Coronary Interventions Clinical Impact of Gastrointestinal Bleeding in Patients Undergoing Percutaneous Coronary Interventions Konstantinos C. Koskinas, MD, MSc*; Lorenz Räber, MD, PhD*; Thomas Zanchin, MD; Peter Wenaweser, MD; Stefan Stortecky, MD; Aris Moschovitis, MD; Ahmed A. Khattab, MD; Thomas Pilgrim, MD; Stefan Blöchlinger, MD; Christina Moro, MSc; Peter Jüni, MD; Bernhard Meier, MD; Dik Heg, PhD; Stephan Windecker, MD Background—The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. Methods and Results—Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67–6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99–7.07; P30 days) GIB to allow for comparisons with previous reports, which focused on in-hospital or 30-day GIB after PCI.8,10,13 A clinical event committee adjudicated all events using original source documents. MI was defined according to the modified historical definition.20 Stroke was defined as rapid development of clinical signs of focal or global disturbance of cerebral function lasting >24 hours with imaging evidence of acute, clinically relevant brain lesion.
Statistical Analyses Statistical analyses were performed with STATA version 13.1 (Stata Corp, College Station, TX). Continuous variables are summarized as mean±SD; categorical ones, as actual numbers and percentages. To assess the association between baseline variables and time to the occurrence of GIB, we used univariable hazard ratios and P values derived from Cox proportional hazard models after multiple imputation of missing baseline data (combined estimate of 10 data sets using Rubin rule). Predictors for GIB were assessed singly for inclusion into a Cox regression model of time to the first GIB, using P70%) of overall events and for the vast majority (>80%) of severe bleeding events; (3) independent predictors of 1-year GIB are mostly patient-specific factors, including increasing age, active smoking, and a history of GIB or malignancy; (4) triple antithrombotic therapy, but
not the use of DAPT, prasugrel, OAC, or periprocedural antithrombotic medications, is the single drug-related predictor of GIB; (5) upper GIB events are twice as frequent, and display a more delayed time course, compared with lower GIB; and (6) GIB is an independent predictor of 1-year mortality. The present cohort advances our understanding about the role of GIB after PCI in several important ways. Earlier relevant studies included low rates of DES (ranging from none9,10,15 to 6%12 to about a third of patients in the Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY] analysis11) and as a result consistently used regimens of shorter DAPT duration, or they focused specifically on patient subsets with potentially confounding characteristics (eg, ACS10,11 or severe heart failure9). In contrast, we assessed patients as encountered in routine clinical practice across the entire spectrum of coronary artery disease, including individuals with noncardiac comorbidities (eg, malignancy) or indication for OAC, who were excluded from previous randomized clinical trials assessing GIB.11,15 In addition, we addressed the correlates and impact of GIB occurring late (up to 1 year) after the procedure, and we analyzed patients who received treatment according to current practice standards, including implantation of predominantly DES, prolonged DAPT duration, and novel P2Y12 inhibitors. A notable limitation of this analysis is the small number of events in patients with GIB, such that
Table 3. Medications Used During Index Intervention and at Discharge Patients Developed GIB Yes (n=65)
No (n=6147)
Crude HR (95% CI)
P Value
62/65 (95.4)
5965/6135 (97.2)
0.60 (0.19–1.92)
0.39
Glycoportein IIb/IIIa inhibitors
6/65 (9.2)
472/6134 (7.7)
1.23 (0.53–2.85)
0.60
Abciximab
6/65 (9.2)
462/6134 (7.5)
1.25 (0.54–2.90)
0.60
4/65 (6.2)
769/6147 (12.5)
1.0 (reference)
…
Variable During PCI, n (%) Unfractionated heparin
Loading dose within 24 h of PCI None Clopidogrel
49/65 (75.4)
4150/6147 (67.5)
2.22 (0.80–6.16)
0.12
Prasugrel
5/65 (7.7)
494/6147 (8.0)
1.98 (0.53–7.37)
0.31
Ticagrelor
1/65 (1.5)
105/6147 (1.7)
1.73 (0.19–15.45)
0.62
Clopidogrel and prasugrel
4/65 (6.2)
578/6147 (9.4)
1.30 (0.32–5.18)
0.71
Acetylsalicylic acid
63/64 (98.4)
5910/6008 (98.4)
0.83 (0.12–6.01)
0.86
Clopidogrel
51/64 (79.7)
4504/6007 (75.0)
1.34 (0.69–2.60)
0.38
Prasugrel
11/64 (17.2)
1171/6007 (19.5)
0.80 (0.39–1.62)
0.53
At discharge, n (%)*
Ticagrelor
4/64 (6.3)
176/6090 (2.9)
2.52 (0.91–6.96)
0.08
Any dual antiplatelet therapy
63/64 (98.4)
5759/6008 (95.9)
2.27 (0.31–16.39)
0.42
Oral anticoagulation
10/64 (15.6)
496/6006 (8.1)
2.52 (1.27–4.99)
0.01
Triple antithrombotic therapy
10/64 (15.6)
403/6006 (6.7)
3.08 (1.55–6.10)
30 days) events accounted for the majority of all GIB events throughout 1 year and for the great majority of severe GIB. These findings emphasize the need for prolonged surveillance of patients at risk of GIB after PCI by current standards. It also shows that the majority of GIB is disconnected from the index procedure and is more importantly influenced by underlying patient-related factors. GIB events were predicted mainly by patient-specific characteristics rather than medication-related factors. In line with earlier reports, we found that increasing age, a history of
previous GIB and malignancy, and active smoking—the only modifiable feature—persist as decisive risk factors of GIB in patients treated by contemporary practice. Triple antithrombotic therapy with OAC plus DAPT at discharge—at a rate that notably remained unchanged until the actual occurrence of bleeding—was the single drug-related factor that independently predicted GIB. This finding complements observations of previous studies, in which OAC use was contraindicated10 or not reported. Triple therapy has repeatedly been associated with an excess of major bleeding in previous large-scale registries.25,26 Our observation of an increased risk of GIB underlines the importance of carefully assessing the risk:benefit ratio of this regimen according to the risk for thromboembolism (ie, CHA2DS2-VASc score) and bleeding hazard (HASBLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol] score).27 The increased risk of non-CABG–related (mainly GIBdriven) bleedings in patients receiving prasugrel16 or ticagrelor17 compared with clopidogrel in randomized trials was not confirmed in multivariable analysis in the present cohort, despite the fact that novel P2Y12 inhibitors were administered to >1200 ACS patients with a concurrent loading dose of clopidogrel in >50% of those patients. This may be related to the careful evaluation of relative contraindications to potent P2Y12 inhibitors and the preferential use of prasugrel, in particular, among patients with STEMI in the present cohort. Along this line, no bleeding excess was attributed to prasugrel in The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS), where contraindications for prasugrel were also applied.28 Of note, we used prasugrel primarily in patients with STEMI, a subgroup of patients with no increase of bleeding complications in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial.29 Periprocedural medications were not related to 30-day, or overall 1-year GIB. Notably, because virtually all patients
Figure 3. Use of dual antiplatelet therapy (DAPT; A), triple antithrombotic therapy (B), and proton pump inhibitors (C) at discharge, immediately preceding and after the gastrointestinal bleeding (GIB) event, and at 1 year. For patients without GIB, rates of medication use are shown at discharge and at 1 year. Difference between groups are compared at 1-year follow-up. n/a indicates not applicable.
7 Koskinas et al Gastrointestinal Bleeding After PCI
Figure 4. Multivariable predictors of 1-year gastrointestinal bleeding (GIB). CI indicates confidence interval; and HR, hazard ratio.
received heparin, our results cannot be directly extrapolated to patients receiving bivalirudin, which has been consistently linked to reduced bleeding complications compared with heparin-based regimens.30 In a landmark analysis of the ACUITY trial, periprocedural administration of GP IIb/IIIa inhibitors was more frequent in patients who experienced GIB within 30 days after an ACS, and heparin plus a GP IIb/IIIa inhibitor showed a trend toward higher risk of GIB in multivariable analysis.10 In the present registry, a role of GP IIb/IIIa was not confirmed for the development of GIB complications. One can speculate on possible reasons underlying these discordant findings. In ACUITY, half of the patients who received a GP IIb/IIIa inhibitor were allocated to upstream administration with a median of 4 hours duration of pre-angiography, and an 18 hours total duration of GP IIb/IIIa inhibitor administration. Of note, both upstream initiation and prolonged use of GP IIb/IIIa inhibitors have been closely linked to increased bleeding risk.31 In contrast, in this cohort GP IIb/ IIIa inhibitors were limited to patients undergoing primary PCI as bailout strategy without prolonged administration. In patients with GIB, the use of DAPT was less frequent at 1 year, despite similarly high rates of DES implantation at
the time of the index procedure. Importantly, DAPT was discontinued in almost half of the patients with GIB immediately after the bleeding event, that is, at a mean of 4 months after the intervention. Although the timing of DAPT discontinuation was not consistently available for patients without GIB, it is conceivable that the earlier discontinuation of DAPT in patients who developed GIB might have contributed to the higher incidence of ischemic cardiac and cerebrovascular events; this cannot be further substantiated, however, owing to the nonrandomized nature of this study. The feasibility of detecting either upper32 or lower GIB33 in the acute setting of ACS has been previously demonstrated, yet the relative incidence, time course, and clinical correlates of upper versus lower GIB after PCI have only undergone minimal investigation. The increased rate of upper versus lower GIB in our study is in agreement with findings from unselected, general populations.18 Upper GIB events predominated and occurred later compared with lower GIB. This observations lends further support to prolonged PPI administration in patients deemed susceptible to GIB after PCI as emphasized by current recommendations.23 The relatively low proportion (48%) of patients with subsequent GIB who received PPI at discharge, and the substantial drop to only 28% before the GIB event is in line with previous evidence of suboptimal gastrointestinal prophylaxis in patients receiving DAPT.34 Although this finding does not directly indicate a causal relationship, it is consistent with evidence from randomized trials demonstrating reduced gastrointestinal complications in patients on DAPT who received omeprazole,35 and emphasizes the need for closer attention to clinical and medication-related risk predictors of GIB.
Limitations This study has several limitations owing to its observational, nonrandomized design. First, the registry was not specifically designed to evaluate predictors and clinical outcomes of GIB; however, bleeding outcomes were prospectively defined outcome measures and were specifically evaluated during 1 year follow-up. Second, the single-center nature of the study may limit the external validity of our findings. Third, the association between GIB and clinical outcomes may be confounded by variables that were not recorded (eg, subclinical malignancies). Fourth, atrial fibrillation was not recorded for the purpose of this analysis. However, we previously found a 5.3% prevalence of atrial fibrillation in consecutive patients treated with PCI at our institution36; hence, atrial fibrillation most probably represented the main indication for triple antithrombotic therapy in this study population. Finally, in this sizable cohort of patients receiving contemporary treatment the rate of GIB and the number of events in patients who experienced GIB were low; this probably reflects favorable outcomes for patients treated by current standards, but it may also limit the power of the study and the precision of the analysis of GIB-related risk.
Conclusions Figure 5. Multivariable predictors of all-cause mortality (A) and the composite of death, myocardial infarction (MI) or stroke during 1 year (B). CI indicates confidence interval; DES, drug-eluting stent; HR, hazard ratio; and STEMI, ST-segment–elevation myocardial infarction.
In this contemporary population of consecutively enrolled patients undergoing PCI, GIB was the most common bleeding complication within 1 year. GIB is predicted mainly by patient-specific rather than drug-related factors, it affects
8 Koskinas et al Gastrointestinal Bleeding After PCI predominantly the upper gastrointestinal tract—hence, it may largely be amenable to prophylactic use of gastric protection therapies23––and appears to have a profound effect on 1-year mortality. These findings indicate the need for thorough assessment of the risk of GIB after PCI, and for prolonged vigilance and implementation of bleeding avoidance strategies (eg, cautious administration of triple antithrombotic therapy) in patients with high-risk characteristics.
Disclosures None.
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Supplemental Material Supplemental Table. Clinical outcomes within one year of follow-up in patients with vs. without GIB. Number of events GIB
No GIB
n=65
n=6147
GIB vs. no GIB* before/after GIB*
Variable HR (95% CI)
P value
n=65
Death
9 (14.0)
377 (6.4)
6.31 (3.12–12.78)
0.0000
0/9
Myocardial infarction
1 (1.9)
215 (3.7)
1.47 (0.21–10.36)
0.6985
0/1
Revascularization (any)
6 (10.4)
450 (8.0)
2.00 (0.83–4.83)
0.1224
1/5
Death or MI
10 (15.6)
566 (9.6)
4.93 (2.54-9.59)
0.0000
0/10
Death, MI or stroke
13 (20.2)
596 (10.1)
5.38 (2.85-10.15)
0.0000
2/11
Cardiac death, MI or stroke
9 (14.2)
526 (8.9)
4.20 (1.93-9.14)
0.0003
2/7
GIB indicates gastrointestinal bleeding; MI, myocardial infarction. *: Hazard ratios (95% confidence intervals) with robust standard errors comparing after GIB vs. before GIB or no GIB, by splitting patient records at the date of GIB (assuming events on the date of GIB are attributed to GIB).
1
Supplemental Figure. Schematic presentation of study flow.
2
Clinical Impact of Gastrointestinal Bleeding in Patients Undergoing Percutaneous Coronary Interventions Konstantinos C. Koskinas, Lorenz Räber, Thomas Zanchin, Peter Wenaweser, Stefan Stortecky, Aris Moschovitis, Ahmed A. Khattab, Thomas Pilgrim, Stefan Blöchlinger, Christina Moro, Peter Jüni, Bernhard Meier, Dik Heg and Stephan Windecker Circ Cardiovasc Interv. 2015;8: doi: 10.1161/CIRCINTERVENTIONS.114.002053 Circulation: Cardiovascular Interventions is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-7640. Online ISSN: 1941-7632
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Statistical Analyses Statistical analyses were performed with STATA version 13.1 (Stata Corp, College Station, TX). Continuous variables are summarized as mean±SD; categorical ones, as actual numbers and percentages. To assess the association between baseline variables and time to the occurrence of GIB, we used univariable hazard ratios and P values derived from Cox proportional hazard models after multiple imputation of missing baseline data (combined estimate of 10 data sets using Rubin rule). Predictors for GIB were assessed singly for inclusion into a Cox regression model of time to the first GIB, using P70%) of overall events and for the vast majority (>80%) of severe bleeding events; (3) independent predictors of 1-year GIB are mostly patient-specific factors, including increasing age, active smoking, and a history of GIB or malignancy; (4) triple antithrombotic therapy, but
not the use of DAPT, prasugrel, OAC, or periprocedural antithrombotic medications, is the single drug-related predictor of GIB; (5) upper GIB events are twice as frequent, and display a more delayed time course, compared with lower GIB; and (6) GIB is an independent predictor of 1-year mortality. The present cohort advances our understanding about the role of GIB after PCI in several important ways. Earlier relevant studies included low rates of DES (ranging from none9,10,15 to 6%12 to about a third of patients in the Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY] analysis11) and as a result consistently used regimens of shorter DAPT duration, or they focused specifically on patient subsets with potentially confounding characteristics (eg, ACS10,11 or severe heart failure9). In contrast, we assessed patients as encountered in routine clinical practice across the entire spectrum of coronary artery disease, including individuals with noncardiac comorbidities (eg, malignancy) or indication for OAC, who were excluded from previous randomized clinical trials assessing GIB.11,15 In addition, we addressed the correlates and impact of GIB occurring late (up to 1 year) after the procedure, and we analyzed patients who received treatment according to current practice standards, including implantation of predominantly DES, prolonged DAPT duration, and novel P2Y12 inhibitors. A notable limitation of this analysis is the small number of events in patients with GIB, such that
Table 3. Medications Used During Index Intervention and at Discharge Patients Developed GIB Yes (n=65)
No (n=6147)
Crude HR (95% CI)
P Value
62/65 (95.4)
5965/6135 (97.2)
0.60 (0.19–1.92)
0.39
Glycoportein IIb/IIIa inhibitors
6/65 (9.2)
472/6134 (7.7)
1.23 (0.53–2.85)
0.60
Abciximab
6/65 (9.2)
462/6134 (7.5)
1.25 (0.54–2.90)
0.60
4/65 (6.2)
769/6147 (12.5)
1.0 (reference)
…
Variable During PCI, n (%) Unfractionated heparin
Loading dose within 24 h of PCI None Clopidogrel
49/65 (75.4)
4150/6147 (67.5)
2.22 (0.80–6.16)
0.12
Prasugrel
5/65 (7.7)
494/6147 (8.0)
1.98 (0.53–7.37)
0.31
Ticagrelor
1/65 (1.5)
105/6147 (1.7)
1.73 (0.19–15.45)
0.62
Clopidogrel and prasugrel
4/65 (6.2)
578/6147 (9.4)
1.30 (0.32–5.18)
0.71
Acetylsalicylic acid
63/64 (98.4)
5910/6008 (98.4)
0.83 (0.12–6.01)
0.86
Clopidogrel
51/64 (79.7)
4504/6007 (75.0)
1.34 (0.69–2.60)
0.38
Prasugrel
11/64 (17.2)
1171/6007 (19.5)
0.80 (0.39–1.62)
0.53
At discharge, n (%)*
Ticagrelor
4/64 (6.3)
176/6090 (2.9)
2.52 (0.91–6.96)
0.08
Any dual antiplatelet therapy
63/64 (98.4)
5759/6008 (95.9)
2.27 (0.31–16.39)
0.42
Oral anticoagulation
10/64 (15.6)
496/6006 (8.1)
2.52 (1.27–4.99)
0.01
Triple antithrombotic therapy
10/64 (15.6)
403/6006 (6.7)
3.08 (1.55–6.10)
30 days) events accounted for the majority of all GIB events throughout 1 year and for the great majority of severe GIB. These findings emphasize the need for prolonged surveillance of patients at risk of GIB after PCI by current standards. It also shows that the majority of GIB is disconnected from the index procedure and is more importantly influenced by underlying patient-related factors. GIB events were predicted mainly by patient-specific characteristics rather than medication-related factors. In line with earlier reports, we found that increasing age, a history of
previous GIB and malignancy, and active smoking—the only modifiable feature—persist as decisive risk factors of GIB in patients treated by contemporary practice. Triple antithrombotic therapy with OAC plus DAPT at discharge—at a rate that notably remained unchanged until the actual occurrence of bleeding—was the single drug-related factor that independently predicted GIB. This finding complements observations of previous studies, in which OAC use was contraindicated10 or not reported. Triple therapy has repeatedly been associated with an excess of major bleeding in previous large-scale registries.25,26 Our observation of an increased risk of GIB underlines the importance of carefully assessing the risk:benefit ratio of this regimen according to the risk for thromboembolism (ie, CHA2DS2-VASc score) and bleeding hazard (HASBLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol] score).27 The increased risk of non-CABG–related (mainly GIBdriven) bleedings in patients receiving prasugrel16 or ticagrelor17 compared with clopidogrel in randomized trials was not confirmed in multivariable analysis in the present cohort, despite the fact that novel P2Y12 inhibitors were administered to >1200 ACS patients with a concurrent loading dose of clopidogrel in >50% of those patients. This may be related to the careful evaluation of relative contraindications to potent P2Y12 inhibitors and the preferential use of prasugrel, in particular, among patients with STEMI in the present cohort. Along this line, no bleeding excess was attributed to prasugrel in The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS), where contraindications for prasugrel were also applied.28 Of note, we used prasugrel primarily in patients with STEMI, a subgroup of patients with no increase of bleeding complications in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 trial.29 Periprocedural medications were not related to 30-day, or overall 1-year GIB. Notably, because virtually all patients
Figure 3. Use of dual antiplatelet therapy (DAPT; A), triple antithrombotic therapy (B), and proton pump inhibitors (C) at discharge, immediately preceding and after the gastrointestinal bleeding (GIB) event, and at 1 year. For patients without GIB, rates of medication use are shown at discharge and at 1 year. Difference between groups are compared at 1-year follow-up. n/a indicates not applicable.
7 Koskinas et al Gastrointestinal Bleeding After PCI
Figure 4. Multivariable predictors of 1-year gastrointestinal bleeding (GIB). CI indicates confidence interval; and HR, hazard ratio.
received heparin, our results cannot be directly extrapolated to patients receiving bivalirudin, which has been consistently linked to reduced bleeding complications compared with heparin-based regimens.30 In a landmark analysis of the ACUITY trial, periprocedural administration of GP IIb/IIIa inhibitors was more frequent in patients who experienced GIB within 30 days after an ACS, and heparin plus a GP IIb/IIIa inhibitor showed a trend toward higher risk of GIB in multivariable analysis.10 In the present registry, a role of GP IIb/IIIa was not confirmed for the development of GIB complications. One can speculate on possible reasons underlying these discordant findings. In ACUITY, half of the patients who received a GP IIb/IIIa inhibitor were allocated to upstream administration with a median of 4 hours duration of pre-angiography, and an 18 hours total duration of GP IIb/IIIa inhibitor administration. Of note, both upstream initiation and prolonged use of GP IIb/IIIa inhibitors have been closely linked to increased bleeding risk.31 In contrast, in this cohort GP IIb/ IIIa inhibitors were limited to patients undergoing primary PCI as bailout strategy without prolonged administration. In patients with GIB, the use of DAPT was less frequent at 1 year, despite similarly high rates of DES implantation at
the time of the index procedure. Importantly, DAPT was discontinued in almost half of the patients with GIB immediately after the bleeding event, that is, at a mean of 4 months after the intervention. Although the timing of DAPT discontinuation was not consistently available for patients without GIB, it is conceivable that the earlier discontinuation of DAPT in patients who developed GIB might have contributed to the higher incidence of ischemic cardiac and cerebrovascular events; this cannot be further substantiated, however, owing to the nonrandomized nature of this study. The feasibility of detecting either upper32 or lower GIB33 in the acute setting of ACS has been previously demonstrated, yet the relative incidence, time course, and clinical correlates of upper versus lower GIB after PCI have only undergone minimal investigation. The increased rate of upper versus lower GIB in our study is in agreement with findings from unselected, general populations.18 Upper GIB events predominated and occurred later compared with lower GIB. This observations lends further support to prolonged PPI administration in patients deemed susceptible to GIB after PCI as emphasized by current recommendations.23 The relatively low proportion (48%) of patients with subsequent GIB who received PPI at discharge, and the substantial drop to only 28% before the GIB event is in line with previous evidence of suboptimal gastrointestinal prophylaxis in patients receiving DAPT.34 Although this finding does not directly indicate a causal relationship, it is consistent with evidence from randomized trials demonstrating reduced gastrointestinal complications in patients on DAPT who received omeprazole,35 and emphasizes the need for closer attention to clinical and medication-related risk predictors of GIB.
Limitations This study has several limitations owing to its observational, nonrandomized design. First, the registry was not specifically designed to evaluate predictors and clinical outcomes of GIB; however, bleeding outcomes were prospectively defined outcome measures and were specifically evaluated during 1 year follow-up. Second, the single-center nature of the study may limit the external validity of our findings. Third, the association between GIB and clinical outcomes may be confounded by variables that were not recorded (eg, subclinical malignancies). Fourth, atrial fibrillation was not recorded for the purpose of this analysis. However, we previously found a 5.3% prevalence of atrial fibrillation in consecutive patients treated with PCI at our institution36; hence, atrial fibrillation most probably represented the main indication for triple antithrombotic therapy in this study population. Finally, in this sizable cohort of patients receiving contemporary treatment the rate of GIB and the number of events in patients who experienced GIB were low; this probably reflects favorable outcomes for patients treated by current standards, but it may also limit the power of the study and the precision of the analysis of GIB-related risk.
Conclusions Figure 5. Multivariable predictors of all-cause mortality (A) and the composite of death, myocardial infarction (MI) or stroke during 1 year (B). CI indicates confidence interval; DES, drug-eluting stent; HR, hazard ratio; and STEMI, ST-segment–elevation myocardial infarction.
In this contemporary population of consecutively enrolled patients undergoing PCI, GIB was the most common bleeding complication within 1 year. GIB is predicted mainly by patient-specific rather than drug-related factors, it affects
8 Koskinas et al Gastrointestinal Bleeding After PCI predominantly the upper gastrointestinal tract—hence, it may largely be amenable to prophylactic use of gastric protection therapies23––and appears to have a profound effect on 1-year mortality. These findings indicate the need for thorough assessment of the risk of GIB after PCI, and for prolonged vigilance and implementation of bleeding avoidance strategies (eg, cautious administration of triple antithrombotic therapy) in patients with high-risk characteristics.
Disclosures None.
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Supplemental Material Supplemental Table. Clinical outcomes within one year of follow-up in patients with vs. without GIB. Number of events GIB
No GIB
n=65
n=6147
GIB vs. no GIB* before/after GIB*
Variable HR (95% CI)
P value
n=65
Death
9 (14.0)
377 (6.4)
6.31 (3.12–12.78)
0.0000
0/9
Myocardial infarction
1 (1.9)
215 (3.7)
1.47 (0.21–10.36)
0.6985
0/1
Revascularization (any)
6 (10.4)
450 (8.0)
2.00 (0.83–4.83)
0.1224
1/5
Death or MI
10 (15.6)
566 (9.6)
4.93 (2.54-9.59)
0.0000
0/10
Death, MI or stroke
13 (20.2)
596 (10.1)
5.38 (2.85-10.15)
0.0000
2/11
Cardiac death, MI or stroke
9 (14.2)
526 (8.9)
4.20 (1.93-9.14)
0.0003
2/7
GIB indicates gastrointestinal bleeding; MI, myocardial infarction. *: Hazard ratios (95% confidence intervals) with robust standard errors comparing after GIB vs. before GIB or no GIB, by splitting patient records at the date of GIB (assuming events on the date of GIB are attributed to GIB).
1
Supplemental Figure. Schematic presentation of study flow.
2
Clinical Impact of Gastrointestinal Bleeding in Patients Undergoing Percutaneous Coronary Interventions Konstantinos C. Koskinas, Lorenz Räber, Thomas Zanchin, Peter Wenaweser, Stefan Stortecky, Aris Moschovitis, Ahmed A. Khattab, Thomas Pilgrim, Stefan Blöchlinger, Christina Moro, Peter Jüni, Bernhard Meier, Dik Heg and Stephan Windecker Circ Cardiovasc Interv. 2015;8: doi: 10.1161/CIRCINTERVENTIONS.114.002053 Circulation: Cardiovascular Interventions is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-7640. Online ISSN: 1941-7632
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circinterventions.ahajournals.org/content/8/5/e002053
Data Supplement (unedited) at: http://circinterventions.ahajournals.org/content/suppl/2015/04/28/CIRCINTERVENTIONS.114.002053.DC1.html
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