Correspondence

Primary Coronary Angioplasty versus Thrombolysis

N Engl J Med 1997; 337:1168-1170October 16, 1997

Article

To the Editor:

In the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) substudy (June 5 issue),1 although the outcomes at 30 days with primary percutaneous transluminal coronary angioplasty (PTCA) were better than those with accelerated recombinant tissue plasminogen activator (t-PA), the relative reductions in death and reinfarction with PTCA were smaller than in the Primary Angioplasty in Myocardial Infarction (PAMI) trial, the trial in Zwolle, the Netherlands, and the Mayo Clinic trial.2-4 The base-line characteristics of the patients enrolled in these trials were similar to those of the patients enrolled in GUSTO IIb,1-4 as were the outcomes in the patients treated with thrombolysis (Figure 1Figure 1Short-Term Outcomes in the Main Randomized Trials of Reperfusion.The analysis is based on the following numbers of patients: for thrombolytic therapy, 405 in the PAMI, Zwolle, and Mayo Clinic trials and 573 in the GUSTO IIb trial; for primary PTCA, 394 in the PAMI, Zwolle, and Mayo Clinic trials and 565 in the GUSTO IIb trial.). The use of front-loaded t-PA therefore does not explain the differences in results.

Instead, poorer-than-expected procedural outcomes in the GUSTO IIb trial directly resulted in higher numbers of deaths and reinfarctions among the patients treated with primary PTCA. As compared with the patients assigned to angioplasty in the earlier trials, those assigned to PTCA in the GUSTO IIb trial were less likely to undergo immediate angiography (100 percent vs. 94 percent, P<0.001) and angioplasty (91 percent vs. 81 percent, P<0.001). Since the primary end point of death, reinfarction, or nonfatal disabling stroke was strikingly less frequent in the GUSTO IIb trial if angioplasty was performed than if it was not performed (6.7 percent vs. 20.7 percent), this difference alone may account for much of the disparity. Furthermore, a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was restored in only 73 percent of the patients treated with angioplasty in the GUSTO IIb trial, as compared with 94 percent of those treated with angioplasty in the other trials (P<0.001). This difference cannot be attributed to the lack of core laboratories in the earlier studies, as stated in the GUSTO IIb report; all three earlier trials used core laboratories directed by physicians not involved in patient enrollment, as did GUSTO IIb. We have previously shown that the restoration of a TIMI grade 3 flow is the strongest determinant of short-term survival after any reperfusion therapy.5 This was confirmed in GUSTO IIb, since the 30-day mortality after PTCA was 1.6 percent if a TIMI grade 3 flow was restored, as compared with 20.0 percent with a TIMI grade of 0 through 2. The low rate of procedural success in GUSTO IIb probably also explains why high-risk patients did not preferentially benefit from PTCA and why the late benefit was attenuated, in contrast to the results of the other studies.2,3

The sites participating in the GUSTO IIb trial were chosen if they met minimal standards for elective angioplasty, as recommended by the American College of Cardiology. No information is given about their experience with or commitment to primary PTCA. In contrast, the sites participating in the PAMI, Zwolle, and Mayo Clinic trials were all experienced centers dedicated to primary PTCA. The main lesson from the GUSTO IIb trial is that even at inexperienced centers, primary PTCA, as compared with any current thrombolytic regimen, will virtually eliminate intracranial bleeding, reduce recurrent ischemia and prevent unplanned revascularization procedures, shorten the hospital stay, and improve short-term survival free of reinfarction, and at dedicated centers, primary PTCA will result in markedly improved early and late event-free survival.

Gregg W. Stone, M.D.
El Camino Hospital, Mountain View, CA 94040

Cindy L. Grines, M.D.
William W. O'Neill, M.D.
William Beaumont Hospital, Royal Oak, MI 48073

5 References

1. 1

   The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621-1628
   Full Text | Web of Science | Medline

2. 2

   Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673-679
   Full Text | Web of Science | Medline

3. 3

   de Boer MJ, Hoorntje JC, Ottervanger JP, Reiffers S, Suryapranata H, Zijlstra F. Immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: left ventricular ejection fraction, hospital mortality and reinfarction. J Am Coll Cardiol 1994;23:1004-1008
   CrossRef | Web of Science | Medline

4. 4

   Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993;328:685-691
   Full Text | Web of Science | Medline

5. 5

   Stone GW, O'Neill WW, Jones D, Grines CL. The central unifying concept of TIMI-3 flow after primary PTCA and thrombolytic therapy in acute myocardial infarction. Circulation 1996;94:Suppl I:I-515 abstract.
   

To the Editor:

The GUSTO IIb trial compared primary PTCA with front-loaded t-PA in the treatment of acute myocardial infarction. Although primary PTCA is the best way to achieve prompt and complete recanalization of the infarct-related artery, the results of the trial showed only a mild-to-moderate improvement in the clinical outcome with PTCA. Indeed, since patients with acute myocardial infarction receiving thrombolytic therapy have, on average, quite a good prognosis (30-day mortality, 7.0 percent in the t-PA group),1 it is unlikely that new treatments administered to unselected patients could yield a remarkable survival benefit. It is worth noting that front-loaded t-PA has optimal results in most patients, resulting in complete reperfusion (a TIMI grade 3 flow) in about 56 percent of patients.2 In such patients, PTCA cannot yield an additional benefit, as compared with thrombolysis, apart from preventing intracranial hemorrhage.

A better strategy may be the identification of subgroups of patients who have an adverse prognosis with standard treatment. Patients with thrombotic occlusions and less atherosclerosis may have good responses to thrombolytic therapy, whereas in patients with deep plaque ulcerations and plaque hemorrhages, recanalization may be achieved only with primary PTCA. Indeed, recent studies have shown that simple clinical data may help identify these different groups of patients.3 A substudy of the PAMI trial showed that nonsmokers have a significant benefit from PTCA, whereas smokers (who are known more often to have a thrombotic occlusion of a smaller atherosclerotic lesion) have the same results with PTCA and thrombolytic therapy.4 Furthermore, the occurrence of unstable angina during the week before the acute myocardial infarction has been associated with a more rapid response to thrombolytic therapy and to a smaller infarct size.5 These findings suggest that new trials should be designed to test the effects of PTCA in selected groups of patients, who may benefit the most from this more aggressive, and expensive, treatment.

Vincenzo Pasceri, M.D.
Università Cattolica del Sacro Cuore, 00168 Rome, Italy

5 References

1. 1

   The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621-1628
   Full Text | Web of Science | Medline

2. 2

   The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615-1622[Erratum, N Engl J Med 1994;330:516.]
   Full Text | Web of Science | Medline

3. 3

   Pasceri V, Andreotti F, Maseri A. Clinical markers of thrombolytic success. Eur Heart J 1996;17:Suppl E:35-41
   Web of Science | Medline

4. 4

   Bowers TR, Terrien EF, O'Neill WW, Sachs D, Grines CL. Effect of reperfusion modality on outcome in nonsmokers and smokers with acute myocardial infarction (a Primary Angioplasty in Myocardial Infarction [PAMI] substudy). Am J Cardiol 1996;78:511-515
   CrossRef | Web of Science | Medline

5. 5

   Andreotti F, Pasceri V, Hackett DR, Davies GJ, Haider AW, Maseri A. Preinfarction angina as a predictor of more rapid coronary thrombolysisin patients with acute myocardial infarction. N Engl J Med 1996;334:7-12
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Representatives of the PAMI study group note the difference between the modest benefit of PTCA, as compared with t-PA, in the GUSTO IIb trial and the greater benefit of angioplasty noted in the PAMI and Zwolle trials, attributing much of the difference to the experience with angioplasty and technical results of the physician operators. Elsewhere, these investigators have contended that operator experience and institutional volume do not influence the outcome of primary angioplasty.1 There is, however, ample evidence that highly experienced interventionalists and higher-volume hospitals achieve superior results with angioplasty, in general, than their lower-volume counterparts. There is no reason to believe that if sufficient numbers of patients and physicians were studied, the results of angioplasty for infarction would not be shown to have a similar volume–outcome relation. However, the GUSTO sites' experience is far more representative of (and in fact, exceeds) the overall experience of U.S. centers than that of the PAMI group, and recent reports from the Myocardial Infarction Triage and Intervention Project registry 2 and even less experienced groups3 underscore the danger of extrapolating the results of centers with particular expertise in primary angioplasty to the cardiology community at large.

That being acknowledged, investigators from experienced angiographic core laboratories recognize the difficulties in comparing TIMI grades between core laboratories.4 Although the restoration of “normal flow” may be an appropriate end point for two or more treatments studied by a single core laboratory, interlaboratory differences in the assessment of a TIMI grade 3 flow with the same treatment commonly vary by as much as 10 to 20 percent. The core laboratory used by the GUSTO study group is known to be conservative in assigning a TIMI grade 3.4 It would be of interest to know what established and recognized core laboratory analyzed the TIMI grade for the studies Stone et al. cite. The disparity in TIMI grade 3 flow rates for primary angioplasty in the GUSTO and PAMI trials may well be overstated. Virtually all major core laboratories now also record a more objective method of assessing flow, the corrected TIMI frame count.

The PAMI group representatives also seek to minimize the potential importance of the thrombolytic agent used for comparison. This is an oversimplification. As might be expected from the results of GUSTO I, a meta-analysis of all randomized trials of primary angioplasty compared with thrombolytic therapy for acute myocardial infarction suggests a graded relative benefit of angioplasty that is dependent on the thrombolytic regimen used. Weaver et al. report a 30 percent reduction in death and nonfatal reinfarction for angioplasty when accelerated t-PA was used as the thrombolytic regimen, a 49 percent reduction when the original three-hour t-PA dosing was used, and a 59 percent reduction when streptokinase was used.5

Stephen G. Ellis, M.D.
Eric J. Topol, M.D.
Cleveland Clinic Foundation, Cleveland, OH 44195

Amadeo Betriu, M.D.
Universitat de Barcelona, 08036 Barcelona, Spain

Robert M. Califf, M.D.
Duke University Medical Center, Durham, NC 27710

5 References

1. 1

   O'Neill WW, Griffin JJ, Stone G, et al. Operator and institutional volume do not affect the procedural outcome of primary angioplasty therapy. J Am Coll Cardiol 1996;27:Suppl A:13A-13A abstract.
   CrossRef

2. 2

   Every NR, Parsons LS, Hlatky M, Martin JS, Weaver WD. A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. N Engl J Med 1996;335:1253-1260
   Full Text | Web of Science | Medline

3. 3

   Jhangiani AH, Jorgensen MB, Kotlewski A, Mansukhani PW, Aharonian VJ, Mahrer PR. Community practice of primary angioplasty for myocardial infarction. Am J Cardiol 1997;80:209-212
   CrossRef | Web of Science | Medline

4. 4

   Ross AM, Neuhaus K-L, Ellis SG. Frequent lack of concordance among core laboratories in assessing TIMI flow grade after reperfusion therapy. Circulation 1995;92:Suppl 1:I-718 abstract.
   

5. 5

   Weaver WD, Simes RJ, Betriu A, et al. Primary coronary angioplastyvs. intravenous thrombolysis for treatment of acute myocardial infarction: a quantitative overview of their comparative effectiveness. JAMA (in press).
   

Citing Articles (5)

Citing Articles

1. 1

   Surinder P. Janda, Nicholas Tan. (2009) Thrombolysis versus primary percutaneous coronary intervention for ST elevation myocardial infarctions at Chilliwack General Hospital. Canadian Journal of Cardiology 25:11, e382-e384
   CrossRef

2. 2

   Ekrem Yeter, Ali E Denktas. (2009) Prehospital fibrinolytic therapy followed by urgent percutaneous coronary intervention in patients with ST-elevation myocardial infarction. Future Cardiology 5:4, 403-411
   CrossRef

3. 3

   Ellis, Stephen G., Tendera, Michal, de Belder, Mark A., van Boven, Ad J., Widimsky, Petr, Janssens, Luc, Andersen, H.R., Betriu, Amadeo, Savonitto, Stefano, Adamus, Jerzy, Peruga, Jan Z., Kosmider, Maciej, Katz, Olivier, Neunteufl, Thomas, Jorgova, Julia, Dorobantu, Maria, Grinfeld, Liliana, Armstrong, Paul, Brodie, Bruce R., Herrmann, Howard C., Montalescot, Gilles, Neumann, Franz-Josef, Effron, Mark B., Barnathan, Elliot S., Topol, Eric J., . (2008) Facilitated PCI in Patients with ST-Elevation Myocardial Infarction. New England Journal of Medicine 358:21, 2205-2217
   Full Text

4. 4

   Maurizio Menichelli, Antonio Parma, Edoardo Pucci, Rosario Fiorilli, Francesco De Felice, Marco Nazzaro, Alessia Giulivi, Domenico Alborino, Arianna Azzellino, Roberto Violini. (2007) Randomized Trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI). Journal of the American College of Cardiology 49:19, 1924-1930
   CrossRef

5. 5

   Anne Kaltoft, Morten Bøttcher, Lars Krusell, Leif Thuesen, Steen Dalby Kristensen, Henning Rud Andersen, Torsten Toftegaard Nielsen. (2002) Establishing Primary Angioplasty as the Preferred Treatment for Acute Myocardial Infarction. Scandinavian Cardiovascular Journal 36:4, 215-220
   CrossRef