- Email: [email protected]
Comparison of mortality rates in acute myocardial infarction treated by percutaneous coronary intervention versus fibrinolysis
Comparison of Mortality Rates in Acute Myocardial Infarction Treated by Percutaneous Coronary Intervention Versus Fibrinolysis Amadeo Betriu,
MD,
and Mónica Masotti,
We studied the relation between angioplasty-related time delay and the effectiveness of the intervention in decreasing death compared with fibrinolysis in patients who had acute myocardial infarction. The absolute survival benefit of angioplasty compared with fibrinolysis decreased by 0.24% for every additional 10-minute delay. Regression analysis showed that percutaneous coronary intervention remained superior to fibrinolysis when a time delay related to percutaneous coronary intervention extended to 110 minutes. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:100 –101)
the treatment of ST-segment elevation acute myoinfarction, restoration of coronary blood flow Iat thencardial soonest possible time is critical. Although mechanical reperfusion has been shown to be superior to fibrinolysis, this approach is not universally available and substantial time delays might restrict its benefit. Physicians are frequently faced with a choice between immediate fibrinolysis or, because of a need to prepare a catheterization laboratory or transport a patient to a tertiary center, delayed percutaneous coronary intervention (PCI). Accordingly, we assessed the relation between PCI-related time delay and the effectiveness of this intervention in decreasing death compared with fibrinolysis. In addition, we sought to determine the period of PCI-related delay that might decrease mortality rates equivalent to those with fibrinolysis. •••
We ascertained the relation between time delay and absolute risk difference by using data from 21 of 23 randomized trials included in a quantitative review performed by Keeley et al.1 Two studies from the primary source were excluded because 1 focused on patients who presented with cardiogenic shock2 and another that was published as an abstract had no data on time to treatment. A total of 7,350 patients was assessed, and time from randomization to corresponding treatment (time to balloon inflation and time to needle insertion) was measured. PCI-related time delay was calculated as the difference between median time to balloon inflation with angioplasty and time to needle insertion with fibrinolysis. Benefit was assessed by measuring the difference between mortality rates observed with primary PCI and those observed with fibrinolysis. From the Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain. Dr. Betriu’s address is: Cardiovascular Institute, Hospital Clinic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. E-mail: [email protected]. Manuscript received April 5, 2004; revised manuscript received and accepted August 10, 2004.
100
©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 January 1, 2005
MD
Linear regression was used to assess the relation between PCI-related delay and treatment benefit. Magnitude and statistical significance of the relation were estimated by using weighted least-squares regression, in which results from each trial were weighted by the square root of the number of patients in that trial. Linear regression analysis allowed us to estimate the decrease in benefit for each additional minute of delay in receipt of angioplasty and the delay expected to nullify the initial benefit of PCI. The absolute risk decrease in 4- to 6-week mortality rates with primary PCI as a function of angioplasty-related time delay is shown in Figure 1. Treatment benefit of PCI decreased across trials as time to balloon inflation versus time to needle insertion increased. The absolute survival benefit of angioplasty compared with fibrinolysis decreased by 0.24% for every additional 10-minute delay. Regression analysis showed that mortality rate for angioplasty remained the same to that for fibrinolysis when PCI-related time delay reached 110 minutes. •••
The present analysis suggests that the benefit of primary PCI versus fibrinolysis is substantially decreased with increasing angioplasty-related time delay but on average was maintained when the delay reached 110 minutes. Our findings are in accord with previous observations that indicated that the superiority of mechanical over pharmacologic reperfusion is mitigated when the intervention is delayed.3 Nallamothu and Bates4 stated that the mortality benefit associated with primary PCI ST-segment elevation acute myocardial infarction may be lost if door-toballoon time is delayed ⬎60 minutes compared with fibrinolysis door-to-needle time. Pooled data from 5 control randomized trials5–9 that compared transfer for primary PCI versus fibrinolysis showed that PCI yielded a beneficial survival rate of 2% for a time delay of 65 minutes. Importantly, although these results fit with our findings, they strongly challenge the validity of the linear regression analysis by Nallamothu and Bates.4 Two6,8 of the 21 trials (accounting for 1,050 patients) compared time to balloon inflation with time to reperfusion, which was calculated arbitrarily, by adding 60 minutes to time to needle insertion. For consistency, we systematically measured time to needle insertion in all 21 trials, whereas no correction was applied by Nallamothu and Bates, which certainly accounts for the differences. Several important issues are not reflected in the present analysis. First, increased PCI-related delay is likely to be a marker for poor-quality angioplasty overall; accordingly, the diminished benefit in trials with increas0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.08.069
considerations, one has to be cautious in making inferences from our results.
FIGURE 1. Absolute risk decrease in mortality rates with primary PCI as a function PCI-related time delay.
ing delays may be related not only to the delay itself but also to a number of factors associated with slower, less experienced centers. Second, as with fibrinolysis, the change in the benefit of angioplasty over time from symptom onset might well be nonlinear; as a consequence, a shorter time to equipoise is to be expected for patients who present very early, when the thrombus appears to be more vulnerable to lytic therapy. Third, whether the patient trial means are adequately representative of time delays is questionable. Fourth, a time delay that might nullify the relative advantage of PCI is also affected by the baseline characteristics of the patient and the infarct; therefore, a longer delay could be justified for high-risk patients, although the risks associated with delay may be substantially higher. Because of these
1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13–20. 2. Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999:26;341:625– 634. 3. Kent DM, Lau J, Selker HP. Balancing the benefits of primary angioplasty against the benefits of thrombolytic therapy for acute myocardial infarction: the importance of timing. Eff Clin Pract 2001;4:214 –220. 4. Nallamothu BK, Bates ER. Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything? Am J Cardiol 2003;92:824 – 826. 5. Vermeer F, Oude Ophuis AJ, vd Berg EJ, Brunninkhuis LG, Werter CJ, Boehmer AG, Lousberg AH, Dassen WR, Bar FW. Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study. Heart 1999;82:426 – 431. 6. Widimsky P, Groch L, Zelizko M, Aschermann M, Bednar F, Suryapranata H. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J 2000;21:823– 831. 7. Grines CL, Westerhausen DR Jr, Grines LL, Hanlon JT, Logemann TL, Niemela M, Weaver WD, Graham M, Boura J, O’Neill WW, Balestrini C, for the Air PAMI Study Group. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: the Air Primary Angioplasty in Myocardial Infarction study. J Am Coll Cardiol 2002;39:1713–1719. 8. Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, Branny M, St’asek J, Formanek P, for the ‘PRAGUE’ Study Group Investigators. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial—PRAGUE-2. Eur Heart J 2003;24:94 –104. 9. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, et al, for the DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003;349:733–742.
Effect of Gender on In-Hospital and One-Year Outcomes After Contemporary Coronary Artery Stenting Manish S. Chauhan, MD, Kalon K.L. Ho, MD, MSc, Donald S. Baim, Richard E. Kuntz, MD, MSc, and Donald E. Cutlip, MD Despite the similar extent of epicardial coronary artery disease and procedural success, women have been noted to have a twofold higher incidence of in-hospital mortality and vascular complications than men undergoing coronary artery stenting. This analysis of 1,908 women from a pooled data set of 6,186 patients is the largest reported series of prospectively collected data from the contemporary stent era. This study demonstrates that stenting can be performed in women with excellent acute results with no age-independent increase in short- or long-term mortality compared with men, although with a significantly higher risk of vascular complications. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:101–104) ©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 January 1, 2005
MD,
his study assesses in-hospital and 1-year outcomes after coronary artery stenting in women compared T with men and examines the independent effects of female gender on these outcomes using prospectively collected data from a large cohort of patients from recent multicenter clinical trials. •••
Data of patients enrolled in 6 recent major clinical From the Lahey Clinic Medical Center, Burlington; Harvard Clinical Research Institute, Boston; Beth Israel Deaconess Medical Center, Boston; and Brigham and Women’s Hospital, Boston, Massachsetts. Dr. Chauhan’s address is: Department of Cardiovascular Medicine, Lahey Clinic, 41 Mall Road, Burlington, Massachusetts 01805. Email: [email protected]. Manuscript received April 14, 2004; revised manuscript received and accepted August 12, 2004. 0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.08.070
101
MD,
and Mónica Masotti,
We studied the relation between angioplasty-related time delay and the effectiveness of the intervention in decreasing death compared with fibrinolysis in patients who had acute myocardial infarction. The absolute survival benefit of angioplasty compared with fibrinolysis decreased by 0.24% for every additional 10-minute delay. Regression analysis showed that percutaneous coronary intervention remained superior to fibrinolysis when a time delay related to percutaneous coronary intervention extended to 110 minutes. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:100 –101)
the treatment of ST-segment elevation acute myoinfarction, restoration of coronary blood flow Iat thencardial soonest possible time is critical. Although mechanical reperfusion has been shown to be superior to fibrinolysis, this approach is not universally available and substantial time delays might restrict its benefit. Physicians are frequently faced with a choice between immediate fibrinolysis or, because of a need to prepare a catheterization laboratory or transport a patient to a tertiary center, delayed percutaneous coronary intervention (PCI). Accordingly, we assessed the relation between PCI-related time delay and the effectiveness of this intervention in decreasing death compared with fibrinolysis. In addition, we sought to determine the period of PCI-related delay that might decrease mortality rates equivalent to those with fibrinolysis. •••
We ascertained the relation between time delay and absolute risk difference by using data from 21 of 23 randomized trials included in a quantitative review performed by Keeley et al.1 Two studies from the primary source were excluded because 1 focused on patients who presented with cardiogenic shock2 and another that was published as an abstract had no data on time to treatment. A total of 7,350 patients was assessed, and time from randomization to corresponding treatment (time to balloon inflation and time to needle insertion) was measured. PCI-related time delay was calculated as the difference between median time to balloon inflation with angioplasty and time to needle insertion with fibrinolysis. Benefit was assessed by measuring the difference between mortality rates observed with primary PCI and those observed with fibrinolysis. From the Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain. Dr. Betriu’s address is: Cardiovascular Institute, Hospital Clinic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. E-mail: [email protected]. Manuscript received April 5, 2004; revised manuscript received and accepted August 10, 2004.
100
©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 January 1, 2005
MD
Linear regression was used to assess the relation between PCI-related delay and treatment benefit. Magnitude and statistical significance of the relation were estimated by using weighted least-squares regression, in which results from each trial were weighted by the square root of the number of patients in that trial. Linear regression analysis allowed us to estimate the decrease in benefit for each additional minute of delay in receipt of angioplasty and the delay expected to nullify the initial benefit of PCI. The absolute risk decrease in 4- to 6-week mortality rates with primary PCI as a function of angioplasty-related time delay is shown in Figure 1. Treatment benefit of PCI decreased across trials as time to balloon inflation versus time to needle insertion increased. The absolute survival benefit of angioplasty compared with fibrinolysis decreased by 0.24% for every additional 10-minute delay. Regression analysis showed that mortality rate for angioplasty remained the same to that for fibrinolysis when PCI-related time delay reached 110 minutes. •••
The present analysis suggests that the benefit of primary PCI versus fibrinolysis is substantially decreased with increasing angioplasty-related time delay but on average was maintained when the delay reached 110 minutes. Our findings are in accord with previous observations that indicated that the superiority of mechanical over pharmacologic reperfusion is mitigated when the intervention is delayed.3 Nallamothu and Bates4 stated that the mortality benefit associated with primary PCI ST-segment elevation acute myocardial infarction may be lost if door-toballoon time is delayed ⬎60 minutes compared with fibrinolysis door-to-needle time. Pooled data from 5 control randomized trials5–9 that compared transfer for primary PCI versus fibrinolysis showed that PCI yielded a beneficial survival rate of 2% for a time delay of 65 minutes. Importantly, although these results fit with our findings, they strongly challenge the validity of the linear regression analysis by Nallamothu and Bates.4 Two6,8 of the 21 trials (accounting for 1,050 patients) compared time to balloon inflation with time to reperfusion, which was calculated arbitrarily, by adding 60 minutes to time to needle insertion. For consistency, we systematically measured time to needle insertion in all 21 trials, whereas no correction was applied by Nallamothu and Bates, which certainly accounts for the differences. Several important issues are not reflected in the present analysis. First, increased PCI-related delay is likely to be a marker for poor-quality angioplasty overall; accordingly, the diminished benefit in trials with increas0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.08.069
considerations, one has to be cautious in making inferences from our results.
FIGURE 1. Absolute risk decrease in mortality rates with primary PCI as a function PCI-related time delay.
ing delays may be related not only to the delay itself but also to a number of factors associated with slower, less experienced centers. Second, as with fibrinolysis, the change in the benefit of angioplasty over time from symptom onset might well be nonlinear; as a consequence, a shorter time to equipoise is to be expected for patients who present very early, when the thrombus appears to be more vulnerable to lytic therapy. Third, whether the patient trial means are adequately representative of time delays is questionable. Fourth, a time delay that might nullify the relative advantage of PCI is also affected by the baseline characteristics of the patient and the infarct; therefore, a longer delay could be justified for high-risk patients, although the risks associated with delay may be substantially higher. Because of these
1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13–20. 2. Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999:26;341:625– 634. 3. Kent DM, Lau J, Selker HP. Balancing the benefits of primary angioplasty against the benefits of thrombolytic therapy for acute myocardial infarction: the importance of timing. Eff Clin Pract 2001;4:214 –220. 4. Nallamothu BK, Bates ER. Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything? Am J Cardiol 2003;92:824 – 826. 5. Vermeer F, Oude Ophuis AJ, vd Berg EJ, Brunninkhuis LG, Werter CJ, Boehmer AG, Lousberg AH, Dassen WR, Bar FW. Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study. Heart 1999;82:426 – 431. 6. Widimsky P, Groch L, Zelizko M, Aschermann M, Bednar F, Suryapranata H. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J 2000;21:823– 831. 7. Grines CL, Westerhausen DR Jr, Grines LL, Hanlon JT, Logemann TL, Niemela M, Weaver WD, Graham M, Boura J, O’Neill WW, Balestrini C, for the Air PAMI Study Group. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: the Air Primary Angioplasty in Myocardial Infarction study. J Am Coll Cardiol 2002;39:1713–1719. 8. Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, Branny M, St’asek J, Formanek P, for the ‘PRAGUE’ Study Group Investigators. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial—PRAGUE-2. Eur Heart J 2003;24:94 –104. 9. Andersen HR, Nielsen TT, Rasmussen K, Thuesen L, Kelbaek H, Thayssen P, Abildgaard U, Pedersen F, Madsen JK, Grande P, et al, for the DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003;349:733–742.
Effect of Gender on In-Hospital and One-Year Outcomes After Contemporary Coronary Artery Stenting Manish S. Chauhan, MD, Kalon K.L. Ho, MD, MSc, Donald S. Baim, Richard E. Kuntz, MD, MSc, and Donald E. Cutlip, MD Despite the similar extent of epicardial coronary artery disease and procedural success, women have been noted to have a twofold higher incidence of in-hospital mortality and vascular complications than men undergoing coronary artery stenting. This analysis of 1,908 women from a pooled data set of 6,186 patients is the largest reported series of prospectively collected data from the contemporary stent era. This study demonstrates that stenting can be performed in women with excellent acute results with no age-independent increase in short- or long-term mortality compared with men, although with a significantly higher risk of vascular complications. 䊚2005 by Excerpta Medica Inc. (Am J Cardiol 2005;95:101–104) ©2005 by Excerpta Medica Inc. All rights reserved. The American Journal of Cardiology Vol. 95 January 1, 2005
MD,
his study assesses in-hospital and 1-year outcomes after coronary artery stenting in women compared T with men and examines the independent effects of female gender on these outcomes using prospectively collected data from a large cohort of patients from recent multicenter clinical trials. •••
Data of patients enrolled in 6 recent major clinical From the Lahey Clinic Medical Center, Burlington; Harvard Clinical Research Institute, Boston; Beth Israel Deaconess Medical Center, Boston; and Brigham and Women’s Hospital, Boston, Massachsetts. Dr. Chauhan’s address is: Department of Cardiovascular Medicine, Lahey Clinic, 41 Mall Road, Burlington, Massachusetts 01805. Email: [email protected]. Manuscript received April 14, 2004; revised manuscript received and accepted August 12, 2004. 0002-9149/05/$–see front matter doi:10.1016/j.amjcard.2004.08.070
101