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

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  • EDITORIAL

    PCI in ST-elevation infarction / One flew over the cuckoos nestM. DELLBORG

    A prominent proponent of percutaneous coronary

    intervention, PCI, once told me in an educational

    manner that angioplasty is like a cuckoo to a

    hospital budget. Like the cuckoo, it will lays its

    eggs in other birds nest, and push away the other

    eggs and eat up everything there is and the rest of the

    department will famine. PCI is so strong, so

    imperative 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 nests

    of other birds, we still want it around; after all it is

    really nice to hear the typical cuckoo-cuckoo on

    an early summer morning.

    In stable angina, PCI is an excellent treatment. It

    is safe, with very low complication rate, offers good

    symptom relief and may be performed without

    surgical 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 as

    compared to medical therapy, or life-style modifica-

    tion (1,2). For patients with proximal left anterior

    descending-stenosis, surgery with or without pump,

    connecting the internal mammary artery, may be a

    superior alternative. For patients with multivessel

    disease, surgery is still the preferred option with the

    weight of data in favour of surgery as the optimal

    method for long-term relief of angina, providing less

    need of reintervention and probably better survival

    (3).

    For unstable angina/non ST elevation infarction

    (NSTEMI), a policy of revascularization, using

    PCI in about , coronary artery bypass grafting,

    CABG, in of cases and medical therapy in is the

    advocated strategy. This has been challenged by the

    recent ICTUS-trial, sure to initiate a new round of

    discussion (4). ICTUS tells us that with low

    molecular weight heparin, dual antiplatelet treat-

    ment and early high dose statins, we could make

    substantial savings by selecting only patients with

    recurrent ischemia for early revascularization. Any

    survival effect of early revascularization in unstable

    angina/NSTEMI is probably caused by the use of

    by-pass surgery in high-risk patients, as pointed out

    by the authors of the original FRISC-2 publication

    (5).

    For diabetics with stable angina, CABG is the

    prefererred method of revascularization (6). In

    unstable angina/NSTEMI diabetics seem to have

    similar effect with a policy of revascularization in

    general (7), utilizing a mix of PCI and CABG. The

    recent STEMI data from the Danish group suggest

    that thrombolysis is superior to PCI in preventing

    death and particulary recurrent infarction (8).

    PCI has many advantages over medical treatment

    and surgery. It offers good symptom relief, is less

    invasive and conceptually attractive; the patient gets

    the impression he or she has been fixed. The

    major shortcoming of PCI as compared to both

    surgery and medical therapy, is the need for reinter-

    vention. However, with the rapid evolution of

    technology, drug-eluting stents may diminish this

    need but we still lack long-term data in favour of

    drug-eluting stents with respect to mortality.

    However, revascularization remains a sympto-

    matic, palliative treatment for coronary artery dis-

    ease and whatever interventional method used to

    revascularize the patient, the disease is unfortunately

    still present. The flow-limiting stenosis of the

    coronary artery may be dealt with but coronary

    arteriosclerosis is a multi-site, chronic, inflamma-

    tory, progressive disease with acute exacerbations.

    Thus, patients still need to be properly cared for with

    antiplatelets agents, statins, ace-inhibitors, metabolic

    control and life-style modifications. You may have a

    polaroid photograph of your fixed left anterior

    descending in your wallet but you still need to loose

    weight and do your daily 30 minutes of exercise . . .

    Primary PCI for STEMI: the cuckoo of

    cardiology

    In acute ST-elevation infarction, STEMI, the situa-

    tion is even more complex since time until treatment

    becomes vital. The debate between the balloona-

    Scandinavian Cardiovascular Journal. 2006; 40: 8/10

    ISSN 1401-7431 print/ISSN 1651-2006 online # 2006 Taylor & FrancisDOI: 10.1080/14017430500497855

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  • tics and the clotbusters has over the years been

    fierce. Meta-analyses seem to indicate a benefit by

    angioplasty but the problem of publication bias in

    this field is substantial. By now it seems clear that

    thrombolytics are easier to give and can be adminis-

    tered quicker, provide similar effect on mortality and

    has a somewhat higher risk of recurrent MI and

    cerebral bleeding, as compared to angioplasty.

    Angioplasty on the other hand, is clearly very

    expensive, time-delaying and logistically cumber-

    some, necessitates a high degree of centralisation of

    care and has only been clinically tried out in mostly

    low or medium risk patients. Given the large number

    of patients with STEMI (700/800/million popula-tion), the number of patients entered into clinical,

    randomized trials is miniscule. When expanded into

    the real world, patients in their 80s that come in

    with hypotension, left bundlebranch block and

    precordial oppression, tend to end up in the cath

    lab before we use a thermometer and a visual

    inspection of the urine to initiate treatment of the

    urosepsis that brought the patient to the hospital.

    Data from recent studies seem to indicate that a

    policy of direct PCI is superior to a policy of very

    strict thrombolysis with extremely low rates of early

    cross-over (9). One of the problems with the

    DANAMI-2 study is the frequent use of low-

    molecular weight heparin and dual antiplatelet

    treatment in the interventional group, medical

    treatments known to reduce the risk of reinfarction

    and recurrent ischemia (10,11). Since this was the

    major positive effect seen with PCI in the composite

    primary endpoint, this is a serious critique. In a

    similar time but in another country, a policy of very

    early (prehospital) thrombolytic treatment as com-

    pared to transfer for primary angioplasty gave a

    somewhat different result (12). A treatment strategy

    of early thrombolysis with liberal use of PCI for

    recurrent infarction or signs of lytic failure, was

    associated with a reduced mortality in patient that

    could be treated within two hours of onset of

    symptoms (13). For patients that came later, only

    minor differences were seen. In a metaanalysis

    studying in particular the time-difference between

    PCI and lytics, the crucial time-point would be

    60 minutes i.e. a delay of more than 60 minutes from

    lytic to balloon, would favour starting lytics (14).

    However, again, it must be pointed out that funnel-

    plot analysis of published trials of primary PCI vs

    lytics, clearly indicate publications bias. Moderately

    sized studies (200/300 patients) indicating slightfavor for lytics or no difference, seems to remain

    unpublished (15).

    In a previous issue of SCVJ a cost-effective

    analysis is presented, indicating not only a better

    effect of PCI but also lower cost (16). It is an

    attempt to retrospectively rationalize the massive

    economic and logistic focus that has been given to

    establishing PCI as the primary treatment for

    STEMI. This analysis is flawed primarily by severly

    overestimating the results of PCI and including other

    positive effects, established by expert opinion to

    add further, unfounded, enthusiasm regarding the

    effects of PCI vs lytics. In addition, to make the cost

    of keeping a 24 hour cath lab up and running more

    attractive, actual costs are not always included in

    their complex analysis but rather DRG-prizes, and

    prize is very different from cost! Furthermore, this

    analysis as many others, is based on the assumption

    that every patient with STEMI needs to go to the

    cathlab to get a PCI anyway, so why not do it right

    away?! The problem with this line of thinking is that

    it is not supported by data. In the recently published

    Clarity trial, pretreatment with clopidogrel before

    lytics reduced recurrent ischemia, infarction, stroke

    and death. All patients were subject to angiography,

    per protocol. This angiography resulted in PCI being

    performed in just over 55% of those patients but

    almost 40% had no residual, flow-limiting stenosis

    that 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 patients

    do not need early revascularization! This result is

    obtained in a relatively young (B/75 years) popula-tion and it is likely that when applied to older and

    sicker patients, a larger proportion would be suitable

    for CABG, complications with catheterization and

    intervention more common and any long-term

    mortality benefit less likely obtained. Therefore,

    the present analysis or rather mathematical experi-

    ment, is flawed and could and should not serve as a

    basis for medico-political decisions to close down

    smaller hospitals, organize massive transferprograms

    or buy new helicopters.

    In an equally enthusiastic commentary, the retho-

    rical question is asked why primary PCI is not used

    in all countries for all patients (17). The simple

    answer to that is threefold: lack of firm positive

    results in clinical trials, cumbersome logistics when

    applying trial results to clinical care and high cost.

    Interestingly, American guidelines and thinking are

    moving towards more cost-effective and clinically

    effective treatment regimes such as early lytics for

    patients that present within two hours.

    One may debate and discuss these studies in many

    different ways but it seems quite clear that lytics are

    easier and more accessible and have a better effect

    for patients that come very early. This being said, we

    also need to point out that about half of these

    patients will need revascularization within the next

    week and half of those will probably need it within

    the next 24 hours. But at least 40% of them will

    PCI in ST-elevation infarction 9

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  • continue on medical therapy, even if we do an

    angiography before discharge.

    What about the other birds?

    In the last couple of years we have seen dramatic

    results in new areas of acute cardiology that may

    have substantial impact on the cost of cardiological

    care. A growing need for implantable defibrillators,

    ICD, in post-infarction patients, a growing demand

    for resynchronization therapy (CRT) in heartfailure

    and competing demands from related areas such as

    the need for very early treatment of stroke with

    lytics, all increase the need for prioritizing the

    limited resources. Clearly, the situation with the

    same physician performing the diagnostic procedure

    (angiogram), establishing the indication (to dilate or

    not to dilate), doing the procedure and evaluating

    the short-term result (post procedure angiogram) is

    sensitive to criticism. In some medical systems there

    are also strong financial intitiatives that may line up

    in the same direction. As for cardiac surgery,

    cardiologist should be wary of the need to clearly

    establish criteria for and maintain control of the

    referral procedure for PCI as well as for CRT, ICD

    and CABG.

    In conclusion, with the wise combination of lytics,

    lmw heparins and dual antiplatelets with angioplasty

    for recurrent ischemia or lytic failure and with

    primary PCI for cardiogenic shock, contraindication

    for lytics or late arrival, we get most value for money.

    If we restrict the amount of food and room given to

    the cuckoo, the rest of the birds will also survive and

    thrive!

    References

    1. Pitt B, Waters D, Brown WV, van Boven AJ, Schwartz L, Title

    LM, et al. Aggressive lipid-lowering therapy compared with

    angioplasty in stable coronary artery disease. N Engl Med.

    1999;/341:/70/6.2. Hambrecht R, Walther C, Mobius-Winkler S, Gielen S, Linke

    A, Conradi K, et al. Percutaneous coronary angioplasty

    compared with exercise training in patients with stable

    coronary artery disease. A randomized trial. Circulation.

    2004;/109:/1371/8.3. The SOS investigators. Coronary artery bypass surgery versus

    percutaneous coronary intervention with stent implantation in

    patients with multivessel coronary disease (the stent and

    surgery 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 versus

    Conservative Treatment in Unstable Coronary Syndromes

    (ICTUS) Investigators. Early invasive versus selectively in-

    vasive management for acute coronary syndromes. N Engl

    Med. 2005;/353:/1095/104.

    5. FRagmin and Fast Revascularisation during InStability in

    Coronary artery disease Investigators. Invasive compared with

    non-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 Bypass

    Angioplasty 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 factor

    in unstable coronary artery disease even after consideration of

    the 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-2

    Investigators. Does diabetes mellitus abolish the beneficial

    effect of primary coronary angioplasty on long-term risk of

    reinfarction after acute ST-elevation myocardial infarction

    compared 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 fibrinolytic

    therapy 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 as

    Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis

    in Myocardial Infarction (TIMI) 28 Investigators. Effect of

    clopidogrel pre-treatment before percutaneous coronary in-

    tervention in patients with ST-elevation myocardial infarction

    treated 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 28

    Investigators. Addition of clopidogrel to aspirin and fibrino-

    lytic therapy for myocardial infarction with ST-segment

    elevation. N Engl Med. 2005;/352:/1179/89.12. Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden

    EP, Dubien PY, et al., for the Comparison of Angioplasty and

    Prehospital Thromboysis in Acute Myocardial Infarction

    study 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 and

    Prehospital Thrombolysis in Acute Myocardial infarction

    (CAPTIM) Investigators. Impact of time treatment on

    mortality 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 distance

    transport for primary angioplasty vs immediate thrombolysis

    in acute myocardial infarction (PRAGUE-2 trial). E Heart J.

    2003;/24:/1798/9.16. Selmer R, Halvorsen S, Myhre KI, Wisloff TF, Kristiansen

    IS. Cost-effectiveness of primary percutaneous coronary

    intervention versus thrombolytic therapy for acute myocardial

    infarction. Scand Cardiovasc J. 2005;/39:/276/85.17. Clemmensen P, Jurlander B. Primary PCI for ST elevation

    AMI save lives and money / what more do we wnat? ScandCardiovasc J. 2005;/39(5):/264/6.

    10 M. Dellborg

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    este

    r on

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    26/1

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