Why the study?
Normal glucose-insulin-potassium (GIK) did not improve clinical outcomes in ACS patients in the reperfusion era, leaving it uncertain whether high-dose GIK provides cardioprotective benefits.
Does high-dose glucose-insulin-potassium (GIK) reduce major adverse cardiovascular events in acute coronary syndrome patients undergoing reperfusion therapy?
Does high-dose glucose-insulin-potassium (GIK) reduce major adverse cardiovascular events in acute coronary syndrome patients undergoing reperfusion therapy?
High-dose GIK as an adjunct to reperfusion therapy in ACS patients reduces MACEs and heart failure but increases the risk of phlebitis, hyperglycemia, and hypoglycemia without improving all-cause mortality.
High-dose GIK was associated with fewer MACEs in reperfused ACS; hypothesis-generating and requires prospective RCT confirmation before practice change.
Background : Normal glucose-insulin-potassium (GIK) did not improve clinical outcomes in ACS patients in today’s reperfusion era; however, whether high-dose GIK appeared any cardioprotective function remains uncertain. This meta-analysis aimed to assess the efficacy of high-dose GIK on clinical outcomes in acute coronary syndrome (ACS) patients undergoing reperfusion therapy. Methods : We searched PubMed, Web of science, MEDLINE, Embase and Cochrane Library databases from inception until April 26, 2022 for randomized controlled trials (RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints were all-cause mortality, left ventricular ejection fraction (LVEF), heart failure, reinfarction, phlebitis, hyperglycemia, hyperkalemia, hypoglycemia, secondary reperfusion, serum glucose and potassium, activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Results : Eleven RCTs with 884 patients were eventually included. Compared with placebos, high-dose GIK markedly reduced MACEs (RR 0.57, 95%CI 0.35 to 0.94, p<0.05) and the risk of heart failure (RR 0.48, 95%CI 0.25 to 0.95, p <0.05), also improved LVEF (MD 2.12, 95%CI 0.32 to 3.92, p<0.05) at 6 months. However, no difference was observed in occurring all-cause mortality at 30 days (RR 0.90, 95%CI 0.35 to 2.28, p=0.82) or 1 year (RR 0.57 95%CI 0.22 to 1.51, p=0.26). Additionally, high-dose GIK was significantly associated with higher occurrence of phlebitis (RR 4.78, 95%CI 1.36 to 16.76, p<0.05), hyperglycemia (RR 9.06, 95%CI 1.74 to 47.29, p<0.01) and hypoglycemia (RR 6.50, 95%CI 1.28 to 33.01, p<0.05), but not reinfarction (RR 0.74, 95%CI 0.36 to 1.50, p =0.40), hyperkalemia (RR 5.99, 95%CI 0.79 to 45.27, p=0.08) or secondary reperfusion (RR 0.91, 95%CI 0.72 to 1.14, p=0.41). As for oxidative stress-lowering function, high-dose GIK markedly reduced SOD activity (SMD -0.77, 95%CI -1.28 to -0.26, p<0.05), but not activity of GSH-Px (SMD 0.34, 95%CI -0.16 to 0.83, p=0.18) or CAT (SMD 0.35, 95%CI -0.14 to 0.84, p=0.16). Conclusions: Patients with ACS receiving reperfusion therapy showed reduction in MACEs and heart failure, improvement of LVEF, as well as good oxidative stress-lowering efficacy in response to high-dose GIK. Simultaneously, higher occurrence of several complications such as phlebitis, hyperglycemia and hypoglycemia accompanied, also a trend to an increase in serum potassium appeared. Furthermore, patients’ all-cause mortality did not modulate any benefits associated with exposure to high-dose GIK. More trails with long-term follow-up are stilled demanded to further verify its efficacy and security to provide powerful evidences for clinical practice.
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Liu et al. (2022) studied this question.
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