co11Cardiol 1988;12: go-minute infarct-related artery 581-587. patency rates between recombinant tissue-type plasminogen activator and urokinase, using a 3,000,OOO REPLY: We read with interest the IU doseof urokinase divided equal- comments of Sobolski et al on our ly between a bolus and an infusion article.’ We are very grateful to over 90 minutes. The sameregimen them for elaborating on someof the of urokinase in the Thrombolysis shortcomings of the study. Howand Angioplasty in Myocardial In- ever, we do not believe this correfarction-phase 5 trial3 yielded re- spondenceworth publishing for the sults of equal efficacy when com- following reasons: First, all the pared with that of recombinant tis- points raised in the letter (the same sue-type plasminogen activator in addressedby the reviewers during acute myocardial infarction. the revision process of the paper) In view of the demonstrated im- were adequately and extensively portance of aspirin and heparin in discussedin the article. Second, in effective thrombolysis and mortali- order to highlight the potential dety reduction, it was unfortunate ficiencies of the study, we included that adjunctive therapy with these in the article a detailed limitation agents was not controlled beyond section. We believe that this section 48 hours; the investigators had the put the data into proper perspecoption of continuing not to use, or tive, allowing a better understandto initiate aspirin, oral anticoagu- ing of the importance of the results, lants or subcutaneouscalcium hep- as well as the inconsistenciesof the arin therapy. Such control of these study with regard to other major agents should have been a part of mortality trials. Any other comment on our part the protocol until the observation would be a mere repetition of what period (16 days) was completed. JdWlC.SObdCkl,~PhC was already stated-in our article. Arllwr A. Sauhara, YD Mmmcn McCmnell, MI JamesC.-,m Abbott Park, Illinois 25 September 1991

1. Rossi P, BologneseL, and the USIM Collaborative Group. Comparisonof intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Am J Cardiol 1991;68:585-592. 2. PasternakR, Braunwald E, Sobel B. Acute myocardial infarction. In: Braunwald E, ed. Heart Disease.A Textbook of Cardiovascular Medicine. Philadelphia: Saunders,1988:1222-1313. 3. Califf R, Topol E, Stack R, Ellis S, GeorgeB, KereiakesD, SamahaJ, Worley S, AndersonJ, Harrelson-WoodliefL, Wall T, Phillips H III, Abbottsmith C,

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69

MARCH 15. 1992

Paolo ROSSI,ID Novara, Italy 21 October 1991

Musical Mumlun I have followed with interest the Tucson group’s studies on the origin of Still’s murmur.lv* They have well-documented the ability of dobutamine to increase cardiac output and aortic flow velocity, but the production of Still’s murmur is not documented. I accept their assertion, but question whether there is a causal relation between aortic velocity and Still’s murmur. It seems equally or more likely that the mu-

Urokinase versus heparin in acute myocardial infarction: no difference?

4. GaspozJ-M, Lee TH, Cook EF, Weisberg MC, Goldman L. Outcome of patients who were admitted to a new shortstay unit to “rule-out” myocardial infarcti...
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