DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction: DECOPI or NOT DECOPI: more smoke on the horizon
H. Achrafi
Former Professor Of Cardiology
Residence Topaze
8 Rue Gd Faubourg
28000 Chartres
France
Tel: +33 23 721 4462
Fax: +33 23 721 4462
E-mail address: hachrafi002{at}rss.fr
The article of Steg et al.1 has intended to determine whether late recanalization of an occluded infarct artery after acute MI is beneficial. Of the 212 patients, the majority had single vessel disease, less than 1/3 had LAD stenosis, and pharmacological therapy was high in both groups. The PTCA success was defined as TIMI flow grade 3 and the follow-up at 6 months included an angiography but the subsequent follow-up comprised clinical evaluation. The conclusion was that At a mean of 34 months of follow-up the occurrence of the primary end point and secondary end point were similar in the medical and the PTCA groups.
We would like to point out several clinical and methodological limitations and the absence of data for accurate evaluation. These limitations have been acknowledged partially by the authors.
- The type II beta error and inadequate power to demonstrate a clinical benefit because of the small sample size of the groups.2
- The selection bias due to the low risk of the population and non-similarity in coronary lesion and MI location. The inclusion of patients with preserved left ventricular ejection fraction (LVEF) might have diluted the benefit of reperfusion.3
- Non-application of the TIMI risk score and the lack of risk-adjusted analyses (age strata, gender, smoking, and so on).
- The absence of a 2x2 factorial design for the assessment of combined efficacy and the interaction of PTCA and medical therapy in this single study.4
- The need to adjust the primary endpoint for multiplicity between groups with the same outcomes for the same patients.5
- The interpretation of secondary endpoint primary endpoint with admission for heart failure which has created a shadow area of uncertainty.6
- The length of this study is also disputable, considering that a sufficient duration is the key factor for quality and cost evaluation when an expensive intervention is compared with drugs therapy.7 The possibility of delayed effects can play a crucial role when patients are randomized to intervention therapy. The PTCA arm may have a negative impact initially because of its invasive nature.
- The absence of gold-standard angiography beyond 6 months and at the time of final result to evaluate the sustained vessel patency. Clinical restenosis can occur in up to 12% of patients after 1 year of follow-up. Even heavily armoured and beefed-up angioplasty with GPIIb/IIIa and drug-eluting stent is not fail-safe and cannot thwart the vexing problem of restenosis.8 The multi-variate analysis of risk factors for restenosis (hypertension, peripheral vessel disease, type C lesion, diabetes, and multi-vessel disease) was absent in this study.
- The inaccuracy of the creatin kinase (CK) as biomarker for peri-procedural events when the current consensus guideline of the joint ESC/ACC advocates the troponins T and I as the best diagnostic test for MI after coronary angioplasty. In contrast to the cytoplasmic enzyme CK and CK-MB, troponins I and T are structural components of the contractile apparatus and have higher discriminatory value in the post-PTCA.
- In taking the TIMI flow grade rather than TIMI perfusion grade as PTCA success, the trialists were looking at the wrong side of the coin and fail short of their goal. Epicardial coronary desobstruction is not synonymous with tissue-level perfusion which can be absent in myocardial region with <15% of blood flow. Muscle viability is strongly linked to the anatomic integrity of microcirculation, which is damaged when coronary occlusion lasted >90 min. Myocardial blush grades studies revealed that the no-reflow phenomenon occurs in up to 30% of the patients with a TIMI flow grade 3 after coronary angioplasty.9
However, angiographic blush grade and even the TIMI frame count are poor indicators of cellular reperfusion when compared with the gold-standard myocardial contrast echography. One can have a TIMI flow grade 3 in angiography, but a TIMI perfusion grade 0 in contrast echography.10 Early measure of coronary flow reserve by transthoracic Doppler is also a safe and useful method in identifying patients at high risk of adverse remodelling and death in spite of successful primary angioplasty. Accelerated de-recruitment of the collateral circulation with a TIMI flow grade 3 but TIMI perfusion grade 0 may pose the patient to high risk of cardiac events.
- Finally, the choice of LVEF as predictive criteria of survival has been challenged by recent studies demonstrating the superiority of new markers such as MVO2max, ESVI, phase-rectified signal analysis, and NT-proBNP.
The forcefrequency relation in a group of patients with similar LVEF during the 5 years of follow-up has shown 30% events when biphasic and 5% events when up-sloping.
In conclusion, the DECOPI trial has not resolved the issue of late reperfusion and unbiased study is needed to promote harmonization and quality in European clinical research. The ongoing study OAT (Occluded Artery Trial), which plans inclusion of 3200 patients 3 to 28 days after MI can help provide the clear evidence to the French popular adage mieux vaut tard que jamais. Until then the cardiologists race against the clock and hunt for clues to deliver desperately needed assistance to survivors of MI.
References
- Steg G, Brucker L, Chevret S et al. DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction. Eur Heart J 2004;25:21872194.[Abstract/Free Full Text]
- Freiman JA, Chalmers TC, Smith HJR et al. The importance of beta, the type II error and sample size in the design and interpretation of the randomized clinical trials. Survey of 17 "negative" trials. N Engl J Med 1978;299:690694.[Abstract]
- Morrison DA, Serruys PW eds. High risk cardiac revascularization and clinical trials.London: Martin Dunitz; 2002.
- McAlister FA, Straus SE, Sackett DL et al. Analysis and reporting of factorial trials: a systematic review. JAMA 2003;289:25452553.[Abstract/Free Full Text]
- Freemantle N, Calvert M, Wood J et al. Composite outcomes in randomized trials, greater precision but with greater uncertainty. JAMA 2003;289:25542559.[Abstract/Free Full Text]
- Freemantle N. Interpreting the results of secondary endpoints and subgroup analysis in clinical trials: should we lock the crazy aunt in the attic? BMJ 2001;322:989991.[Free Full Text]
- Begg C, Chow M, Eastwood S et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996;276:637639.[CrossRef][ISI][Medline]
- Weintraub WS, Kosinski AS, Brown CL III et al. Can restenosis after coronary angioplasty be predicted from clinical variables. Am Coll Cardiol 1993;21:614.[Abstract]
- Henriques JP, Zijlstra F, Van't Hof AW et al. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 2003;107:21152119.[Abstract/Free Full Text]
- Zalewski J, Zmudka K, Tomala M et al. The degree of restored myocardial perfusion in acute infarction influences immediate and long-term results after primary coronary angioplasty. Eur Heart J 2003;304:A1638.