PCI in ST-elevation infarction – One flew over the cuckoo's nest

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EDITORIALPCI in ST-elevation infarction / One flew over the cuckoos nestM. DELLBORGA prominent proponent of percutaneous coronaryintervention, PCI, once told me in an educationalmanner that angioplasty is like a cuckoo to ahospital budget. Like the cuckoo, it will lays itseggs in other birds nest, and push away the othereggs and eat up everything there is and the rest of thedepartment will famine. PCI is so strong, soimperative that it tends to push everything else aside,just to make sure it gets enough food and room.Even though the cuckoo may lay its eggs in the nestsof other birds, we still want it around; after all it isreally nice to hear the typical cuckoo-cuckoo onan early summer morning.In stable angina, PCI is an excellent treatment. Itis safe, with very low complication rate, offers goodsymptom relief and may be performed withoutsurgical backup if patients are properly selected.However, in patients with one- or two vessel disease,it may not be better for long-term symptom relief ascompared to medical therapy, or life-style modifica-tion (1,2). For patients with proximal left anteriordescending-stenosis, surgery with or without pump,connecting the internal mammary artery, may be asuperior alternative. For patients with multivesseldisease, surgery is still the preferred option with theweight of data in favour of surgery as the optimalmethod for long-term relief of angina, providing lessneed of reintervention and probably better survival(3).For unstable angina/non ST elevation infarction(NSTEMI), a policy of revascularization, usingPCI in about , coronary artery bypass grafting,CABG, in of cases and medical therapy in is theadvocated strategy. This has been challenged by therecent ICTUS-trial, sure to initiate a new round ofdiscussion (4). ICTUS tells us that with lowmolecular weight heparin, dual antiplatelet treat-ment and early high dose statins, we could makesubstantial savings by selecting only patients withrecurrent ischemia for early revascularization. Anysurvival effect of early revascularization in unstableangina/NSTEMI is probably caused by the use ofby-pass surgery in high-risk patients, as pointed outby the authors of the original FRISC-2 publication(5).For diabetics with stable angina, CABG is theprefererred method of revascularization (6). Inunstable angina/NSTEMI diabetics seem to havesimilar effect with a policy of revascularization ingeneral (7), utilizing a mix of PCI and CABG. Therecent STEMI data from the Danish group suggestthat thrombolysis is superior to PCI in preventingdeath and particulary recurrent infarction (8).PCI has many advantages over medical treatmentand surgery. It offers good symptom relief, is lessinvasive and conceptually attractive; the patient getsthe impression he or she has been fixed. Themajor shortcoming of PCI as compared to bothsurgery and medical therapy, is the need for reinter-vention. However, with the rapid evolution oftechnology, drug-eluting stents may diminish thisneed but we still lack long-term data in favour ofdrug-eluting stents with respect to mortality.However, revascularization remains a sympto-matic, palliative treatment for coronary artery dis-ease and whatever interventional method used torevascularize the patient, the disease is unfortunatelystill present. The flow-limiting stenosis of thecoronary artery may be dealt with but coronaryarteriosclerosis is a multi-site, chronic, inflamma-tory, progressive disease with acute exacerbations.Thus, patients still need to be properly cared for withantiplatelets agents, statins, ace-inhibitors, metaboliccontrol and life-style modifications. You may have apolaroid photograph of your fixed left anteriordescending in your wallet but you still need to looseweight and do your daily 30 minutes of exercise . . .Primary PCI for STEMI: the cuckoo ofcardiologyIn acute ST-elevation infarction, STEMI, the situa-tion is even more complex since time until treatmentbecomes vital. The debate between the balloona-Scandinavian Cardiovascular Journal. 2006; 40: 8/10ISSN 1401-7431 print/ISSN 1651-2006 online # 2006 Taylor & FrancisDOI: 10.1080/14017430500497855Scand Cardiovasc J Downloaded from informahealthcare.com by The University of Manchester on 10/26/14For personal use only.tics and the clotbusters has over the years beenfierce. Meta-analyses seem to indicate a benefit byangioplasty but the problem of publication bias inthis field is substantial. By now it seems clear thatthrombolytics are easier to give and can be adminis-tered quicker, provide similar effect on mortality andhas a somewhat higher risk of recurrent MI andcerebral bleeding, as compared to angioplasty.Angioplasty on the other hand, is clearly veryexpensive, time-delaying and logistically cumber-some, necessitates a high degree of centralisation ofcare and has only been clinically tried out in mostlylow or medium risk patients. Given the large numberof patients with STEMI (700/800/million popula-tion), the number of patients entered into clinical,randomized trials is miniscule. When expanded intothe real world, patients in their 80s that come inwith hypotension, left bundlebranch block andprecordial oppression, tend to end up in the cathlab before we use a thermometer and a visualinspection of the urine to initiate treatment of theurosepsis that brought the patient to the hospital.Data from recent studies seem to indicate that apolicy of direct PCI is superior to a policy of verystrict thrombolysis with extremely low rates of earlycross-over (9). One of the problems with theDANAMI-2 study is the frequent use of low-molecular weight heparin and dual antiplatelettreatment in the interventional group, medicaltreatments known to reduce the risk of reinfarctionand recurrent ischemia (10,11). Since this was themajor positive effect seen with PCI in the compositeprimary endpoint, this is a serious critique. In asimilar time but in another country, a policy of veryearly (prehospital) thrombolytic treatment as com-pared to transfer for primary angioplasty gave asomewhat different result (12). A treatment strategyof early thrombolysis with liberal use of PCI forrecurrent infarction or signs of lytic failure, wasassociated with a reduced mortality in patient thatcould be treated within two hours of onset ofsymptoms (13). For patients that came later, onlyminor differences were seen. In a metaanalysisstudying in particular the time-difference betweenPCI and lytics, the crucial time-point would be60 minutes i.e. a delay of more than 60 minutes fromlytic to balloon, would favour starting lytics (14).However, again, it must be pointed out that funnel-plot analysis of published trials of primary PCI vslytics, clearly indicate publications bias. Moderatelysized studies (200/300 patients) indicating slightfavor for lytics or no difference, seems to remainunpublished (15).In a previous issue of SCVJ a cost-effectiveanalysis is presented, indicating not only a bettereffect of PCI but also lower cost (16). It is anattempt to retrospectively rationalize the massiveeconomic and logistic focus that has been given toestablishing PCI as the primary treatment forSTEMI. This analysis is flawed primarily by severlyoverestimating the results of PCI and including otherpositive effects, established by expert opinion toadd further, unfounded, enthusiasm regarding theeffects of PCI vs lytics. In addition, to make the costof keeping a 24 hour cath lab up and running moreattractive, actual costs are not always included intheir complex analysis but rather DRG-prizes, andprize is very different from cost! Furthermore, thisanalysis as many others, is based on the assumptionthat every patient with STEMI needs to go to thecathlab to get a PCI anyway, so why not do it rightaway?! The problem with this line of thinking is thatit is not supported by data. In the recently publishedClarity trial, pretreatment with clopidogrel beforelytics reduced recurrent ischemia, infarction, strokeand death. All patients were subject to angiography,per protocol. This angiography resulted in PCI beingperformed in just over 55% of those patients butalmost 40% had no residual, flow-limiting stenosisthat could/needed to be treated by catheter intreven-tion (6% of patients were sent to CABG) (11). Thus,after lytic treatment of STEMI, 40% of the patientsdo not need early revascularization! This result isobtained in a relatively young (B/75 years) popula-tion and it is likely that when applied to older andsicker patients, a larger proportion would be suitablefor CABG, complications with catheterization andintervention more common and any long-termmortality benefit less likely obtained. Therefore,the present analysis or rather mathematical experi-ment, is flawed and could and should not serve as abasis for medico-political decisions to close downsmaller hospitals, organize massive transferprogramsor buy new helicopters.In an equally enthusiastic commentary, the retho-rical question is asked why primary PCI is not usedin all countries for all patients (17). The simpleanswer to that is threefold: lack of firm positiveresults in clinical trials, cumbersome logistics whenapplying trial results to clinical care and high cost.Interestingly, American guidelines and thinking aremoving towards more cost-effective and clinicallyeffective treatment regimes such as early lytics forpatients that present within two hours.One may debate and discuss these studies in manydifferent ways but it seems quite clear that lytics areeasier and more accessible and have a better effectfor patients that come very early. This being said, wealso need to point out that about half of thesepatients will need revascularization within the nextweek and half of those will probably need it withinthe next 24 hours. But at least 40% of them willPCI in ST-elevation infarction 9Scand Cardiovasc J Downloaded from informahealthcare.com by The University of Manchester on 10/26/14For personal use only.continue on medical therapy, even if we do anangiography before discharge.What about the other birds?In the last couple of years we have seen dramaticresults in new areas of acute cardiology that mayhave substantial impact on the cost of cardiologicalcare. A growing need for implantable defibrillators,ICD, in post-infarction patients, a growing demandfor resynchronization therapy (CRT) in heartfailureand competing demands from related areas such asthe need for very early treatment of stroke withlytics, all increase the need for prioritizing thelimited resources. Clearly, the situation with thesame physician performing the diagnostic procedure(angiogram), establishing the indication (to dilate ornot to dilate), doing the procedure and evaluatingthe short-term result (post procedure angiogram) issensitive to criticism. In some medical systems thereare also strong financial intitiatives that may line upin the same direction. As for cardiac surgery,cardiologist should be wary of the need to clearlyestablish criteria for and maintain control of thereferral procedure for PCI as well as for CRT, ICDand CABG.In conclusion, with the wise combination of lytics,lmw heparins and dual antiplatelets with angioplastyfor recurrent ischemia or lytic failure and withprimary PCI for cardiogenic shock, contraindicationfor lytics or late arrival, we get most value for money.If we restrict the amount of food and room given tothe cuckoo, the rest of the birds will also survive andthrive!References1. Pitt B, Waters D, Brown WV, van Boven AJ, Schwartz L, TitleLM, et al. Aggressive lipid-lowering therapy compared withangioplasty in stable coronary artery disease. N Engl Med.1999;/341:/70/6.2. Hambrecht R, Walther C, Mobius-Winkler S, Gielen S, LinkeA, Conradi K, et al. Percutaneous coronary angioplastycompared with exercise training in patients with stablecoronary artery disease. A randomized trial. Circulation.2004;/109:/1371/8.3. The SOS investigators. Coronary artery bypass surgery versuspercutaneous coronary intervention with stent implantation inpatients with multivessel coronary disease (the stent andsurgery trial): A randomised controlled trial. Lancet. 2002;/360:/965/70.4. De Winter RJ, Windhausen F, Cornel JH, Dunselman PH,Janus CL, Bendermacher PE, et al., for the Invasive versusConservative Treatment in Unstable Coronary Syndromes(ICTUS) Investigators. Early invasive versus selectively in-vasive management for acute coronary syndromes. N EnglMed. 2005;/353:/1095/104.5. FRagmin and Fast Revascularisation during InStability inCoronary artery disease Investigators. Invasive compared withnon-invasive treatment in unstable coronary-artery disease:FRISC II prospective randomised multicentre study. Lancet.1999;354:708/15.6. The BARI Investigators*. Seven-year Outcome in the BypassAngioplasty Revascularization Investigation (BARI) by Treat-ment and Diabetic Status. J Am Coll Cardiol. 2000;/35:/1122/9.7. Norhammar A, Malmberg K, Diderholm E, Lagerqvist B,Ryden L, Wallentin L. Diabetes mellitus: the major risk factorin unstable coronary artery disease even after consideration ofthe extent of coronary artery disease and benefits of revascu-larization. J Am Coll Cardiol. 2004;43:585/91.8. Madsen MM, Busk M, Sondergaard HM, Bottcher M,Mortensen LS, Andersen HR, et al., for the DANAMI-2Investigators. Does diabetes mellitus abolish the beneficialeffect of primary coronary angioplasty on long-term risk ofreinfarction after acute ST-elevation myocardial infarctioncompared with fibrinolysis? Am J Cardiol. 2005;/96:/1469/75.9. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L,Kelbaek H, Thayssen P, et al, for the DANAMI-2 Investi-gator. A comparison of coronary angioplasty with fibrinolytictherapy in acute myocardial infarction. N Engl Med. 2003;/349:/733/42.10. Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL,Montalescot G, Theroux P, et al., for the Clopidogrel asAdjunctive Reperfusion Therapy (CLARITY)-Thrombolysisin Myocardial Infarction (TIMI) 28 Investigators. Effect ofclopidogrel pre-treatment before percutaneous coronary in-tervention in patients with ST-elevation myocardial infarctiontreated with fibrinolytics. The PCI-CLARITY study. JAMA.2005;/294:/1224/32.11. Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL,Montalescot G, Theroux P, et al, for the CLARITY-TIMI 28Investigators. Addition of clopidogrel to aspirin and fibrino-lytic therapy for myocardial infarction with ST-segmentelevation. N Engl Med. 2005;/352:/1179/89.12. Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFaddenEP, Dubien PY, et al., for the Comparison of Angioplasty andPrehospital Thromboysis in Acute Myocardial Infarctionstudy group. Primary angioplasty versus prehospital fibrino-lysis in acute myocardial infarction: A randomized study.Lancet. 2002;/360:/825/9.13. Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY,Cristofini P, et al., for the Comparison of Angioplasty andPrehospital Thrombolysis in Acute Myocardial infarction(CAPTIM) Investigators. Impact of time treatment onmortality after prehospital fibrinolysis or primary angioplasty.Data from the CAPTIM randomized trial. Circulation. 2003;/108:/2851/6.14. Nallamothu BK, Bates ER. Percutaneous coronary interven-tion versus fibrinolytic therapy in acute myocardial infarction:Is timing (almost) everything. Am J Cardiol. 2003;/92:/824/6.15. Perez de Arenza D, Taneja A, Flather M. Long distancetransport for primary angioplasty vs immediate thrombolysisin acute myocardial infarction (PRAGUE-2 trial). E Heart J.2003;/24:/1798/9.16. Selmer R, Halvorsen S, Myhre KI, Wisloff TF, KristiansenIS. Cost-effectiveness of primary percutaneous coronaryintervention versus thrombolytic therapy for acute myocardialinfarction. Scand Cardiovasc J. 2005;/39:/276/85.17. Clemmensen P, Jurlander B. Primary PCI for ST elevationAMI save lives and money / what more do we wnat? ScandCardiovasc J. 2005;/39(5):/264/6.10 M. DellborgScand Cardiovasc J Downloaded from informahealthcare.com by The University of Manchester on 10/26/14For personal use only.