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

Abstract

BackgroundDespite 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.MethodsDatabase 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.ResultsForty-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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12872-017-0722-z) contains supplementary material, which is available to authorized users.

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis

“…However, a previous meta-analysis suggesting that nicorandil helps to reduce all-cause mortality and cardiovascular events in patients with ischemic heart disease [35] and reduce myocardial injury and the incidence of adverse reactions to PCI in the Chinese population [36] has reignited interest in this agent. To date, the long-term benefits of nicorandil when combined with primary PCI in patients with STEMI have been uncertain [32,37], which prompted us to perform this meta-analysis. To our knowledge, this is the first metaanalysis investigating both the short-and long-term effects of combining nicorandil with primary PCI in patients with STEMI.…”

Fenómeno de no reflujo en la angioplastia coronaria: incidencia, características clínico-angiográficas y eficacia del tratamiento

“…Tres metaanálisis recientes permiten concluir que la adenosina intracoronaria utilizada en pacientes con SCAcST tratados con ATC primaria se asocia con menor incidencia de flujo TIMI <3 y mayor frecuencia de renivelación del segmento ST (28)(29)(30) . El metaanálisis de red de Niu y colaboradores evaluó el efecto de siete agentes farmacológicos de uso intracoronario (adenosina, anisodamina, diltiazem, nicorandil, nitroprusiato, urapidil y verapamil) sobre el NR en pacientes con SCAcST tratados con ATC primaria.…”

“…El metaanálisis de red de Niu y colaboradores evaluó el efecto de siete agentes farmacológicos de uso intracoronario (adenosina, anisodamina, diltiazem, nicorandil, nitroprusiato, urapidil y verapamil) sobre el NR en pacientes con SCAcST tratados con ATC primaria. En lo que se refiere a la adenosina, si bien este metaanálisis comprobó mejoría del flujo coronario, no demostró mejoría de la fracción de eyección ventricular izquierda, ni disminución de efectos cardiovasculares adversos con el uso de la adenosina (30) . Estos resultados negativos del metaanálisis podrían justificarse por la inclusión del estudio randomizado REFLO-STEMI, que comparó la eficacia de dosis consideradas como altas de adenosina (2-3 mg) versus nitroprusiato (500 mg) para reducir el tamaño del infarto o la oclusión microvascular determinados por resonancia magnética cardíaca.…”

“…Existen nuevas opciones terapéuticas para el NR, como la anisodamina (agente antimuscarínico, bloqueador de sobrecarga celular de calcio, de la superoxidación lipídica y de la formación de radicales libres), que ha demostrado mejorar el flujo coronario epicárdico y la resolución del segmento ST, así como la fracción de eyección del ventrículo izquierdo y reducir eventos cardiovasculares adversos, como lo demuestra el metaanálisis de Niu y colaboradores (30) . En este metaanálisis sobre 42 estudios randomizados y 4.069 pacientes, la anisodamina mostró la mejor performance entre siete drogas estudiadas, incluyendo la adenosina.…”

Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention

“…Finding an effective way to prevent the occurrence of MNR following PCI is an urgent problem currently awaiting a solution. Many interventions to improve myocardial perfusion have been trialled, including mechanical methods such as distal devices and thrombus aspiration devices, and pharmacological methods, such as platelet glycoprotein GPIIb/IIIa antagonists and vasodilators …”