Table 2.

Characteristics of the non-randomised studies

Study	Location, study design	Follow-up (years)	Patients	Antiplatelet medication used	Morphine characteristics	Comparator	N	Mean age (SD)	Outcome measures	Ascertainment		Outcome adjustments for confounders
										Drug use	Outcomes
Bellandi et al36	Italy, Greece, prospective	2	STEMI patients undergoing PPCI and receiving either prasugrel or ticagrelor	NR	6±3 mg, no additional information	No intervention	182	64 (13)	Myocardial reperfusion by early ST-segment resolution	According to the physician’s decision	Operator blinded to morphine use	NR
Bonin et al41	France, retrospective	1	STEMI	NR	NR	No intervention	969	60 (13)	MACE	According to the physician’s decision	NR	Adjusted for baseline patient clinical risk factors
Danchin et al42	France, retrospective	1	STEMI	DAPT NR	NR	No intervention	3548	63 (12)	All-cause mortality	According to the physician’s decision	NR	NR
Farag et al43	UK, prospective single centre	30 days	STEMI	DAPT 97.0% Aspirin 79.0% Ticagrelor 17.3% Clopidogrel 0.7% Prasugrel	5–10 mg IV	No intervention	300	64 (13)	MACE and major bleeding	According to the physician’s decision	NR	NR
Franchi et al45	USA, posthoc analysis of RCT	1	STEMI patients undergoing PPCI	Aspirin and ticagrelor	NR	No intervention	46	59	Asses the pharmacokinetic and pharmacodynamics of escalating doses of ticagrelor	According to the physician’s decision	VerifyNow and VASP assays	Baseline Platelet reactivity unit values
Grendahl and Hansteen38	Norway, prospective	NR	Uncomplicated AMI<48 hour of symptoms	NR	150 mg IV single dose	Placebo	20	NR	Assess the circulatory effects of morphine	NR	NR	NR
Johnson et al40	UK, posthoc analysis	1.5	STEMI	Aspirin and prasugrel	NR	No intervention	106	61.1 (11.7)	Platelet reactivity	According to the physician’s decision	Multiplate assay	NR
McCarthy et al44	USA, retrospective	Hospital stay	STEMI and NSTE-ACS	Insufficient detail	NR	No intervention	3027	62 (12)	Mortality	According to the physician’s decision	NR	Adjusted for baseline patient clinical risk factors and interventions used
Meine et al34	USA, retrospective	2.5	NSTEMI	Insufficient detail	IV, no additional information	No intervention	57 039	68	Assess in-hospital death, recurrent myocardial infarction, congestive heart failure, cardiogenic shock	According to the physician’s decision	CRUSADE database	Adjusted for baseline patient clinical risk factors, for provider and hospital characteristics
Puymirat et al35	France, Retrospective	2 months	STEMI patients with symptoms<48 hour	· 50% Aspirin · 71% Clopidogrel · 8% Prasugrel	NR	No intervention	2438	63	Assess practices for myocardial infarction management in ‘real llife’ and with medium and long-term outcomes	According to the physician’s decision	FAST-MI 2010 database	Adjusted for baseline characteristics of the patients
Siller-Matula et al39	Austria, prospective	2	STEMI patients treated with in-hospital loading dose of prasugrel	Aspirin and prasugrel	5–15 mg IV single dose	No intervention	32	60 (11)	Assess if abciximab is a bridging therapy to achieve adequate levels of platelet inhibition	NR	Multiplate	NR
Silvain et al10 (ATLANTIC study)	International, posthoc analysis of RCT	14 hours	STEMI	Aspirin and ticagrelor	NR	No intervention	37	56.2 (10.2)	Assess coronary reperfusion prior to percutaneous coronary interven- tion with prehospital or in-hospital ticagrelor 180 mg loading dose	NR	VerifyNow assay	NR

AMI, acute myocardial infarction; DAPT, dual antiplatelet therapy; IV, intravenous; MACE, major adverse cardiovascular events; NR, not reported; NSTE-ACS, non-ST elevation acute coronary syndrome; NSTEMI, non-ST elevation myocardial infarction; PPCI, primary percutaneous coronary intervention; RCT, randomised controlled trial; STEMI, ST elevation myocardial infarction; VASP, vasodilator-stimulated phosphoprotein.