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Variations between countries in invasive cardiac procedures
CORRESPONDENCE
we have recently initated the third Randomised Intervention Treatment of Angina (RITA-3) trial which is designed to compare interventional and conservative treatment strategies in patients with acute coronary syndromes without persistent ST elevation. Patients assigned to the interventional arm undergo coronary arteriography within 72 h of an index episode of ischaemic chest pain, and the need for revascularisation is determined on clinical grounds. Patients assigned to the conservative strategy are managed medically and undergo coronary arteriography only if criteria for crossover are satisfied. All patients are treated with antiplatelet and antithrombin therapy, and there are no restrictions on the use of glycoprotein IIb/IIIa receptor antagonists or coronary stents. The trial endpoints include the combined rate of death and non-fatal myocardial infarction, symptoms, quality of life, and treatment cost. We invite all UK physicians to consider participation in this important clinical trial. *R A Henderson, D A Chamberlain *Cardiovascular Medicine, University Hospital, Nottingham NG7 2UH, UK and Hove, East Sussex 1
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Yusuf S, Flather M, Pogue J, et al. Variation between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina and myocardial infarction without initial ST elevation. Lancet 1998; 352: 507–14. Topol EJ. What role for catheter laboratories in unstable angina? Lancet 1998; 352: 500–01. Serruys PW, van Hout, B, Bonnier H, et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 1998; 352: 673–81. EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689–96. Boden WE, O’Rourke RA, Crawford MH, et al. Outcomes in patients with acute nonQ-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in hospital (VANQWISH) Trial Investigators. N Engl J Med 1998; 338: 1785–92.
Sir—Salim Yusuf and colleagues’1 conclusion that higher rates of invasive and revascularisation procedures cause no apparent reduction in cardiovascular death or myocardial infarction is based on 7987 patients with presentations covering the gamut of the acute ischaemic syndromes for which thrombolytic therapy is not indicated. As these investigators acknowledge, it would be surprising if concealed within this disparate group
1470
there were not some high-risk subsets for whom an aggressive strategy would improve the outcome. The subset probably at highest risk are patients with evolving infarction who present with primary ST depression.2 Among 227 consecutive patients with infarction presenting with primary ST depression to four UK general hospitals we found a 30-day mortality rate of 30%.3 Subsequent analysis of larger numbers4 showed that patients presenting with ST depression and evolving infarction accounted for about 38% of those with thrombolysisineligible electrocardiograms and 12% of all patients with acute myocardial infarction. Although coronary arteriography was done in only 18% and invasive revascularisation in 7% of the patients, such information as was available from arteriography or necropsy showed that most had threevessel disease. We thought that a much more aggressive strategy towards invasive investigation and treatment was indicated. Although only 17% of OASIS patients developed myocardial infarction, this is still more than 1000 patients, and there must have been several hundred presenting with primary ST depression. Can the investigators separate out these patients from the much larger group whose subsequent course was that of unstable angina, and did variations in invasive procedures affect outcomes in this group? *R M Norris, P S C Wong, for the UK Heart Attack Study investigators Cardiac Department, Royal Sussex County Hospital, Brighton BN2 5BE, UK 1
2
3
4
Yusuf S, Flather M, Pogue J, et al. Variation between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina and myocardial infarction without initial ST elevation. Lancet 1998; 352: 507–14. Lee HS, Cross SJ, Rawles J, Jennings K. Patients with suspected myocardial infarction who present with ST depression. Lancet 1993; 342: 1204–07. Wong PSC on behalf of the United Kingdom Heart Attack Study Group. Acute myocardial infarction presenting with primary ST depression: the need for early intervention. Heart 1996; 75: P50. Wong PSC, El Gaylani N, Griffith K, Dixon G, Robinson DR, Norris RM. The clinical course of patients with acute myocardial infarction who are unsuitable for thrombolytic therapy because of the presenting electrocardiograms. Coronary Artery Dis (in press).
Author’s reply Sir—We appreciate Eric Topol1 and your correspondents’ comments. Evidence for the effects of a therapy can be derived from many sources that
include information from both randomised trials and observational databases. The consistency of all information should be the basis of decision making and decisions should rarely be made on the basis of an individual study. When randomised trials are not available or feasible, appropriately analysed databases can provide some guidance. When the results of both the randomised trial(s) and database analyses are similar, the findings are reinforced and more persuasive. This is exactly the situation here. The VANQWISH trial2 of patients with non-Q wave MI and OASIS registry3 (not the trial, which is separate and conducted subsequently) provide complementary results. Both studies show little benefit in prevention of irreversible major outcomes with a routine or more liberal approach to cardiac catheterisation (followed by interventions based on the coronary anatomy) compared with a more selective approach, whereby only patients with recurrent angina or provokable ischaemia undergo catheterisation. In the usual kinds of analyses, patients who undergo a procedure are compared with those who do not. We did not undertake such an analysis because statistical adjustments cannot be guaranteed appropriately to deal with all the confounders. We chose an ecological approach (by country or by centre) and used standardised entry criteria and outcome definitions and included consecutive patients. Initial presentation to these hospitals within a country, is likely to be determined more by geographic factors than patient characteristics. By having two approaches to such an analysis (across countries and across centres within countries) and observing consistent results, it is unlikely that there was a systemic bias in that patients in all countries (or centres) with high intervention rates were high risk and the others were low risk. Indeed the baseline characteristics in centres with catheterisation laboratories indicated that they were at lower risk, suggesting a subtle shift in the approach to these groups of patients as a whole with more low-risk patients being admitted, followed by more invasive procedures in centres with cardiac catheterisation laboratories compared with centres without such facilities. Like Michael James, we were also surprised and found it illogical that low-risk patients were having cardiac catheterisation more often than high-risk patients. However, this finding has been consistent in several studies5 and is due
THE LANCET • Vol 352 • October 31, 1998
we have recently initated the third Randomised Intervention Treatment of Angina (RITA-3) trial which is designed to compare interventional and conservative treatment strategies in patients with acute coronary syndromes without persistent ST elevation. Patients assigned to the interventional arm undergo coronary arteriography within 72 h of an index episode of ischaemic chest pain, and the need for revascularisation is determined on clinical grounds. Patients assigned to the conservative strategy are managed medically and undergo coronary arteriography only if criteria for crossover are satisfied. All patients are treated with antiplatelet and antithrombin therapy, and there are no restrictions on the use of glycoprotein IIb/IIIa receptor antagonists or coronary stents. The trial endpoints include the combined rate of death and non-fatal myocardial infarction, symptoms, quality of life, and treatment cost. We invite all UK physicians to consider participation in this important clinical trial. *R A Henderson, D A Chamberlain *Cardiovascular Medicine, University Hospital, Nottingham NG7 2UH, UK and Hove, East Sussex 1
2
3
4
5
Yusuf S, Flather M, Pogue J, et al. Variation between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina and myocardial infarction without initial ST elevation. Lancet 1998; 352: 507–14. Topol EJ. What role for catheter laboratories in unstable angina? Lancet 1998; 352: 500–01. Serruys PW, van Hout, B, Bonnier H, et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 1998; 352: 673–81. EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689–96. Boden WE, O’Rourke RA, Crawford MH, et al. Outcomes in patients with acute nonQ-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in hospital (VANQWISH) Trial Investigators. N Engl J Med 1998; 338: 1785–92.
Sir—Salim Yusuf and colleagues’1 conclusion that higher rates of invasive and revascularisation procedures cause no apparent reduction in cardiovascular death or myocardial infarction is based on 7987 patients with presentations covering the gamut of the acute ischaemic syndromes for which thrombolytic therapy is not indicated. As these investigators acknowledge, it would be surprising if concealed within this disparate group
1470
there were not some high-risk subsets for whom an aggressive strategy would improve the outcome. The subset probably at highest risk are patients with evolving infarction who present with primary ST depression.2 Among 227 consecutive patients with infarction presenting with primary ST depression to four UK general hospitals we found a 30-day mortality rate of 30%.3 Subsequent analysis of larger numbers4 showed that patients presenting with ST depression and evolving infarction accounted for about 38% of those with thrombolysisineligible electrocardiograms and 12% of all patients with acute myocardial infarction. Although coronary arteriography was done in only 18% and invasive revascularisation in 7% of the patients, such information as was available from arteriography or necropsy showed that most had threevessel disease. We thought that a much more aggressive strategy towards invasive investigation and treatment was indicated. Although only 17% of OASIS patients developed myocardial infarction, this is still more than 1000 patients, and there must have been several hundred presenting with primary ST depression. Can the investigators separate out these patients from the much larger group whose subsequent course was that of unstable angina, and did variations in invasive procedures affect outcomes in this group? *R M Norris, P S C Wong, for the UK Heart Attack Study investigators Cardiac Department, Royal Sussex County Hospital, Brighton BN2 5BE, UK 1
2
3
4
Yusuf S, Flather M, Pogue J, et al. Variation between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina and myocardial infarction without initial ST elevation. Lancet 1998; 352: 507–14. Lee HS, Cross SJ, Rawles J, Jennings K. Patients with suspected myocardial infarction who present with ST depression. Lancet 1993; 342: 1204–07. Wong PSC on behalf of the United Kingdom Heart Attack Study Group. Acute myocardial infarction presenting with primary ST depression: the need for early intervention. Heart 1996; 75: P50. Wong PSC, El Gaylani N, Griffith K, Dixon G, Robinson DR, Norris RM. The clinical course of patients with acute myocardial infarction who are unsuitable for thrombolytic therapy because of the presenting electrocardiograms. Coronary Artery Dis (in press).
Author’s reply Sir—We appreciate Eric Topol1 and your correspondents’ comments. Evidence for the effects of a therapy can be derived from many sources that
include information from both randomised trials and observational databases. The consistency of all information should be the basis of decision making and decisions should rarely be made on the basis of an individual study. When randomised trials are not available or feasible, appropriately analysed databases can provide some guidance. When the results of both the randomised trial(s) and database analyses are similar, the findings are reinforced and more persuasive. This is exactly the situation here. The VANQWISH trial2 of patients with non-Q wave MI and OASIS registry3 (not the trial, which is separate and conducted subsequently) provide complementary results. Both studies show little benefit in prevention of irreversible major outcomes with a routine or more liberal approach to cardiac catheterisation (followed by interventions based on the coronary anatomy) compared with a more selective approach, whereby only patients with recurrent angina or provokable ischaemia undergo catheterisation. In the usual kinds of analyses, patients who undergo a procedure are compared with those who do not. We did not undertake such an analysis because statistical adjustments cannot be guaranteed appropriately to deal with all the confounders. We chose an ecological approach (by country or by centre) and used standardised entry criteria and outcome definitions and included consecutive patients. Initial presentation to these hospitals within a country, is likely to be determined more by geographic factors than patient characteristics. By having two approaches to such an analysis (across countries and across centres within countries) and observing consistent results, it is unlikely that there was a systemic bias in that patients in all countries (or centres) with high intervention rates were high risk and the others were low risk. Indeed the baseline characteristics in centres with catheterisation laboratories indicated that they were at lower risk, suggesting a subtle shift in the approach to these groups of patients as a whole with more low-risk patients being admitted, followed by more invasive procedures in centres with cardiac catheterisation laboratories compared with centres without such facilities. Like Michael James, we were also surprised and found it illogical that low-risk patients were having cardiac catheterisation more often than high-risk patients. However, this finding has been consistent in several studies5 and is due
THE LANCET • Vol 352 • October 31, 1998