PCI at non-PCI centres: immediate or rescue?

PCI at non-PCI centres: immediate or rescue?

Comment But if the UK is to govern its health system properly, respecting the best international evidence on health systems, being prepared to study ...

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But if the UK is to govern its health system properly, respecting the best international evidence on health systems, being prepared to study its own experiences and learn from them, this kind of political neutering of technical experts needs to end. The President of the Royal College of Surgeons, Bernard Ribeiro, has said there is a “vacuum” of medical input at the Department of Health. Not so. There is a mass of it— a CMO’s office and 14 senior National Clinical Directors at a bare minimum. It is not the quantity of technical input that matters, but its formal nature. That technical input should go well beyond one professional group. Instead of designing a decision-making NHS board, political parties and professional leaders ought to accept that the stewardship of our health system, while it must always be subject to strong lines of political and public accountability, requires independent and transparent technical support and monitoring. There is no case for a decision-making board akin to the monetary policy committee of the Bank of England. But there is certainly a strong case for a technical review panel, much like the Committee on Climate Change established by the 2007 Climate Change Bill. This new technical panel for the UK’s health system would not be a reincarnation of the Standing Medical Advisory Committee, abolished in 2005. It would not be narrowly medical. It would not be a lobbying group for the medical profession’s leaders. Instead, it would make technical recommendations to ministers about health-system priorities, equity, effectiveness, efficiency, trends in demand and supply, and the information

needed to guide good policy making. The technical panel would report to Parliament and have the power to publish its advice. It could investigate any aspect of the health system it deemed in the public interest. And the Secretary of State would have to respond to the panel’s technical advice in Parliament. This technical body would be formally independent of government and it would remain politically neutral. It would not undermine political accountability. Surely the CMO’s office is supposed to provide the independent technical advice ministers need to govern the health system? In clinical and public-health terms, it does, and very effectively too. But a health system needs broader technical advice across economic, social, financial, technological, and scientific domains. The CMO’s remit is too circumscribed to fulfil the role today’s ministers need. Worse, perhaps, the CMO is not truly independent of government. Despite citing obligations to the profession and to the public, the opening words on the CMO’s website are: “I represent the Government, for which I work”. What the UK’s health system needs is the kind of transparent technical advice that puts the interests of its people living in a global context unambiguously first above all other considerations. Richard Horton The Lancet, London NW1 7BY, UK 1 2

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CMO update. London: Department of Health, Winter 2007, issue 46. Dixon A, Alvarez-Rosete A. Governing the NHS: alternatives to an independent board. 2008. http://www.kingsfund.org.uk/publications/ kings_fund_publications/governing_the.html (accessed Feb 11, 2008). Carvel J. Commitment to change. Guardian Jan 9, 2008: 3.

PCI at non-PCI centres: immediate or rescue? See Articles page 559

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Although reperfusion therapy has enormously advanced the care of patients with acute ST-segment-elevation myocardial infarction (STEMI), morbidity and mortality are persistent challenges to investigators. Specifically, the triangle of time from symptom onset, drug regimens, and mechanical intervention has fuelled much research. Because pharmacological reperfusion is easier to give than a primary percutaneous coronary intervention (PCI), the use of a thrombolytic drug remains the most widely used method in many regions, and particularly in developing countries. Even in countries such as France, where catheterisation laboratories are accessible in

nearly all regions, an intravenous thrombolytic drug, usually given in physician-staffed ambulances before admission, is used with excellent clinical results in about 30% of patients.1,2 In today’s Lancet, Carlo Di Mario and colleagues report a trial of half-dose reteplase given with abciximab in patients with STEMI (the CARESS-in-AMI study).3 After being given these drugs, patients were randomly assigned to immediate PCI or to standard treatment, with catheterisation only when rescue PCI was indicated by conventional guidelines. The primary composite outcome was death, reinfarction, or refractory ischaemia www.thelancet.com Vol 371 February 16, 2008

at 30 days.3,4 The trial took place over more than 4 years in more than 60 sites in Poland, Italy, and France, but recruited only 600 of the planned 1800 patients and stopped earlier than planned because of difficulty in recruitment. Before accepting the authors’ conclusion that high-risk patients with STEMI in a non-interventional centre “should be routinely and immediately transferred for PCI” after receiving half-dose reteplase with abciximab, several issues deserve attention. In Di Mario and colleagues’ study, although the primary endpoint achieved statistical significance—ie, a reduction from 32 (10·7%) to 13 (4·4%) events— this estimate has a wide confidence interval (hazard ratio 0·40, 95% CI 0·21–0·76). Although both death and reinfarction seemed less common with systematic PCI than with rescue PCI, the difference was not statistically significant and the overall result was largely modulated by refractory ischaemia, a difficult endpoint to assess in an open-label trial. Moreover the brief duration of unfractionated heparin in the group on standard care and rescue if needed (24 h, or half the duration recommended by US guidelines5), coupled with low use of aspirin and clopidogrel, probably contributed to the striking rise in refractory ischaemia in the first few days after randomisation. Because the drug regimen used was not superior to full-dose reteplase but caused an excess of intracranial haemorrhage in patients older than 75 years in GUSTO V,6 older patients were excluded, thus depriving Di Mario’s trial of the population in whom early complications are the most frequent. Despite this, excess major bleeding occurred in the immediate PCI group and concern about its long-term negative effects is wisely noted. Because the pharmacoinvasive group of CARESS-in-AMI is practically identical to one group (812 patients) in the FINESSE trial, which showed no advantage to this facilitated PCI strategy but more major bleeds than in those treated with primary PCI, it is useful to explore both studies in context. Normal perfusion (ie, TIMI 3 flow) was much higher before PCI in CARESS-in-AMI (61·2%) than in FINESSE (36%).7 The interval between administration of reteplase and abciximab and PCI in CARESS-in-AMI was more than 40 min longer than in FINESSE and might have provided greater opportunity for successful reperfusion. Although the CARESS-in-AMI regimen will probably not be broadly applicable to patients with STEMI, Di Mario and colleagues should be commended www.thelancet.com Vol 371 February 16, 2008

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Coronary angiography

for the excellent cooperation between primary care hospitals and PCI centres that achieved remarkably short times for rescue intervention in the standard-care group (211 min, compared with 135 min in the immediate PCI group). With such organisation (so-called hub and spoke), the results achieved with an intravenous thrombolytic drug given within 12 h of symptom onset and followed by systematic angiography and PCI when possible are excellent (3% 30-day mortality), and are similar to those with primary PCI. These results are in keeping with recent data from the FAST-MI study,1 in which 1-year survival in patients receiving a thrombolytic drug before admission with a 67% rate of PCI in less than 24 h is similar to that with primary PCI, and to those in the Vienna registry when a thrombolytic drug was given within 3 h of symptom onset.8 The timely and frequent rescue, similar to or higher than that found in WEST,9 CAPTIM,10 and REACT,11 probably contributed to the overall low morbidity and mortality in FAST-MI and the Vienna registries. Overall, CARESS-in-AMI suggests, but does not prove, that more liberal use of coronary angiography in a selected population has better results after combined half-dose reteplase and abciximab than does a policy of angioplasty restricted to rescue cases. Moreover, the optimum timing for PCI in this approach is unclear. Before we accept the findings of CARESS-in-AMI we must await results from ongoing studies, including TRANSFER,12 and incorporate additional advances in medical therapy that 535

Comment

decrease the risk of reinfarction and recurrent ischaemia after fibrinolysis. Then we will know whether mechanical intervention beyond rescue in the first 24 h is required for some or all patients with STEMI. Pending these results, organisation of networks to move patients given a thrombolytic drug to institutions with catheterisation laboratories seems a reasonable option, since primary angioplasty cannot be implemented everywhere.13

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*Nicolas Danchin, Paul W Armstrong Department of Coronary Artery Disease and Intensive Care, Hôpital Européen Georges Pompidou Assistance Publique des Hôpitaux de Paris, Université René Descartes, 75015 Paris, France (ND); and Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, AB, Canada (PWA) [email protected]

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ND has received honoraria for speaking from Boehringer Ingleheim, the manufacturer of tenecteplase. PWA has received research grants from Boehringer Ingelheim and Schering Plough and honoraria for speaking from sanofi-aventis and Hoffmann LaRoche.

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Cambou JP, Simon T, Mulak G, Bataille V, Danchin N. The French registry of acute ST elevation or non-ST-elevation myocardial infarction (FAST-MI): study design and baseline characteristics. Arch Mal Coeur Vaiss 2007; 100: 524–34. Danchin N, Blanchard D, Steg PG, et al. Impact of prehospital thrombolysis for acute myocardial infarction on 1-year outcome: results from the French Nationwide USIC 2000 Registry. Circulation 2004; 110: 1909–15. Di Mario C, Dudek D, Piscione F, on behalf of the CARESS-in-AMI (Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction) Investigators. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the combined abciximab reteplase stent study in acute myocardial infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial. Lancet 2008; 371: 559–68.

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Di Mario C, Bolognese L, Maillard L, et al. Combined abciximab reteplase stent study in acute myocardial infarction (CARESS-in-AMI). Am Heart J 2004; 148: 378–85. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51: 210–47. The GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001; 357: 1905–14. Ellis S, for the FINESSE Investigators. The FINESSE trial: Facilitated Intervention with Enhanced Reperfusion. 2007. http://www.cardiologygeneva.ch/FichiersRef/NCardioacademyPFK11-9-07.pdf (accessed Feb 12, 2008). Kalla K, Christ G, Karnik R, for the Vienna STEMI Registry Group. Implementation of guidelines improves the standard of care: the Viennese registry on reperfusion strategies in ST-elevation myocardial infarction (Vienna STEMI registry). Circulation 2006; 113: 2398–405. Armstrong PW, and WEST Steering Committee. A comparison of pharmacologic therapy with/without timely coronary intervention vs. primary percutaneous intervention early after ST-elevation myocardial infarction: the WEST (Which Early ST-elevation myocardial infarction Therapy) study. Eur Heart J 2006; 13: 1530–38. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002; 360: 825–29. Gershlick AH, Stephens-Lloyd A, Hughes S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med 2005; 353: 2758–68. Cantor WJ, Fitchett D, Borgundvaag B, et al. Rationale and design of the trial of routine angioplasty and stenting after fibrinolysis to enhance reperfusion in acute myocardial infarction (TRANSFER-AMI). Am Heart J 2008; 155: 19–25. Labarere J, Belle L, Fourny M, et al. Outcomes of myocardial infarction in hospitals with percutaneous coronary intervention facilities. Arch Intern Med 2007; 167: 913–20.

Excess body fatness: an important cause of most cancers See Articles page 569

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Over the past few decades, the proportions of populations that are overweight (body-mass index [BMI] 25–29·9 kg/m²) or obese (BMI≥30 kg/m²) have been increasing substantially worldwide. This increase is undoubtedly related to changes in lifestyle and diet. Today, about half the adult population in developed countries is classified as overweight or obese.1 Urban populations of some developing countries are approaching similar proportions. In addition to the increase in the risk of cardiovascular disease and type 2 diabetes, excess bodyweight seems to be an important risk factor for some cancers. A recent report by the World Cancer Research Fund and the American Institute for Cancer Research concluded that there is convincing evidence that excess body fat is a cause of oesophageal adenocarcinoma and cancers of the colorectum, pancreas, breast (after menopause), endometrium, and kidney.2

In today’s Lancet, Andrew Renehan and colleagues3 present a systematic review and meta-analysis in which they quantified the risk of cancer associated with increased BMI. The researchers used strict inclusion criteria (only prospective observational studies with incident cancer cases were included), uniform methods and definitions, and sensitivity analyses to compare associations across 20 cancer types and between sexes and populations. Their results (data from 141 articles, 282 137 incident cases) show that a higher BMI is associated with: an increased risk of thyroid, renal, and colon cancers, oesophageal adenocarcinoma, multiple myeloma, leukaemia, and non-Hodgkin lymphoma in both sexes; rectal cancer and malignant melanoma in men; and gallbladder, pancreas, endometrial, and postmenopausal breast cancers in women. The findings are strengthened by heterogeneity and sensitivity analyses which show www.thelancet.com Vol 371 February 16, 2008