Duarte, GS;
Nunes-Ferreira, A;
Brogueira Rodrigues, F;
Pinto, F;
Ferreira, JJ;
Costa, J;
Caldeira, D;
(2019)
Morphine in acute coronary syndrome: systematic review and meta-analysis.
BMJ Open
, 9
(3)
, Article e025232. 10.1136/bmjopen-2018-025232.
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Abstract
Objective: Morphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised trials (RCTs) and observational studies to synthesise the available evidence. Design: Systematic review and meta-analysis. Data sources: CENTRAL, MEDLINE, EMBASE, and trial registries. Eligibility criteria for selecting studies: We included RCTs and observational studies evaluating the impact of morphine in cardiovascular outcomes or platelet reactivity measures. Data extraction and synthesis: Data was screened, extracted, and appraised by 2 independent reviewers. The data was pooled results using a random-effects model. Outcomes included in-hospital mortality, major adverse cardiovascular events (MACE), platelet reactivity (using VerifyNow®), and bleeding, reported as relative risk (RR) with 95% confidence intervals (95% CI). We assessed the confidence in the evidence using the GRADE framework. We followed the MOOSE and PRISMA guidelines. Results: Five RCTs and 12 observational studies were included, enrolling 69,993 participants. Pooled results showed an increased risk of in-hospital mortality (RR 1.45 [95% CI 1.10-1.91], low GRADE confidence), MACE (RR 1.21, 95% CI 1.02 to 1.45), and an increased platelet reactivity at 1 and 2 hours (59.37 platelet reactivity units (PRU), 95% CI 36.04 to 82.71; 68.28 PRU, 95% CI 37.01 to 99.55; high GRADE confidence) associated with morphine. We found no significant difference in the risk of bleeding. We found no differences in subgroup analyses based on study design and ACS subtype. Conclusions: Morphine was associated with an increased risk of in-hospital mortality and MACE but the high risk of bias leads to low result confidence. There is high confidence that morphine decreases the antiplatelet effect of P2Y12 inhibitors. Registrations number: PROSPERO CRD42016036357.
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