Nuisance bleeding with prolonged dual antiplatelet therapy after acute myocardial infarction and its impact on health status

Abstract

Objectives: The purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL.

Background: Prolonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge "nuisance" bleeding with DAPT and its impact on quality of life (QOL) are unknown.

Methods: Data from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with "nuisance" bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined.

Results: Nuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (-2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52).

Conclusions: Nuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding.

Figure 1. Independent association of self-reported nuisance bleeding with DAPT at discharge or 1 month, 6 months or 1 year

This is a multivariable, repeated-measures, modified Poisson regression model with robust variance estimation. Nuisance bleeding at 1, 6, and 12 months is the dependent variable (repeated measures), and the independent variables were those considered to be predictors of bleeding, including DES use, DAPT at discharge, 1 month, 6 months, or 12 months (main exposure variable), age, female gender, insurance status, GRACE 6-month mortality risk score, CRUSADE bleeding risk score, history of atrial fibrillation at baseline, occurrence of in-hospital bleeding, baseline hemoglobin and baseline creatinine, development of atrial fibrillation or warfarin use during hospitalization, or coronary artery bypass graft (CABG) surgery in-hospital and all significant interactions of above covariates with the three time-points. Variables other than CRUSADE and GRACE risk scores not shown. Other statistically significant variables associated independently with nuisance bleeding were female gender (RR 1.29, 95% CI 1.19 to 1.40, P-value <0.0001) and history of atrial fibrillation (RR 1.35, 95% CI 1.15 to 1.57, P-value = 0.0002) [Data not shown in the figure]. X-axis graphs the rate ratio (RR). Numbers alongside the floating bars denote the corresponding rate ratios and 95% CI.

Figure 2. Independent association of nuisance bleeding with quality of life (EQ5D VAS)

Estimates (with 95% CI) indicate absolute points on the EQ5D VAS score. Negative sign indicates a decrement in QOL. This is a multivariable, hierarchical linear regression model with EQ5D VAS score at 1 month as the dependent variable and nuisance bleeding at 1 month as the predictor variable of interest. The model adjusts for other confounding variables including age, female gender, insurance status, GRACE 6-month mortality risk score, CRUSADE bleeding risk score, history of atrial fibrillation at baseline, baseline hemoglobin and baseline creatinine, development of atrial fibrillation or warfarin use during hospitalization, or coronary artery bypass graft (CABG) surgery in-hospital. X-axis graphs the change in QOL scores assessed via the EQ5D VAS. Numbers alongside the floating bars denote the corresponding estimate with its 95% CI.

Figure 3. Association of nuisance bleeding with re-hospitalization

Panel A: Kaplan-Meier survival estimates of rehospitalization-free event rate X-axis represents time in months. Y-axis represents the probability of being rehospitalization-free. P-value is for the log-rank test. Panel B: Cox multivariable regression model. X-axis graphs the hazard ratio and the floating bars denote the corresponding estimate with its 95% CI.

Figure 3. Association of nuisance bleeding with re-hospitalization

Panel A: Kaplan-Meier survival estimates of rehospitalization-free event rate X-axis represents time in months. Y-axis represents the probability of being rehospitalization-free. P-value is for the log-rank test. Panel B: Cox multivariable regression model. X-axis graphs the hazard ratio and the floating bars denote the corresponding estimate with its 95% CI.