Optimal Duration of Dual Antiplatelet Therapy After DES Implantation: A Meta-Analysis of 11 Randomized Trials
Angiology 1-15 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715586500 ang.sagepub.com
Monica Verdoia, MD1, Alon Schaffer, MD1, Lucia Barbieri, MD1, Gilles Montalescot, MD2, Jean-Philippe Collet, MD2, Antonio Colombo, MD3, Harry Suryapranata, MD4, and Giuseppe De Luca, MD, PhD1
Abstract Despite new-generations of drug-eluting stents (DESs), the optimal duration of dual antiplatelet therapy (DAPT) remains controversial. We performed a meta-analysis of randomized trials (RTs) evaluating the effectiveness and safety of shorter versus longer DAPT duration strategies in patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched. The primary end point was mortality. Secondary end points were (1) cardiovascular mortality, (2) nonfatal myocardial infarction, (3) definite/probable stent thrombosis (ST), and (4) major bleedings. We included 11 RTs (n ¼ 32 372 patients). Shorter DAPT duration reduced mortality (odds ratio, OR [95% confidence interval, CI] ¼ 0.85 [0.71-1], P ¼ .05; p heterogeneity ¼ 0.91). Similar results were observed when comparing 3 to 6 versus 12 months DAPT, while a significant increase in recurrent ischemic events was found for 6 to 12 months DAPT versus extended treatment (myocardial infarction: OR [95%CI] ¼ 1.66 [1.37-2], P < .00001; phet ¼ 0.13 and ST: OR [95%CI] ¼ 2.47 [1.72-3.45], P < .00001; phet ¼ 0.12), however, counterbalanced by a significant reduction in major bleeding (OR [95%CI] ¼ 0.60 [0.470.76], P < .0001; phet ¼ 0.38) and a trend in lower mortality. Thus, among selected patients undergoing DES implantation, a shorter DAPT strategy is associated with reduction in mortality and major bleeding but a higher risk of myocardial infarction and ST. A short duration (3-6 months) of DAPT appears as the safest strategy, while a prolonged duration (24-36 months) reduces thrombotic complications but with an excess in major bleeding complications. Keywords dual antiplatelet therapy, duration, drug-eluting stents, meta-analysis
Background Optimal platelet inhibition is a key issue in the treatment of patients undergoing percutaneous coronary interventions (PCIs) and especially in the era of drug-eluting stents (DESs).1 The introduction of new, more potent antiplatelet agents and the identification of patients with high residual platelet reactivity led to better short- and long-term clinical outcomes of patients with coronary artery disease.2-4 Still debated is the ideal duration of dual antiplatelet therapy (DAPT) after coronary stenting, especially after the introduction of second-generation DES, associated with a consistent reduction in stent thrombosis (ST) as compared with first-generation DES.5 A reduced DAPT duration could be considered safe, and also effective, reducing the risk of bleeding complications, which have been demonstrated to impact on mortality.6 On the other hand, very late (>12 months) ST reported after DES implantation suggests that DAPT may be extended beyond the recommended duration of 6 to 12 months.7
Several studies have been conducted so far to define the optimal duration of DAPT after DES implantation. However, they were not powered enough to evaluate hard end points such as mortality and ST and therefore could not provide any conclusive recommendation for the optimal timing of DAPT discontinuation after DES implantation.8 Therefore, the aim of the present meta-analysis was to compare the effectiveness in
1
Division of Cardiology, Azienda Ospedaliera-Universitaria ‘‘Maggiore della Carita`,’’ Eastern Piedmont University, Novara, Italy 2 Institut de Cardiologie, Centre Hospitalier Pitie´-Salpeˆtrie`re (AP-HP, ACTION Group, University Paris 6), Paris, France 3 Interventional Cardiology Unit, San Raffaele Scientific Institute and EMOGVM Centro Cuore Columbus, Milan, Italy 4 Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands Corresponding Author: Giuseppe De Luca, Azienda Ospedaliera-Universitaria ‘‘Maggiore della Carita`,’’ Eastern Piedmont University, Corso Mazzini, 18, Novara 28100, Italy. Email: [email protected]
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
2
Angiology
terms of mortality and bleeding complications of a shorter DAPT strategy versus an extended DAPT strategy in patients undergoing DES implantation.
2209 records idenfied by lierature search
6 addional unpublished records idenfied by manual search
2142 citaons excluded in case of: 1) not full –lenght arcles; 2) no original data; 3) meta-analysis
Methods Eligibility and Search Strategy The literature was scanned by formal searches of electronic databases (MEDLINE, Cochrane, and EMBASE) for clinical studies and furthermore the scientific session abstracts searched on the ‘‘TCT’’ (www.tctmd.com), ‘‘EuroPCR’’ (www.europcr.com), American College of Cardiology (ACC; www.acc.org), American Hospital Association (AHA; www. aha.org), and European Society of Cardiology (ESC; www. escardio.org) Web sites, for oral presentations and/or expert slide presentations from January 1990 to November 2014. The following key words were used: ‘‘dual antiplatelet therapy,’’ ‘‘clopidogrel,’’ ‘‘ticagrelor,’’ ‘‘prasugrel,’’ ‘‘duration,’’ ‘‘drugeluting stent,’’ ‘‘DES,’’ ‘‘randomized.’’ No language restrictions were enforced. Inclusion criteria were (1) patients undergoing PCI with stent implantation, (2) availability of complete clinical data, and (3) randomized treatment allocation. Exclusion criteria were (1) follow-up data in less than 90% of patients and (2) ongoing studies or irretrievable data.
Data Extraction and Validity Assessment Data were independently abstracted by 2 investigators (MV and AS). In case of incomplete or unclear data, the authors were contacted. Disagreements were resolved by consensus. Data were managed according to the intention-to-treat principle. Data on cardiovascular mortality were collected if data on overall mortality were not available.
Outcome Measures Primary end point was overall mortality. Secondary end points were (1) cardiovascular mortality, (2) recurrent myocardial infarction, and (3) ST (definite or probable according to Academic Research Consortium definition). Safety end point was the rate of major bleeding complications (according to protocol definition).
Data Analysis Statistical analysis was performed using the Review Manager 4.27 freeware package, SPSS 17.0 statistical package. Odds ratio (OR) and 95% confidence intervals (95%CI) were used as summary statistics. The pooled OR was calculated using a fixed effect model (Mantel-Haensel). The Breslow-Day test was used to examine the statistical evidence of heterogeneity across the studies (P < .1). Potential publication bias was examined by constructing a ‘‘funnel plot,’’ in which sample size was plotted against ORs (for the primary end point). The study quality was evaluated by the same 2 investigators according to a score, which was expressed on a ordinal scale, allocating 1
73 full-lenght arcles assessed for elegibility
13 randomized trials inially idenfied
60 studies excluded aer inclusion/exclusion criteria applicaon (outcome endpoints, randomized design, treatment compleon >90% of study populaon) 2 trials excluded because were duplicates
11 randomized trials included in final meta-analysis
Figure 1. Flow diagram of the systematic overview process.
point for the presence of each of the following: (1) statement of objectives, (2) explicit inclusion and exclusion criteria, (3) description of intervention, (4) objective means of follow-up, (5) description of adverse events, (6) power analysis, (7) description of statistical methods, (8) multicenter design, (9) discussion of withdrawals, and (10) details on medical therapy. A prespecified analysis was performed according to the type of trial (trials comparing DAPT 12 months; 3.1% [281 of 9270] vs 1.8% [171 of 9357], OR [95%CI] ¼ 1.66 [1.37-2], P < .00001; phet ¼ 0.13), whereas similar results were obtained between the 2 treatment groups in trials on short-term DAPT (3-6 months with 12 months; 1.6% [98 of 5963] vs 1.5% [93 of 5992], OR [95%CI] ¼ 1.06 [0.80-1.42], P ¼ .67, phet ¼ 0.65, P interaction ¼ .01). Stent thrombosis. Data on definite/probable ST were available in 30 582 (94.4%) patients (1 study16 evaluated only definite ST). A total of 188 (0.6%) patients experienced such an event. The risk of ST was significantly doubled with shorter versus longer DAPT duration (0.8% [126 of 15 233] vs 0.4% [62 of 15 349], OR [95%CI] ¼ 2.04 [1.52-2.75], P < .00001; phet ¼ 0.12, Figure 6). The results were mainly driven by a significant benefit in ST from extended (beyond 1 year) DAPT duration (12 to >12 months; 1.1% [101 of 9495] vs 0.4% [41 of 9594], OR [95%CI] ¼ 2.47 [1.72-3.55], P < .00001; phet ¼ 0.12), while no significant difference was observed in trials on short DAPT duration (3-6 vs 12 months; 0.5% [29 of 5963] vs 0.4% [23 of 5992], OR [95%CI] ¼ 1.27 [0.73-2.19], P ¼ .40; phet ¼ 0.59, P interaction ¼ .05). Safety end point. Data on major bleedings were available in 10 studies including 30 400 (92.9%) patients, of whom 339 (1.1%) patients experienced such an event. Thrombolysis in myocardial infarction major definition was used in 7 studies.8,10,12,14,16,17,19 As displayed in Figure 7, shorter DAPT duration significantly reduced the rate of major bleeding events (0.8% [127 of 15 145] vs 1.4% [212 of 15 255], OR [95%CI] ¼ 0.61 [0.49-0.76], P < .00001; phet ¼ 0.86). The reduction in bleeding events was significant in trials evaluating extended DAPT duration (12 vs > 12 months; 1.2% [104 of 9182] vs 1.9% [179 of 9263], OR [95%CI] ¼ 0.60 [0.47-0.76], P < .0001; phet ¼ 0.38), while trials evaluating short DAPT duration showed a consistent and similar trend as indicated by the OR and the interaction value (3-6 vs 12 months; 0.4% [23 of 5963] vs 0.6% [33 of 5992], OR [95%CI] ¼ 0.70 [0.41-1.20], P ¼ .19, phet ¼ 0.99, P interaction ¼ .59).
Discussion The present study represents the largest meta-analysis of RTs comparing the safety and efficacy in terms of ischemic and bleeding complications of different DAPT duration strategies in patients undergoing percutaneous coronary revascularization with DES. Our meta-analysis showed that among patients undergoing DES implantation, a shorter DAPT duration is safer and associated with a significant reduction in overall mortality, a significant reduction in major bleeding, but associated with higher risk of late thrombotic complications, including ST.
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
4
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
RESET
EXCELLENT
Study
2012
2012
Publication
Multicenter, RCT
Multicenter, RCT
Type
ASA þ clopidogrel
ASA þ clopidogrel
Strategy Shorter DAPT
Table 1. Characteristics of Included Randomized Studies.
3
6
Months
ASA þ clopidogrel
ASA þ clopidogrel
Strategy Longer DAPT
Antiplatelet Treatment
12
12
Months
8.
7.
6.
4. 5.
2. 3.
1.
Coronary artery disease including stable angina, unstable angina, and acute myocardial infarction. Age 20 years or older. Typical chest pain and objective evidences of myocardial ischemia on the electrocardiogram or positive functional studies consistent. Signed informed consent. Significant coronary artery stenosis (>50% by visual estimate), which is considered for coronary revascularization with stent implantation. Reference vessel diameter of 2.5 to 4.0 mm by the visual estimation of operator assessment. Lesion success (30% or less residual stenosis by visual assessment over the entire stent length, with thrombolysis in myocardial infarction [TIMI]-3 flow and no more than type B peristent dissection in National Heart, Lung, and Blood Institute [NHLBI] criteria). Lesion and stent length for shortlesion subgroup: (1) length of single stent per single lesion 24 mm and (2) summation of total length of all
1. One lesion in a native coronary vessel with a reference diameter of 2.25 to 4.25 mm. 2. Stenosis of 50% by visual estimation and evidence of myocardial ischemia such as stable angina, unstable angina, recent myocardial infarction, silent ischemia, a positive functional study, or reversible changes in ECG consistent with ischemia. 3. Documentation of ischemia was not mandatory for lesions with 75% stenosis.
Inclusion
12.
10. 11.
7. 8. 9.
6.
5.
4.
3.
2.
13. 1.
11. 12.
10.
9.
8.
6. 7.
5.
4.
3.
1. 2.
10
10
Quality Score
(continued)
Myocardial infarction within 72 h. Severely compromised ventricular dysfunction (ejection fraction
Angiology 1-15 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715586500 ang.sagepub.com
Monica Verdoia, MD1, Alon Schaffer, MD1, Lucia Barbieri, MD1, Gilles Montalescot, MD2, Jean-Philippe Collet, MD2, Antonio Colombo, MD3, Harry Suryapranata, MD4, and Giuseppe De Luca, MD, PhD1
Abstract Despite new-generations of drug-eluting stents (DESs), the optimal duration of dual antiplatelet therapy (DAPT) remains controversial. We performed a meta-analysis of randomized trials (RTs) evaluating the effectiveness and safety of shorter versus longer DAPT duration strategies in patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched. The primary end point was mortality. Secondary end points were (1) cardiovascular mortality, (2) nonfatal myocardial infarction, (3) definite/probable stent thrombosis (ST), and (4) major bleedings. We included 11 RTs (n ¼ 32 372 patients). Shorter DAPT duration reduced mortality (odds ratio, OR [95% confidence interval, CI] ¼ 0.85 [0.71-1], P ¼ .05; p heterogeneity ¼ 0.91). Similar results were observed when comparing 3 to 6 versus 12 months DAPT, while a significant increase in recurrent ischemic events was found for 6 to 12 months DAPT versus extended treatment (myocardial infarction: OR [95%CI] ¼ 1.66 [1.37-2], P < .00001; phet ¼ 0.13 and ST: OR [95%CI] ¼ 2.47 [1.72-3.45], P < .00001; phet ¼ 0.12), however, counterbalanced by a significant reduction in major bleeding (OR [95%CI] ¼ 0.60 [0.470.76], P < .0001; phet ¼ 0.38) and a trend in lower mortality. Thus, among selected patients undergoing DES implantation, a shorter DAPT strategy is associated with reduction in mortality and major bleeding but a higher risk of myocardial infarction and ST. A short duration (3-6 months) of DAPT appears as the safest strategy, while a prolonged duration (24-36 months) reduces thrombotic complications but with an excess in major bleeding complications. Keywords dual antiplatelet therapy, duration, drug-eluting stents, meta-analysis
Background Optimal platelet inhibition is a key issue in the treatment of patients undergoing percutaneous coronary interventions (PCIs) and especially in the era of drug-eluting stents (DESs).1 The introduction of new, more potent antiplatelet agents and the identification of patients with high residual platelet reactivity led to better short- and long-term clinical outcomes of patients with coronary artery disease.2-4 Still debated is the ideal duration of dual antiplatelet therapy (DAPT) after coronary stenting, especially after the introduction of second-generation DES, associated with a consistent reduction in stent thrombosis (ST) as compared with first-generation DES.5 A reduced DAPT duration could be considered safe, and also effective, reducing the risk of bleeding complications, which have been demonstrated to impact on mortality.6 On the other hand, very late (>12 months) ST reported after DES implantation suggests that DAPT may be extended beyond the recommended duration of 6 to 12 months.7
Several studies have been conducted so far to define the optimal duration of DAPT after DES implantation. However, they were not powered enough to evaluate hard end points such as mortality and ST and therefore could not provide any conclusive recommendation for the optimal timing of DAPT discontinuation after DES implantation.8 Therefore, the aim of the present meta-analysis was to compare the effectiveness in
1
Division of Cardiology, Azienda Ospedaliera-Universitaria ‘‘Maggiore della Carita`,’’ Eastern Piedmont University, Novara, Italy 2 Institut de Cardiologie, Centre Hospitalier Pitie´-Salpeˆtrie`re (AP-HP, ACTION Group, University Paris 6), Paris, France 3 Interventional Cardiology Unit, San Raffaele Scientific Institute and EMOGVM Centro Cuore Columbus, Milan, Italy 4 Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands Corresponding Author: Giuseppe De Luca, Azienda Ospedaliera-Universitaria ‘‘Maggiore della Carita`,’’ Eastern Piedmont University, Corso Mazzini, 18, Novara 28100, Italy. Email: [email protected]
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
2
Angiology
terms of mortality and bleeding complications of a shorter DAPT strategy versus an extended DAPT strategy in patients undergoing DES implantation.
2209 records idenfied by lierature search
6 addional unpublished records idenfied by manual search
2142 citaons excluded in case of: 1) not full –lenght arcles; 2) no original data; 3) meta-analysis
Methods Eligibility and Search Strategy The literature was scanned by formal searches of electronic databases (MEDLINE, Cochrane, and EMBASE) for clinical studies and furthermore the scientific session abstracts searched on the ‘‘TCT’’ (www.tctmd.com), ‘‘EuroPCR’’ (www.europcr.com), American College of Cardiology (ACC; www.acc.org), American Hospital Association (AHA; www. aha.org), and European Society of Cardiology (ESC; www. escardio.org) Web sites, for oral presentations and/or expert slide presentations from January 1990 to November 2014. The following key words were used: ‘‘dual antiplatelet therapy,’’ ‘‘clopidogrel,’’ ‘‘ticagrelor,’’ ‘‘prasugrel,’’ ‘‘duration,’’ ‘‘drugeluting stent,’’ ‘‘DES,’’ ‘‘randomized.’’ No language restrictions were enforced. Inclusion criteria were (1) patients undergoing PCI with stent implantation, (2) availability of complete clinical data, and (3) randomized treatment allocation. Exclusion criteria were (1) follow-up data in less than 90% of patients and (2) ongoing studies or irretrievable data.
Data Extraction and Validity Assessment Data were independently abstracted by 2 investigators (MV and AS). In case of incomplete or unclear data, the authors were contacted. Disagreements were resolved by consensus. Data were managed according to the intention-to-treat principle. Data on cardiovascular mortality were collected if data on overall mortality were not available.
Outcome Measures Primary end point was overall mortality. Secondary end points were (1) cardiovascular mortality, (2) recurrent myocardial infarction, and (3) ST (definite or probable according to Academic Research Consortium definition). Safety end point was the rate of major bleeding complications (according to protocol definition).
Data Analysis Statistical analysis was performed using the Review Manager 4.27 freeware package, SPSS 17.0 statistical package. Odds ratio (OR) and 95% confidence intervals (95%CI) were used as summary statistics. The pooled OR was calculated using a fixed effect model (Mantel-Haensel). The Breslow-Day test was used to examine the statistical evidence of heterogeneity across the studies (P < .1). Potential publication bias was examined by constructing a ‘‘funnel plot,’’ in which sample size was plotted against ORs (for the primary end point). The study quality was evaluated by the same 2 investigators according to a score, which was expressed on a ordinal scale, allocating 1
73 full-lenght arcles assessed for elegibility
13 randomized trials inially idenfied
60 studies excluded aer inclusion/exclusion criteria applicaon (outcome endpoints, randomized design, treatment compleon >90% of study populaon) 2 trials excluded because were duplicates
11 randomized trials included in final meta-analysis
Figure 1. Flow diagram of the systematic overview process.
point for the presence of each of the following: (1) statement of objectives, (2) explicit inclusion and exclusion criteria, (3) description of intervention, (4) objective means of follow-up, (5) description of adverse events, (6) power analysis, (7) description of statistical methods, (8) multicenter design, (9) discussion of withdrawals, and (10) details on medical therapy. A prespecified analysis was performed according to the type of trial (trials comparing DAPT 12 months; 3.1% [281 of 9270] vs 1.8% [171 of 9357], OR [95%CI] ¼ 1.66 [1.37-2], P < .00001; phet ¼ 0.13), whereas similar results were obtained between the 2 treatment groups in trials on short-term DAPT (3-6 months with 12 months; 1.6% [98 of 5963] vs 1.5% [93 of 5992], OR [95%CI] ¼ 1.06 [0.80-1.42], P ¼ .67, phet ¼ 0.65, P interaction ¼ .01). Stent thrombosis. Data on definite/probable ST were available in 30 582 (94.4%) patients (1 study16 evaluated only definite ST). A total of 188 (0.6%) patients experienced such an event. The risk of ST was significantly doubled with shorter versus longer DAPT duration (0.8% [126 of 15 233] vs 0.4% [62 of 15 349], OR [95%CI] ¼ 2.04 [1.52-2.75], P < .00001; phet ¼ 0.12, Figure 6). The results were mainly driven by a significant benefit in ST from extended (beyond 1 year) DAPT duration (12 to >12 months; 1.1% [101 of 9495] vs 0.4% [41 of 9594], OR [95%CI] ¼ 2.47 [1.72-3.55], P < .00001; phet ¼ 0.12), while no significant difference was observed in trials on short DAPT duration (3-6 vs 12 months; 0.5% [29 of 5963] vs 0.4% [23 of 5992], OR [95%CI] ¼ 1.27 [0.73-2.19], P ¼ .40; phet ¼ 0.59, P interaction ¼ .05). Safety end point. Data on major bleedings were available in 10 studies including 30 400 (92.9%) patients, of whom 339 (1.1%) patients experienced such an event. Thrombolysis in myocardial infarction major definition was used in 7 studies.8,10,12,14,16,17,19 As displayed in Figure 7, shorter DAPT duration significantly reduced the rate of major bleeding events (0.8% [127 of 15 145] vs 1.4% [212 of 15 255], OR [95%CI] ¼ 0.61 [0.49-0.76], P < .00001; phet ¼ 0.86). The reduction in bleeding events was significant in trials evaluating extended DAPT duration (12 vs > 12 months; 1.2% [104 of 9182] vs 1.9% [179 of 9263], OR [95%CI] ¼ 0.60 [0.47-0.76], P < .0001; phet ¼ 0.38), while trials evaluating short DAPT duration showed a consistent and similar trend as indicated by the OR and the interaction value (3-6 vs 12 months; 0.4% [23 of 5963] vs 0.6% [33 of 5992], OR [95%CI] ¼ 0.70 [0.41-1.20], P ¼ .19, phet ¼ 0.99, P interaction ¼ .59).
Discussion The present study represents the largest meta-analysis of RTs comparing the safety and efficacy in terms of ischemic and bleeding complications of different DAPT duration strategies in patients undergoing percutaneous coronary revascularization with DES. Our meta-analysis showed that among patients undergoing DES implantation, a shorter DAPT duration is safer and associated with a significant reduction in overall mortality, a significant reduction in major bleeding, but associated with higher risk of late thrombotic complications, including ST.
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
4
Downloaded from ang.sagepub.com at Bobst Library, New York University on July 24, 2015
RESET
EXCELLENT
Study
2012
2012
Publication
Multicenter, RCT
Multicenter, RCT
Type
ASA þ clopidogrel
ASA þ clopidogrel
Strategy Shorter DAPT
Table 1. Characteristics of Included Randomized Studies.
3
6
Months
ASA þ clopidogrel
ASA þ clopidogrel
Strategy Longer DAPT
Antiplatelet Treatment
12
12
Months
8.
7.
6.
4. 5.
2. 3.
1.
Coronary artery disease including stable angina, unstable angina, and acute myocardial infarction. Age 20 years or older. Typical chest pain and objective evidences of myocardial ischemia on the electrocardiogram or positive functional studies consistent. Signed informed consent. Significant coronary artery stenosis (>50% by visual estimate), which is considered for coronary revascularization with stent implantation. Reference vessel diameter of 2.5 to 4.0 mm by the visual estimation of operator assessment. Lesion success (30% or less residual stenosis by visual assessment over the entire stent length, with thrombolysis in myocardial infarction [TIMI]-3 flow and no more than type B peristent dissection in National Heart, Lung, and Blood Institute [NHLBI] criteria). Lesion and stent length for shortlesion subgroup: (1) length of single stent per single lesion 24 mm and (2) summation of total length of all
1. One lesion in a native coronary vessel with a reference diameter of 2.25 to 4.25 mm. 2. Stenosis of 50% by visual estimation and evidence of myocardial ischemia such as stable angina, unstable angina, recent myocardial infarction, silent ischemia, a positive functional study, or reversible changes in ECG consistent with ischemia. 3. Documentation of ischemia was not mandatory for lesions with 75% stenosis.
Inclusion
12.
10. 11.
7. 8. 9.
6.
5.
4.
3.
2.
13. 1.
11. 12.
10.
9.
8.
6. 7.
5.
4.
3.
1. 2.
10
10
Quality Score
(continued)
Myocardial infarction within 72 h. Severely compromised ventricular dysfunction (ejection fraction
