Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis

BACKGROUND Despite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI. METHODS Database searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events. RESULTS Forty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects. CONCLUSIONS The intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen.