FRISC‐II.

Methods	Prospective, randomised, multicentre trial with parallel groups. Invasve and non‐invasive treatments compared by factorial design.
Participants	2457 participants with anginal pain within the last 48 hours and ST depression or elevated cardiac markers. Overall impression of participant risk level: intermediate‐high.
Interventions	Conservative arm: aspirin, beta blocker, statin, ACEI, dalteparin or UFH. Invasive arm: as above and routine angiography (average time to angiography: 4 days). 10% glycoprotein 2b/3a receptor antagonist use. Each strategy further randomised to placebo or dalteparin in a double‐blind fashion.
Outcomes	Death all causes (6, 12, 24 months, 5 years), MI (6, 12, 24 months, 5 years), refractory angina (6 months), death or non‐fatal MI (6, 12, 24 months, 5 years), rehospitalisation (6 weeks, 6, 12 months), procedural MI, bleeding, contrast allergy.
Notes	Sponsored by Pharmacia and Upjohn (a subsidiary of Pfizer).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random sequence generation algorithm was not disclosed. An independent organisation performed randomisation. There were no significant differences in baseline characteristics of the groups, which supports minimal selection bias.
Allocation concealment (selection bias)	Low risk	An independent organisation performed randomisation by telefax (Clinical Data Care, Lund, Sweden).
Blinding (performance bias and detection bias) All outcomes	High risk	Allocation to invasive and non‐invasive strategies was open (allocation to long‐term dalteparin treatment with placebo was double‐blinded).
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition was equivalent between groups. The trial randomised 1222 participants to invasive, with 32 lost to 6‐month follow‐up (2.62%) compared with 1235 participants randomised to conservative management and 49 lost to 6‐month follow‐up (3.96%). The trial used intention‐to‐treat (ITT) analysis.
Other bias	Low risk	The sponsoring pharmaceutical company employed continuous source‐data verification of all case‐record forms by external monitors. An independent clinical‐event committee and a data and safety monitoring board adjudicated adverse events.