Table 4. Overview of included studies on the association between guideline adherence and adverse cardiac events.

First author, year (country)	Study design	Sample	Guideline recommendations†					Univariate associations with occurrence of adverse cardiac events‡ Significance level: p≤0.05
			I	II	III	IV
Bhatt, 2004 [24] (USA) [PMID: 15523070]	Prospective, multi-center, observational registry (CRUSADE)§	17,926 NST-ACS patients, enrolled from 248 hospitals			X			Patients who underwent early CA (<48 h after hospital admission) (vs. not receiving early CA) had significantly:      ▪ lower in-hospital mortality (2.0% versus 6.2%, AOR 0.63; 95%CI 0.52-0.77);      ▪ lower composite endpoint of death/MI (4.7% versus 8.9%, AOR 0.79; 95%CI 0.69-0.90)
Dziewierz, 2007 [45] (Poland) [PMID: 17496494]	Prospective, multi-center, observational registry (Malopolska registry of ACS)	807 NSTEMI patients, enrolled from 29 hospitals	X					Being prescribed aspirin, clopidogrel, BB, ACE/ARB and statins (vs. not receiving such therapies) was significantly associated with:      ▪ a lower risk of in-hospital death, as for every unit of increase on the pharmacotherapy index∞ the risk of death decreased by 46.0%
Hoekstra, 2005 [28] (USA) [PMID: 15863399]	Prospective, multi-center, observational registry (CRUSADE)§	56,804 NST-ACS patients, enrolled from 443 hospitals	X					Being prescribed with early GP IIb/IIIa inhibitors (vs. not receiving early GP IIb/IIIa inhibitors) was significantly associated with:      ▪ lower in-hospital mortality (2.7% versus 4.7%)      ▪ lower composite endpoint of death/MI (5.7% versus 7.7%)
First author, year (country)	Study design	Sample	Guideline recommendations†				Univariate associations with occurrence of adverse cardiac events‡ Significance level: p≤0.05
			I	II	III	IV
Lee, 2008 [55] (Canada) [PMID: 18268170]	Prospective, multi-center, observational registry (Canadian ACS II)	2,136 NST-ACS patients, enrolled from 36 hospitals			X		Patients who underwent in-hospital CA (vs. patients not receiving in-hospital CA) had significantly:      ▪ lower in-hospital mortality (0.8% versus 3.7%) and lower 1-year mortality (4.0% versus 10.9%).      ▪ higher rates of MI (6.8% versus 2.4%)      ▪ higher composite endpoint of death/MI (7.1% versus 5.0%). However 1 year after discharge patients had lower rates of death/MI (12.5% versus 16.4%).
Miller, 2007 [29] (USA) [PMID: 17679127]	Prospective, multi-center, observational registry (CRUSADE)§	72,054 NST-ACS patients, enrolled from 509 hospitals	X				Being prescribed acute BB <24 h after admission (vs. not receiving acute BB) was significantly associated with:      ▪ lower in-hospital mortality (3.9% versus 6.9%, AOR 0.66; 95%CI 0.60-0.72)      ▪ lower MI (3.0% versus 3.6%, AOR 0.80, 95%CI 0.72-0.89).
Peterson, 2003 [32] (USA) [PMID: 12849658]	Prospective, multi-center, observational registry (NRMI)§	60,770 NSTEM patients, enrolled from 1189 hospitals	X				Being prescribed with early GP IIb/IIIa inhibitors <24 h after admission (vs. not receiving early GP IIb/IIIa inhibitors) was significantly associated with:      ▪ lower unadjusted mortality (3.3% versus 9.6%), lower adjusted mortality (AOR 0.88; CI95% 0.79-0.97)      ▪ lower death/MI (4.5% versus 10.3%)      ▪ higher rates of MI (1.5% versus 1.1%)
Peterson, 2006 [19] (USA) [PMID: 16639050]	Prospective, multi-center, observational registry (CRUSADE)§	64,775 NST-ACS patients, enrolled from 350 hospitals	X			X	Hospitals with higher guideline adherence rates had significantly:      ▪ lower in-hospital mortality rates (4.15% for highest adherence quartile versus 6.31% for lowest adherence quartile, AOR 0.81; 95%CI 0.68-0.97)      ▪ Every 10% increase in composite adherence score = 10% reduction in mortality rate (AOR 0.90; 95%CI 0.84-0.97)
Abbreviations: ACE, angiotensin-converting-enzyme inhibitor; ACS; acute coronary syndromes; ARB, angiotensin II AT1 receptor blockers; BB, beta-blocker; CA, coronary angiography; CRUSADE, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines; GP IIb/IIIa, Glycoprotein IIb/IIIa receptor inhibitors; MI, myocardial infarction; NST-ACS, Non-ST-Elevation Acute Coronary Syndromes; NSTEMI, non-ST-elevation myocardial infarction; NRMI, National Registry of Myocardial Infarction. †class I guideline recommendation: I = acute pharmacological care (<24 h after admission), II = risk stratification, III = invasive procedures, IV = discharge medications. ‡Only significant associations are presented, and where possible adjusted odds ratios (AOR) and their 95% confidence intervals (CI) are provided. §Concern large registries that provide access to quality improvement tools, e.g. quarterly feedback reports/benchmarks. ∞Pharmacotherapy index: range from 0-7, one point for each medication received, ASA, clopidogrel, GB IIa/IIIb inhibitor, LMW Heparin, BB, ACE/ARB and statin.