The management of myocardial infarction includes complementary pharmacotherapy for pain relief and cardioprotection. |
The safety and efficacy of some commonly used treatments have been questioned by recent evidences. |
Considering the interaction between opioids and oral P2Y12 inhibitors, morphine administration should be reserved for those patients having persistent severe chest pain despite alternative analgesics which avoid opioids. |
Considering the results of therapies for cardioprotection, many drugs should not be part of routine standard care, but they should be wisely and selectively administered. |
Future research efforts need to focus on novel therapeutic approaches for improving clinical outcomes. |
In the current era of ST elevation myocardial infarction (STEMI) treatment, the “as soon as possible” therapies (“ASAP”) remain Aspirin, Second antiplatelet agent, Anticoagulant and of course Primary percutaneous coronary intervention. |
1 Introduction
2 Early Pharmacological Treatment
2.1 Relief of Pain: Opioids
2.1.1 Interaction Between Opioids and P2Y12 Inhibitors
Trial | Year | N of patients | Randomization | Drug administration | Endpoints | Results of endpoints |
---|---|---|---|---|---|---|
Hobl et al. [5] | 2014 | 24 | Morphine vs placebo | Morphine 5 mg | AUC of clopidogrel active metabolite | Morphine reduced the AUC of clopidogrel active metabolite 34%, p = 0.001 |
IMPRESSION trial [6] | 2016 | 70 | Morphine vs placebo | Morphine 5 mg | AUC(0–12) for ticagrelor during the first 12 h after the administration of the LD | Ticagrelor 6307 ± 4359 vs. 9791 ± 5136 ng h/mL in morphine vs placebo; a difference of 36%, p = 0.003 |
PACIFY trial [7] | 2017 | 70 | Fentanyl vs routine care | IV fentanyl (dose at the discretion of treating providers) | Ticagrelor concentration during the 24 h after loading as assessed by the AUC(0–24) | 2107 vs 3301 ng·h−1 mL in fentanyl vs no fentanyl, p = 0.05 |
PERSEUS trial [8] | 2020 | 38 | Fentanyl vs morphine | IV fentanyl (50–100 μg) or IV morphine (4–8 mg) | Platelet reactivity at 2 h after ticagrelor LD | At 2 h, mean P2Y12 reaction units were 173.3 ± 89.7 and 210.3 ± 76.4 in patients treated with fentanyl and morphine, p = 0.463 |
ON-TIME 3 trial [9] | 2020 | 195 | Acetaminophen vs fentanyl | Paracetamol (1000 mg) or fentanyl titrated based on the weight of the patient | Level of PRU measured immediately after primary PCI in patients treated with ticagrelor | Median PRU 104 (IQR 37–215) for acetaminophen vs. 175 (63–228) for fentanyl, p = 0.18 |
2.1.2 Alternative Analgesics that Avoid Opioids
2.2 Oxygen
2.3 Nitrates
3 Cardioprotective Pharmacotherapy
3.1 Beta-Blockers
Trial | Year | N of patients | Randomization | Drug administration | Endpoints | Results of endpoints | |
---|---|---|---|---|---|---|---|
Hanada et al. [29] | 2012 | 96 | Non-blinded, open-label, no placebo (routine care) | Landiolol 3 μg/kg/min infusion for 24 h after PCI | LV function assessed by left ventriculography during the acute phase and during a 6-month follow-up | LVEF increased from 49.1 ± 1.5% to 52.0 ± 1.5% in the chronic phase (p = 0.01) in the landiolol group, no significant difference was found in the control group (from 50.2 ± 1.4% to 50.2 ± 1.2%) | + |
METOCARD-CNIC trial [31] | 2013 | 270 (220 with CMR) | Single-blind, no placebo (routine care) | IV metoprolol 15 mg during transfer to PCI or at the emergency department | Infarct size by CMR (extent of myocardial necrosis quantified by delayed gadolinium enhancement) performed 5 to 7 days after STEMI | Adjusted difference, −6.52 in metoprolol group (95% CI −11.39 to −1.78; p = 0.012) | + |
BEAT-AMI trial [30] | 2016 | 101 | Single-blind, placebo-controlled | Esmolol infusion after PCI | Maximum change in troponin T from baseline to 48 h | Median troponin T concentration increased from 0.2 to 1.3 ng/mL in the esmolol group and from 0.3 to 3.2 ng/mL in the placebo group (p = 0.01) | + |
EARLY-BAMI trial [32] | 2016 | 683 (342 with CMR) | Double-blind, placebo-controlled | Metoprolol IV doses of 5 mg. First bolus in ambulance. Second bolus immediately before PCI | Myocardial infarct size as measured by CMR at 30 days | Infarct size (percent of LV) 15.3 ± 11.0% in metoprolol group and 14.9 ± 11.5% in placebo group (p = 0.616) | − |
3.2 Adenosine and Other Coronary Vasodilators
Authors | Year | N of patients | Randomization | Administration | Endpoints | Results of endpoints |
---|---|---|---|---|---|---|
Marzilli et al. [36] | 2000 | 54 | Adenosine:placebo | IC distal to occlusion during balloon inflation | Feasibility and safety of IC adenosine administration | + |
Petronio et al. [37] | 2005 | 30 | Adenosine:placebo | IC distal to occlusion during balloon inflation | Left ventricular remodeling at 6 months | − |
Ross et al. [44] (AMISTAD-II trial)* | 2005 | 2118 | Adenosine:placebo | IV within 15 min either of the start of fibrinolysis or before coronary intervention | New CHF, first re-hospitalization for CHF, or death from any cause within 6 months | − |
Infarct size was measured in a subset of 243 patients by technetium-99m sestamibi tomography | + | |||||
Stoel et al. [38] | 2008 | 51 | Adenosine:placebo | IC after last balloon inflation | STR and TIMI frame count, MBG, coronary blood flow, coronary, vascular resistance | + |
Fokkema et al. [43] | 2009 | 448 | Adenosine:placebo | IC after thrombus aspiration and after stenting | The incidence of residual ST-segment deviation (< 0.2 mV) after PCI | − |
Desmet et al. [40] | 2011 | 112 | Adenosine:placebo | IC | Myocardial salvage on CMR 2–3 days post perfusion | − |
Grygier et al. [39] | 2011 | 70 | Adenosine:placebo | IC after crossing the lesion and then after first balloon inflation | ST-segment elevation resolution after PCI; MBG, TIMI flow grade and TIMI frame count at the end of procedure | + |
Zhang et al. [42] | 2012 | 90 | 1:1:1 To receive adenosine low-dose:high-dose:placebo | IV after the guide wire crossed the lesion | Left ventricular function, and infarct size | + |
Wang et al. [41] | 2012 | 69 | Adenosine:placebo | IV prior to stent implantation | Myocardial perfusion and segmental contractile function | + |
Niccoli et al. [47] (REOPEN-AMI trial) | 2013 | 240 | 1:1:1 To receive adenosine: nitroprusside:saline | IC following thrombus aspiration | ST-segment resolution (> 70%) after PCI | + |
Garcia-Dorado et al. [46] | 2014 | 201 | Adenosine:placebo | IC before thrombectomy and direct stenting | Infarct size by late enhancement on CMR imaging performed between 2 and 7 days post-reperfusion | − |
Nazir et al. [49] (REFLO-STEMI trial) | 2016 | 247 | 1:1:1 To receive adenosine:nitroprusside:control (standard primary PCI alone) | IC after thrombectomy and Immediately following stent deployment | Infarct size by CMR performed at 24–96 h | − |