Haemoglobin drop ups death risk in hospitalized ACS patients

In-hospital decreases in haemoglobin (Hb) levels ≥3 g/dl is prevalent among patients with acute coronary syndrome (ACS) managed invasively and appears to increase the risk for 1-year mortality even in the absence of overt bleeding, according to a study.

“A declining Hb level may be a useful surrogate for other bleeding-related endpoints in clinical trials investigating treatment strategies for patients with ACS undergoing invasive management,” the researchers said.

This study categorized patients by the presence and amount of in-hospital Hb drop based on baseline and nadir Hb values. They were further stratified by the occurrence of adjudicated in-hospital bleeding. Hb drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl).

Multivariate Cox regression was used to examine the association between Hb decrease and mortality in patients with and without overt bleeding.

A total of 7,781 patients alive after 24 h following randomization had available Hb data, of whom 6,504 patients (83.6 percent) had Hb drop. In this population, 5,756 (88.5 percent) did not have overt bleeding and 748 (11.5 percent) had. [J Am Coll Cardiol 2021;77:375-388]

Among those without overt bleeding, minor (hazard ratio [HR], 2.37, 95 percent confidence interval [CI], 1.32–4.24; p=0.004) and major (HR, 2.58, 95 percent CI, 0.98–6.78; p=0.054) Hb drop each correlated with higher 1-year mortality.

Furthermore, the association of minor and major Hb drop with 1-year mortality was directionally similar among patients with overt bleeding, but the CIs appeared to be wider (minor: HR, 3.53, 95 percent CI, 1.06–11.79; major: HR, 13.32, 95 percent CI, 3.01–58.98).

“If confirmed, these results may help the identification of higher risk patients and inform contemporary bleeding definitions,” the researchers said.

Several mechanisms could explain in-hospital Hb decrease in ACS patients. Overt bleeding muddles the hospital course because of pharmacological and invasive procedures. Subtle bleeding can also occur due to the aggressive antithrombotic burden, with the primary bleeding source staying hidden if not investigated appropriately. [J Am Coll Cardiol 2011;58:1750-1756; Eur Heart J 2009;30:1457-1466]

In addition, Hb drop after ACS could have been driven by the following: blood loss during the index procedure, intense inflammatory status, stress polycythemia on admission, haemodilution secondary to volume repletion, or impaired bone marrow activity due to clinical factors. [Am Heart J 2005;149:619-626; Circulation 1975;51:1079-1084; Am J Cardiol 1993;71:869-872; Eur Heart J 2007;28:1289-1296]

In the early phase of ACS, anaemia was found to consistently correlate with bleeding complications. [Eur Heart J 2003;24:1815-1823; Lancet 2017;389:1025-1034]

However, its prognostic impact could extend to nonbleeding outcomes and death, possibly by worsening myocardial ischaemic insult, increasing myocardial oxygen demand, and inducing abnormal neurohormonal activation and cardiac remodeling. [Circulation 2005;111:2042-2049; Circulation 1986;74:1085-1092; J Trauma Inj Infect Crit Care 1996;41:416-423; Circulation 2004;110:149-154]

“Previous studies showed that the presence of low Hb levels before and/or after percutaneous coronary intervention is a powerful and independent predictor of future cardiovascular events,” the researchers said. [Circulation 2005;111:2042-2049; J Cardiovasc Transl Res 2020;13:618-628; J Am Heart Assoc 2019;8:e013703]