Is restrictive transfusion too restrictive in acute coronary syndromes with anemia? A meta-analysis of early and mid-term randomized outcomes

Background Restrictive transfusion thresholds (haemoglobin [Hb] 7–8 g/dL) are widely implemented across acute care settings. However, acute coronary syndromes (ACS) represent a pathophysiological state characterized by impaired myocardial oxygen delivery and heightened ischemic vulnerability. Whether allowing Hb to fall to restrictive levels is biologically neutral in ischemic myocardium remains uncertain. Contemporary ACS guidelines state that transfusion to achieve Hb ≥10 g/dL may be reasonable in selected patients (Class IIb), underscoring persistent clinical equipoise. Importantly, most prior analyses have emphasized short-term outcomes without evaluating potential divergence over longer follow-up. Purpose To evaluate the impact of liberal versus restrictive transfusion strategies on both early (1-month) and mid-term (6–12-month) outcomes in patients with ACS and anemia. Methods We performed a systematic review and random-effects meta-analysis of randomized controlled trials comparing liberal (Hb trigger approximately 10 g/dL) versus restrictive (Hb trigger 7–8 g/dL) transfusion strategies in ACS or acute myocardial infarction populations. Early endpoints included all-cause mortality, death plus myocardial infarction (MI), and major adverse cardiovascular events (MACE) at 1 month. Mid-term endpoints were all-cause mortality and MACE at 6–12 months. Risk ratios (RR) were pooled using Mantel–Haenszel random-effects models. Results Five randomized datasets comprising approximately 4,500 patients were included for early analyses; four contributed to mid-term follow-up. At 1 month, liberal transfusion was not associated with a statistically significant reduction in all-cause mortality (RR 0.90;95% CI 0.57–1.41; I²=47.9%), death plus MI (RR 0.90;95% CI 0.55–1.46; I²=54.6%), or MACE (RR 0.91;95% CI 0.62–1.35; I²=48.8%). However, point estimates consistently favoured liberal transfusion across all early ischemic endpoints. At 6–12 months, liberal transfusion demonstrated a sustained directional reduction in ischemic events, with all-cause mortality RR 0.92(95% CI 0.82–1.04; I²=0%) and MACE RR 0.85(95% CI 0.69–1.04; I²=0%), with complete absence of heterogeneity. Conclusions Restrictive transfusion did not demonstrate superiority over liberal transfusion for early mortality or ischemic outcomes in ACS with anemia. However, a consistent signal toward lower mid-term ischemic events was observed with liberal transfusion, without evidence of excess harm. The pattern of early neutrality followed by mid-term divergence suggests that maintaining higher haemoglobin levels during the acute ischemic phase may improve myocardial oxygen delivery and influence longer-term cardiovascular outcomes. These findings indicate that transfusion thresholds in ACS may require disease-specific consideration rather than uniform extrapolation from general critical-care practice.1-month outcomes6-12 months outcomes