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• Re: Low usage of coronary stents and adjunctive pharmacotherapy may have influenced the study findin
  Andrew GC Sutton
  Published on: 9 March 2005
• Low usage of coronary stents and adjunctive pharmacotherapy may have influenced the study findings.
  Faizel Osman
  Published on: 1 March 2005

• Published on: 9 March 2005

  Re: Low usage of coronary stents and adjunctive pharmacotherapy may have influenced the study findin

  • Andrew GC Sutton, Consultant Cardiologist
  • Other Contributors:
    • Mark A de Belder, Consultant Cardiologist

  Dear Editor,

  Dr Osman and colleagues are, of course, correct in their comments regarding the evolving nature of percutaneous coronary intervention (PCI) for acute myocardial infarction. However, their comment that the low use of coronary stents, glycoprotein IIb/IIIa inhibition and thienopyridines is likely to have influenced the outcome of our study, and hence our conclusion, is not substantiated by either our...

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  Dear Editor,

  Dr Osman and colleagues are, of course, correct in their comments regarding the evolving nature of percutaneous coronary intervention (PCI) for acute myocardial infarction. However, their comment that the low use of coronary stents, glycoprotein IIb/IIIa inhibition and thienopyridines is likely to have influenced the outcome of our study, and hence our conclusion, is not substantiated by either our own data [1] or by data from other contemporary trials of infarct angioplasty.

  Firstly, plain balloon angioplasty (without stent implantation) was not associated with hospital mortality in our study and neither was lack of treatment with a thienopyridine (both of these variables of course describe the same patient group). PCI without abciximab was also not associated with hospital mortality. The only univariate or multivariate predictors of hospital mortality were those described in the manuscript.

  Secondly, Osman et al. refer to "outcomes" when our study is based on survival in particular. Although stenting confers some advantage, there is currently no evidence that it improves the chance of survival. In the stent-PAMI (Primary Angioplasty in Myocardial Infarction) trial [2], there was no reduction in one month mortality in the group receiving coronary stent(s) compared to those receiving angioplasty alone. In fact, numerically more patients died in the stent arm by one month of follow up (3.5% versus 1.8%, p=0.15). The only significant difference in one month outcomes was in a reduction in target vessel revascularisation in the stent arm (1.3% versus 3.8%, p=0.02). Despite this, there was no difference in the incidence of the combined clinical endpoint of death, reinfarction, disabling stroke or target vessel revascularisation at one month. By six months, the incidence of this composite (primary endpoint) was lower in the stent arm (12.6% versus 20.1%, p<_0.01 almost="almost" exclusively="exclusively" due="due" to="to" less="less" target="target" revascularisation="revascularisation" in="in" the="the" stent="stent" arm="arm" _7.7="_7.7" versus="versus" _17.0="_17.0" p0.001="p0.001" and="and" with="with" a="a" persistent="persistent" numeric="numeric" excess="excess" of="of" deaths="deaths" _4.2="_4.2" _2.7="_2.7" p="p" similarly="similarly" cadillac="cadillac" comparison="comparison" angioplasty="angioplasty" stenting="stenting" or="or" without="without" abciximab="abciximab" acute="acute" myocardial="myocardial" infarction="infarction" trial="trial" _3="_3" incidence="incidence" _30="_30" day="day" mortality="mortality" each="each" four="four" groups="groups" balloon="balloon" alone="alone" was="was" statistically="statistically" same.="same." fact="fact" numerically="numerically" more="more" patients="patients" died="died" _="_" than="than" arm.="arm." these="these" trials="trials" were="were" not="not" powered="powered" detect="detect" early="early" differences="differences" mortality.="mortality."/> Thirdly, the ADMIRAL (Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up) trial [4] in which patients with STEMI were randomised to receive abciximab or placebo prior to primary angioplasty with stenting, demonstrated a statistically significant difference in the incidence of the primary composite endpoint of death, reinfarction, or urgent revascularization of the target vessel at 30 days favouring the abciximab arm (6% versus 14.6%, p=0.01). The trial did not (and could not, because of inadequate power) demonstrate a reduction in mortality at 30 days. Similarly, although Osman cites the trial by Brener et al. [5] for showing clear benefit with the addition of glycoprotein IIb/IIIa inhibition, we must be clear about exactly what those benefits were. There was no benefit in terms of 30 day mortality, nor was there a reduction in the incidence of reinfarction by 30 days. The principle benefit seen by 30 days was a reduction in the incidence in urgent target vessel revascularisation.

  Fourthly, there are no data in the current literature to indicate that the addition of a thienopyridine prior to or after primary PCI for STEMI, in any dose, has any effect on early mortality. The CREDO (Clopidogrel for the Reduction of Events during Observation) trial [6] provides some information on the addition of clopidogrel in patients undergoing contemporary PCI, but these were not patients with STEMI and they were certainly not in cardiogenic shock. There was no statistically significant reduction at 28 days in the incidence of death, MI or target vessel revascularisation in the clopidogrel group compared to placebo (6.8% versus 8.3%, p=0.23) and certainly no mortality benefit. Even amongst those receiving clopidogrel loading more than 6hrs before intervention, there was no significant reduction in mortality. Arbitrarily delaying intervention in cardiogenic shock for such a weak benefit could hardly be justified and none of the patients we treated who were referred from other centres took six hours from referral to the time of angioplasty. It is doubtful whether the paper by Angiolillo et al. [7], in which 50 patients with stable coronary artery disease undergoing elective PCI were randomised to receive either 300mg or 600mg of clopidogrel prior to PCI and underwent assessment of platelet aggregation and activation, is relevant to the current discussion.

  The principle point of interest in our study is whether the presence of particular patient characteristics can be used to determine the likelihood of the natural history of cardiogenic shock complicating acute myocardial infarction being altered by emergency transfer and attempted PCI. Once a catheter-based revascularisation strategy is started, there is very little evidence that procedural or pharmacological "niceties" play a significant role in affecting hospital mortality. Although current patients are likely to receive stents as well as additional anti-platelet agents, we should be clear about what is known and what is not known about these strategies.

  AGC Sutton, MA de Belder

  References

  1. Sutton AGC, Finn P, Hall JA et al. Predictors of outcome after percutaneous treatment for cardiogenic shock. Heart 2005; 91: 339-344.

  2. Grines CL, Cox DA, Stone GW et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Eng J Med 1999;341:1949-56.

  3. Stone GW, Grines CL, Cox DA et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Eng J Med 2002;346:957-66.

  4. Montalescot G, Barragan P, Wittenberg O et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Eng J Med 2001;344:1895-903.

  5. Brener SJ, Barr LA, Burchenal JEB et al. Randomized, placebo- controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734- 741.

  6. Steinhubl SR, Berger PB, Mann JT et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. JAMA 2002; 288(19):2411-20.

  7. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J 2004;25:1903-1910.

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  Conflict of Interest:
  None declared.

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• Published on: 1 March 2005

  Low usage of coronary stents and adjunctive pharmacotherapy may have influenced the study findings.

  • Faizel Osman, SpR in Cardiology
  • Other Contributors:
    • Sohail Qaisar, Nadia El Gaylani

  Dear Editor,

  We read with interest the article by Sutton et al. entitled ‘Predictors of outcome after percutaneous treatment for cardiogenic shock.’ [1]. We would like to congratulate the authors on attempting to identify risk factors that predict outcome in patients with cardiogenic shock who undergo percutaneous coronary intervention (PCI). We would, however, like to make a few points regarding the study that...

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  Dear Editor,

  We read with interest the article by Sutton et al. entitled ‘Predictors of outcome after percutaneous treatment for cardiogenic shock.’ [1]. We would like to congratulate the authors on attempting to identify risk factors that predict outcome in patients with cardiogenic shock who undergo percutaneous coronary intervention (PCI). We would, however, like to make a few points regarding the study that may have influenced its findings.

  The study was conducted between 1995 to 2002 with a total of 113 patients recruited. The use of coronary stents in the study was only 48% and use of abciximab only 25%. Advances in stent technology and increasing evidence from trials on the use of abciximab during PCI suggest that both these treatment options improve outcomes in patients undergoing PCI [2,3]. The use of stents in the study by Sutton et al. is low and probably reflects the fact that stents were not being used routinely for PCI in the mid to late 90’s. Modern management has changed considerably, with stent use in acute myocardial infarction being better than just balloon angioplasty [4]. Along with this trend of increasing stent usage, the use of glycoprotein IIb/IIIa receptor antagonists has also increased with several large trials showing clear benefit of the use of such agents [3]. Evidence also exists for the use of clopidogrel in all patients undergoing PCI, unless contraindicated; emerging data also suggests that the initial loading dose should be 600mg [5]. Sutton et al. only used clopidogrel if one or more stents were used and even then ticlopidine may have been used instead. Less than 50% would therefore have received clopidogrel in this trial and those that did would have received a lower than recommended dose.

  The low use of stents, glycoprotein IIb/IIIa receptor antagonists, and clopidogrel are all likely to have influenced the outcome of the trial and hence the conclusions drawn by the investigators. While we welcome the study and, once again, congratulate the authors on their attempts at identifying those at highest risk of death we would like to point out the limitations of the study in relation to advances in stent and drug use.

  References

  1. Sutton AGC, Finn P, Hall JA, et al. Predictors of outcome after percutaneous treatment for cardiogenic shock. Heart 2005; 91: 339-344.

  2. ACC/AHA guidelines for the management of patients with ST- elevation myocardial infarction-executive summary. Circulation 2003; 110: 588-636.

  3. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734-741.

  4. Schomig A, Ndrepepa G, Mehilli J, et al. A randomized trial of coronary stenting versus balloon angioplasty as a rescue intervention after failed thrombolysis in patients with acute myocardial infarction. J Am Coll Cardiol. 2004; 44 :2073-2079.

  5. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J. 2004; 25: 1903-1910.

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  Conflict of Interest:
  None declared.

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