Impact of blood transfusion on in-hospital myocardial infarctions according to patterns of acute coronary syndrome: Insights from the BleeMACS registry

doi:10.1016/j.ijcard.2016.07.075

International Journal of Cardiology

Volume 221, 15 October 2016, Pages 364-370

https://doi.org/10.1016/j.ijcard.2016.07.075 Get rights and content

Abstract

Background

Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS).

Methods

Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS).

Results

Overall, 13,975 patients were included: mean age was 64.1 years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244–7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients.

Conclusions

In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis.

Introduction

Anemia negatively affects the prognosis of patients hospitalized for acute coronary syndromes (ACS), increasing the mortality and incidence of adverse cardiovascular (CV) events, especially in patients with complex coronary disease [1], [2]. Blood transfusions (BTs) can rapidly and effectively restore hemoglobin (Hb) and hematocrit levels, but safety and effectiveness of this practice have been increasingly doubted. Several studies reported a substantial negative effect on short and long-term outcome [3], [4]. Despite these evidences, BTs are still widely administered in the ACS setting, with many challenges related to dual antiplatelet therapy [5], [6], [7].

Moreover, little is known about the mechanisms by which BTs could lead to adverse outcomes. Incomplete correction for confounding factors plays a significant role, as patients receiving BTs are usually more frail and present a higher comorbidity burden. A direct cause–effect relationship between BTs and CV events, however, possibly involving recurrence of acute myocardial infarction (re-AMI), has been described [8].

Furthermore, scarce data detail if different clinical presentations of ACS (ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS, which include myocardial infarction (NSTEMI) and unstable angina (UA)) may be differently affected by BTs [3]. As the pathogenesis of STEMI, as compared to NSTE-ACS, rely mainly on erythrocyte-rich red thrombus formation, it is plausible that infusion of packed red-blood cells may increase the risk of re-AMI in these patients more than in NSTE-ACS patients, even if no clinical data can corroborate this assumption [9].

We conducted the present study with the aim to investigate the occurrence of in-hospital re-AMI and the short-term mortality in patients hospitalized for ACS exposed to BTs. Moreover, our objective was also to assess if BTs may lead to different clinical outcomes in patients with STEMI as compared to those with NSTE-ACS.

Section snippets

Study population

The present study is a sub-analysis of the BleeMACS project, a voluntary contemporary quality improvement international registry, which enrolled 15,401 consecutive unselected patients undergoing percutaneous coronary intervention (PCI) for ACS and who survived the in-hospital phase. Full study protocol has been already published [10], and more detailed data can be found in the BleeMACS webpage (http://bleemacs.wix.com/registry) and in clinicaltrials.gov (Identifier: NCT02466854). Briefly,

Baseline features

After excluding 1426 patients due to the absence of data pertaining in-hospital treatment with BTs, 13,975 patients were included in the present analysis, of whom 10,651 (76.2%) were males, with a mean age of 64.1 ± 12.7 years. BTs during index hospitalization were administered to 465 (3.3%) patients.

As shown in Table 1, patients treated with BTs were older, more frequently of female sex and were characterized by a higher burden of CV risk factors and comorbidities. Dyslipidemia was more frequent

Discussion

The main findings of our study are:

1)
BTs are associated with a higher risk of in hospital reAMI in patients presenting with ACS
2)
BTs relate to an increased risk of reAMI only in patients presenting with STEMI and not in those presenting with NSTE-ACS. This finding highlights a potential peculiar mechanism of harm in these patients.
3)
BTs increase 30-day mortality in both STEMI and NSTE-ACS patients.

BTs are a known factor associated with unfavorable prognosis in patients presenting with ACS. A

Limitations

This is a retrospective, registry-based study, whose findings should warrant confirmation in a prospective setting. The main limitation of the present analysis is the lack of the Hb value at which BTs were performed. However, the main objective of the analysis was to compare the outcome of different presentations of ACS: considering that the main guidelines provided by the scientific societies do not differentiate cut-offs for BTs based on clinical presentation of ACS and that STEMI and

Conclusions

BTs may increase the risk of in hospital reAMI in patients presenting with STEMI and not in those presenting with NSTE-ACSA. Thirty-day mortality is increased by BTs in both patients with diagnosis of STEMI and NSTE-ACS. Our results suggest that a more restrictive approach to BTs could be more beneficial to STEMI patients as compared to NSTE-ACS patients.

Grant support

None.

Conflicts of interest/financial disclosures

The authors report no relationships that could be construed as a conflict of interest.

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Cited by (14)

Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial
2020, International Journal of Cardiology
Citation Excerpt :
There might be some heterogeneity in the effect of transfusion in ACS patients according to different clinical characteristics. Recent observational data suggest worse outcome in patients with RBC transfusion only in case of STEMI but no difference in case of NSTEMI [8]. To the best of our knowledge, a differential effect of transfusion according to the presence of active bleeding has never been explored.
The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI).
The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status.
12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001).
In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.
Impact of decreased ankle-brachial index on 30-day bleeding complications and long-term mortality in patients with acute coronary syndrome after percutaneous coronary intervention
2019, Journal of Cardiology
Citation Excerpt :
The combination of adjunct pharmacologic therapies and percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) frequently results in peri-procedural bleeding complications [1]. Furthermore, several studies have reported that in-hospital bleeding complications in patients undergoing PCI may also increase the short- and long-term mortality, suggesting a biological effect from hemodynamic compromise and blood transfusion [2–6]. Thus, identifying individuals at higher risk of bleeding complications and subsequently aggressively addressing modifiable risk factors among this population may further improve both the health and economic outcomes.
Although concomitant peripheral artery disease in patients with acute coronary syndrome (ACS) has been considered as a high-risk subgroup with a greater incidence of bleeding after percutaneous coronary intervention (PCI), few data exist regarding the clinical utility of the ankle-brachial index (ABI) for predicting bleeding complications, which affects the subsequent outcome.
Eight hundred and twenty-four consecutive patients with ACS who underwent PCI and ABI examination were analyzed retrospectively. Decreased-ABI was defined as ABI <0.9. The primary outcome was bleeding complications within 30 days, which was defined according to the Bleeding Academic Research Consortium classification grade ≥3. The secondary endpoint was all-cause death during follow-up.
Of the 824 patients with ACS, 137 (16.6%) exhibited decreased-ABI. The incidence of bleeding complications was significantly higher in patients with decreased-ABI, compared with the remaining patients (21.9% vs. 6.0%, p < 0.001). In multivariate analysis, anemia [odds ratio (OR) 2.14], estimated glomerular filtration rate < 60 mL/min/1.73 m² (OR 2.14), femoral access (OR 3.31), use of an intra-aortic balloon pump (OR 3.16), and decreased-ABI (OR 2.58) were independent predictors of 30-day bleeding complications. Assigning 1 point for each variable, we developed a new bleeding risk score (range, 0–5). The area under the receiver-operating characteristic curve for the probability of 30-day bleeding for the new risk score was significantly superior than that of the traditional one (0.82 vs. 0.76, p < 0.05). During the median 4-year follow-up, there were 98 incidents of all-cause death. Multivariate Cox-proportional hazard analysis revealed that decreased-ABI [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.15–3.13, p < 0.05] and 30-day bleeding (HR 3.00, 95% CI 1.76–4.97, p < 0.001) were associated with an increased risk of all-cause mortality.
Assessment of ABI provides useful information for predicting 30-day bleeding complications and long-term mortality in patients with ACS after PCI.
Incidence and predictors of bleeding in ACS patients treated with PCI and prasugrel or ticagrelor: An analysis from the RENAMI registry
2018, International Journal of Cardiology
Citation Excerpt :
Dual-antiplatelet therapy with an oral P2Y12 receptor inhibitor is a cornerstone of treatment in patients with ACS undergoing PCI [6–8]. Prasugrel and ticagrelor as compared with clopidogrel have been associated with a significantly reduction in cardiovascular death, myocardial infarction and stroke, although a significant increase in the risk of major bleeding, including fatal one, for prasugrel and in the rate of non CABG-related bleedings for ticagrelor, has been reported [9,10]. In general, hemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS [11–13], and major bleeding is currently one of the most common non-cardiac complications in these patients [13,14].
To evaluate “real life” incidence and independent predictors of major bleeding defined in ACS patients treated with PCI and current standard antithrombotic therapy with prasugrel or ticagrelor.
The RENAMI project is a multicenter retrospective observational registry enrolling 4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin. Primary endpoint was MACE (major adverse cardiovascular events). Secondary endpoints included each component of MACE, cardiovascular death (CV death), recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out of hospital major bleedings after 14.1 ± 6.2 months. These patients had higher rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p < 0.001). Independent predictors of major bleeding were age >75 years (OR 2.00; 95% CI 1.18–3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02–2.70; p = 0.041). BARC 3–5 bleeding was independently associated with all-cause mortality (OR 3.46; 95% CI 1.64–7.31; p 0.001).
In ACS patients treated with PCI and ticagrelor or prasugrel, BARC 3–5 bleedings despite being uncommon negatively impacted on prognosis. Old and female patients are at increased risk, offering clinical indications for tailoring dual antiplatelet therapy.
Gender-related differences in post-discharge bleeding among patients with acute coronary syndrome on dual antiplatelet therapy: A BleeMACS sub-study
2018, Thrombosis Research
Citation Excerpt :
Those were heretofore studied mainly in periprocedural period, thus lack of specific data on bleeding after hospital discharge in a long-term with particular reference to gender disparities. BleeMACS project is a unique source of information concerning real-life ACS treatment and specifically offers insight into bleeding incidents up to one year after discharge in all-comers. [15–20] The aim of proposed study was therefore to evaluate gender-related differences in post-discharge bleeding among patients with ACS respectively to the DAPT regimen.
Bleeding is an independent risk factor of mortality in patients with acute coronary syndromes (ACS). BleeMACS project focuses on long-term bleeding events after hospital discharge, thus we evaluated gender-related differences in post-discharge bleeding among patients with ACS.
We investigated 13,727 ACS patients treated with percutaneous coronary intervention and discharged on dual antiplatelet therapy (either with clopidogrel or prasugrel/ticagrelor). Endpoint was defined as intracranial bleeding or any other bleeding leading to hospitalization and/or red blood transfusion.
Post-discharge bleeding was reported more frequently in females as compared with males (3.7% vs. 2.7%, log-rank P = 0.001). Females (n = 3165, 23%) were older compared to men (69.0 vs. 61.5 years, P < 0.001) and with more comorbidities. Hence, in multivariate analysis female sex was not identified as an independent risk factor of bleeding (HR 1.012, CI 0.805 to 1.274, P = 0.816). Administration of newer antiplatelet agents compared to clopidogrel was associated with over twofold greater bleeding rate in females (7.3% vs. 3.5%, log-rank P = 0.004), but not in males (2.6% vs. 2.7%, log-rank P = 0.887). Differences among females remained significant after propensity score matching (7.2% vs 2.4%, log-rank P = 0.020) and multivariate analysis confirmed that newer antiplatelet agents are independent risk factor for bleeding only in women (HR 2.775, CI 1.613 to 4.774, P < 0.001).
Bleeding events occurred more frequently in women, but female sex itself was not independent risk factor. Administration of newer antiplatelet agents was identified as independent risk factor of bleeding after hospital discharge in female gender, but not in male patients.
Restrictive versus liberal red cell transfusion strategies in patients with acute myocardial infarction: a systematic review and meta-analysis
2021, Research Square
Incidence and clinical outcomes of bleeding complications and acute limb ischemia in STEMI and cardiogenic shock
2021, Catheterization and Cardiovascular Interventions

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^☆: All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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Impact of blood transfusion on in-hospital myocardial infarctions according to patterns of acute coronary syndrome: Insights from the BleeMACS registry☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Baseline features

Discussion

Limitations

Conclusions

Grant support

Conflicts of interest/financial disclosures

Am. J. Cardiol.

Rev. Port. Cardiol.

J. Am. Coll. Cardiol.

Am. Heart J.

JACC Cardiovasc. Interv.

JACC Cardiovasc. Interv.

J. Am. Coll. Cardiol.

Int. J. Cardiol.

Association of hemoglobin levels with clinical outcomes in acute coronary syndromes

Circulation

Prevalence and non-invasive predictors of left main or three-vessel coronary disease: evidence from a collaborative international meta-analysis including 22 740 patients

Heart

Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis

JAMA Intern. Med.

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group

N. Engl. J. Med.

Patterns and outcomes of red blood cell transfusion in patients undergoing percutaneous coronary intervention

JAMA

Discontinuation of dual antiplatelet therapy over 12 months after acute coronary syndromes increases risk for adverse events in patients treated with percutaneous coronary intervention: systematic review and meta-analysis

J. Interv. Cardiol.

Transfusion and mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Eur. Heart J.