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Título

Interfering of fentanyl in the pharmacodynamics and pharmacokinetics of ticagrelor: A meta-analysis of randomized trials

Resumo

Background
Morphine, are strong analgesics and were used in patients with acute coronary syndrome. Many studies show reducing effects of antiplatelet agents for delaying the intestinal intake of P2Y12 inhibitors and due to their action on gastrointestinal motility. There are many trials using morphine, but only a few using fentanyl as an opioid
We conduct a systematic review(SR) and meta-analysis(MA) that evaluates the pharmacodynamic and pharmacokinetic stages of the use of fentanyl and non-opioid agents in a population using Ticagrelor(TC).
Methods
This SR and MA was conducted in accordance with PRISMA guidelines. We searched PubMed, Embase, and Cochrane Central for studies comparing fentanyl with non-opioids in patients using TC. Statistical analysis was performed using RevMan 5.4.1. The stages of interest were: ticagrelor concentration (CONT), platelet reactivity units (PRU), and the occurrence of nausea and vomiting. To evaluate continuous outcomes, mean difference (MD) was used, and for binary outcomes, odds ratio (OR).
Results
We included three randomized trials(335 patients), of which 168(50.15%) were in the non-opioid group. The average age was 65y. Follow-up time lasted between 7 hours and 30 days. 25.13% of current smoker, 59.83% hypertensive, and 20.8% diabetic. CONT at 1 and 2 hour was significantly higher in the non-opioid group (MD:364.43 ng/ml; 95% CI:205.15-523.73;p<0.00001) Fig1). PRU at 1 hour was not significant between groups (MD: -51.95; 95% CI: -113.73-9.83; p=0.10). In the subgroup analysis, PRU at 2 hours had a significant reduction in the non-opioid arm (MD: -60.0; 95% CI:-91.96-(-28.04);p=0.0002) (fig 2 ). CONT at 2 hours was significantly higher in the non-opioid group(MD:456.65 ng/ml; 95% CI: 205.95-707.37;p=0.0004). The occurrence of nausea and vomiting was 82% lower in the group that did not receive fentanyl(OR:0.18;95% CI:0.06-0.59;p=0.004)

Conclusion
I In this MA with 335 patients, CONT at 1 and 2 hours was significantly higher in the arm that did not use opioids, and PRU at 2 hours had a significant reduction in the non-opioid arm (fig 2). The results suggest a harmful interaction with a reduction in the antiplatelet effect in the concomitant use of fentanyl and TC.

Palavras Chave

Ticagrelor; Fentanyl

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