Incidence, Correlates, and Clinical Impact of Nuisance Bleeding
Background Nuisance bleeding (NB) after dual antiplatelet therapy (DAPT) is not well characterized despite its potential to impact patient compliance. We therefore aimed to evaluate the incidence, correlates, and clinical impact of NB after DAPT after drug-eluting stent (DES) implantation.
Methods Included were 2,948 patients with DES implantation who were discharged on DAPT for 12 months. New bleeding classifications were used: alarming bleeding, internal bleeding, and NB.
Results After excluding patients with alarming bleeding (9 [0.3%]) and internal bleeding (128 [4.3%]), the 2,811 remaining patients were divided into 2 groups: those with NB (812 [28.9%]) and those without (1,999 [71.1%]). Patients with NB were significantly younger (63.0 ± 11.4 vs 65.2 ± 11.6 years, P < .001), were more often white (82.0% vs 69.6%, P < .001), had lower body mass indices (29.2 ± 6.1 vs 29.8 ± 6.0 kg/m, P = .01), and a lower prevalence of diabetes (25.5% vs 34.8%, P < .001) compared to those without NB. At 1 year, the rate of major adverse cardiac events was higher in the NB group compared to the nonbleeding group (77 [9.4%] vs 134 [6.7%], P = .02). In the NB group, 46 patients (5.7%) stopped 1 or both antiplatelet therapies. Thirty-five (4.3%) discontinued clopidogrel, 16 (2.0%) stopped aspirin, and 5 (0.61%) stopped both as a result of the reported NB. Multivariable analysis detected younger age, lower body mass index, white race, and without diabetes as correlates associated with NB while on clopidogrel therapy.
Conclusion Nuisance bleeding is common in patients on prolonged DAPT post-DES implantation and can impact compliance. Nuisance bleeding appears to have important clinical implications and, if confirmed in prospective trials, should be added to the safety end points assessing new antiplatelet agents.
Prolonged dual antiplatelet treatment (DAPT) with aspirin and clopidogrel significantly reduces the risk of major coronary events and fatal or nonfatal myocardial infarction (MI) compared to aspirin alone. Current recommendations call for a minimum of 12 months of DAPT post–drug-eluting stent (DES) implantation for the prevention of stent thrombosis. However, as shown in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial, prolonged DAPT carries with it a bleeding risk. For patients with symptomatic atherothrombosis, DAPT was associated with higher severe bleeding rates compared to treatment with aspirin alone. The degree of platelet inhibition after clopidogrel treatment varies among patients in a normal bell-shaped distribution. Although most of the recent studies focused on resistance and hyporesponsiveness to clopidogrel, patients may have clopidogrel hyperresponsiveness, which can result in an increased bleeding rate. Most of the trials evaluating prolonged administration of clopidogrel or prasugrel, such as Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel Maintaining Dosage in Acute Coronary Syndrome After Drug Eluting Stent Implantation (CREDO), CHARISMA, and TRITON-TIMI 38, reported major bleeding as defined by Thrombolysis In Myocardial Infarction (TIMI) (major bleeding rates of 1.8%-3.7% and minor 1.7%-5.1%) and Global Use of Strategies to Open Coronary Arteries (GUSTO) bleeding criteria (severe bleeding 1.7%-2.2% and moderate 1.2%-2.1%). Mild bleeding rates were not reported. Superficial or nuisance bleeding (NB) after DAPT does not fit into these traditional classifications. New bleeding classifications have been proposed to better cover the entire spectrum of bleeding complications, including minor or superficial (ie, nuisance) bleeding—alarming bleeding, internal bleeding, and NB. These new classifications are more suitable for recent advances in percutaneous interventional techniques and paired with modern pharmacotherapy have substantially changed the clinical presentation of bleeding events. Easy bruising was observed in 48% of patients with stable coronary artery disease treated with clopidogrel and aspirin. We previously reported that up to one third of patients postpercutaneous coronary intervention (PCI) with DES treated with DAPT had NB. The current study aims to detect correlates for NB and the impact NB has on clinical events.
Abstract and Introduction
Abstract
Background Nuisance bleeding (NB) after dual antiplatelet therapy (DAPT) is not well characterized despite its potential to impact patient compliance. We therefore aimed to evaluate the incidence, correlates, and clinical impact of NB after DAPT after drug-eluting stent (DES) implantation.
Methods Included were 2,948 patients with DES implantation who were discharged on DAPT for 12 months. New bleeding classifications were used: alarming bleeding, internal bleeding, and NB.
Results After excluding patients with alarming bleeding (9 [0.3%]) and internal bleeding (128 [4.3%]), the 2,811 remaining patients were divided into 2 groups: those with NB (812 [28.9%]) and those without (1,999 [71.1%]). Patients with NB were significantly younger (63.0 ± 11.4 vs 65.2 ± 11.6 years, P < .001), were more often white (82.0% vs 69.6%, P < .001), had lower body mass indices (29.2 ± 6.1 vs 29.8 ± 6.0 kg/m, P = .01), and a lower prevalence of diabetes (25.5% vs 34.8%, P < .001) compared to those without NB. At 1 year, the rate of major adverse cardiac events was higher in the NB group compared to the nonbleeding group (77 [9.4%] vs 134 [6.7%], P = .02). In the NB group, 46 patients (5.7%) stopped 1 or both antiplatelet therapies. Thirty-five (4.3%) discontinued clopidogrel, 16 (2.0%) stopped aspirin, and 5 (0.61%) stopped both as a result of the reported NB. Multivariable analysis detected younger age, lower body mass index, white race, and without diabetes as correlates associated with NB while on clopidogrel therapy.
Conclusion Nuisance bleeding is common in patients on prolonged DAPT post-DES implantation and can impact compliance. Nuisance bleeding appears to have important clinical implications and, if confirmed in prospective trials, should be added to the safety end points assessing new antiplatelet agents.
Introduction
Prolonged dual antiplatelet treatment (DAPT) with aspirin and clopidogrel significantly reduces the risk of major coronary events and fatal or nonfatal myocardial infarction (MI) compared to aspirin alone. Current recommendations call for a minimum of 12 months of DAPT post–drug-eluting stent (DES) implantation for the prevention of stent thrombosis. However, as shown in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial, prolonged DAPT carries with it a bleeding risk. For patients with symptomatic atherothrombosis, DAPT was associated with higher severe bleeding rates compared to treatment with aspirin alone. The degree of platelet inhibition after clopidogrel treatment varies among patients in a normal bell-shaped distribution. Although most of the recent studies focused on resistance and hyporesponsiveness to clopidogrel, patients may have clopidogrel hyperresponsiveness, which can result in an increased bleeding rate. Most of the trials evaluating prolonged administration of clopidogrel or prasugrel, such as Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel Maintaining Dosage in Acute Coronary Syndrome After Drug Eluting Stent Implantation (CREDO), CHARISMA, and TRITON-TIMI 38, reported major bleeding as defined by Thrombolysis In Myocardial Infarction (TIMI) (major bleeding rates of 1.8%-3.7% and minor 1.7%-5.1%) and Global Use of Strategies to Open Coronary Arteries (GUSTO) bleeding criteria (severe bleeding 1.7%-2.2% and moderate 1.2%-2.1%). Mild bleeding rates were not reported. Superficial or nuisance bleeding (NB) after DAPT does not fit into these traditional classifications. New bleeding classifications have been proposed to better cover the entire spectrum of bleeding complications, including minor or superficial (ie, nuisance) bleeding—alarming bleeding, internal bleeding, and NB. These new classifications are more suitable for recent advances in percutaneous interventional techniques and paired with modern pharmacotherapy have substantially changed the clinical presentation of bleeding events. Easy bruising was observed in 48% of patients with stable coronary artery disease treated with clopidogrel and aspirin. We previously reported that up to one third of patients postpercutaneous coronary intervention (PCI) with DES treated with DAPT had NB. The current study aims to detect correlates for NB and the impact NB has on clinical events.
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