Acute coronary syndrome (ACS) is a disease that is caused by an obstruction of coronary arteries, which results in decreased blood supply in the myocardium. ACS needs immediate critical care, and often a time challenging event. The first goal of managing patients with ACS in the emergency department is to bring the patient to catheterization intervention in 90 min known as door-to-balloon time. Because platelet inhibition plays a key role in preventing acute thromboembolic events and ischemic complications amongst patients with ACS [1], clinicians usually need to initiate antiplatelet therapy simultaneously or before percutaneous coronary intervention to reduce acute ischemic complications and recurrent thrombotic events [2]. For instance, a randomized controlled trial (RCT) has reported that aspirin significantly prevents non-fatal reinfarction and non-fatal stroke with around a 50% reduction rate. Furthermore, it is not associated with any significant increase in cerebral hemorrhage or bleeds requiring transfusion [3]. Thus, antiplatelet therapy is considered to be needed in both short and long-term use to prevent secondary myocardial injuries [4]. Besides, mortality is reduced when a P2Y inhibitor is added alongside aspirin by 9% with non-significant increased fatal bleeding, which includes cerebral hemorrhage and bleeding that needs a transfusion [5]. Consequently, physicians in critical care for ACS commonly prescribe aspirin and P2Y inhibitor together.

However, morphine is sometimes prescribed for patients with ACS in some conditions such as in the setting of severe chest pain and increased sympathetic tone caused by ACS. In these situations, morphine rapidly relieves symptoms, opioids are now a mainstay in controlling ischemic chest pain [[6], [7], [8]]. Unlike non-steroid anti-inflammatory drugs, morphine has a relatively less cardiovascular adverse effect which is the ultimate reason clinicians usually choose morphine instead of other analgesics to deal with pain control [[9], [10], [11]]. With its analgesic and sedative properties, morphine is theoretically believed to reduce myocardial oxygen demand. Through stabilizing oddly stimulated sympathetic tone in patients. It can lighten the work of breathing, anxiety, will eventually ventricular workloads [12,13].

Briefly, P2Y inhibitors and morphine are widely used in caring for patients with ACS. Morphine is even known to be a recommended protocol for ACS by Cardiology (ACC)/American Heart Association (AHA) for pain relief. Taking the abovementioned issues into consideration, however, there have been some concerns about the combined use of morphine and platelet inhibitors due to their interaction in metabolism. In pharmacodynamic studies, patients who administered both agents together resulted in delayed time to reach peak blood concentration of P2Y inhibitors [14]. However it is still controversial in clinical practice if opioids blunt antiplatelet activity. In the present study, therefore, we aimed to examine whether using morphine with antiplatelets in patients with ACS affects the clinical outcomes based on currently available evidence. The research question of this study was structured in PICO format as follows:

P: Patients with ACS.

I: antiplatelet therapy with morphine.

C: P2Y inhibitor without morphine.

O: Overall mortality, major adverse cardiac events (MACE), major bleeding, and length of hospital stay.