Pepine 1999.

Methods	Study design: cross‐over trial Total study duration: 8 weeks Duration of follow‐up: no follow‐up beyond treatment phase Method of randomisation: not described Method of concealment of allocation: not mentioned Blinding: double‐blind (with "double dummy" technique) Power calculation: not mentioned Phases of the study: 2 (qualifying phase, treatment phase) Number of patients randomised: 318 Exclusions post‐randomisation: 6 (not described) Withdrawals (and reasons): premature withdrawals due to adverse events are declared to have been very similar for all treatments, but no details are provided
Participants	Total number: 312 Country of enrolment: United States, Canada. Setting/location: not specified Diagnostic criteria (stable angina pectoris): chronic (≥ 3 months) stable angina pectoris that had responded to conventional anti‐anginal therapy Comorbidities: none Age (mean, range): 64.3 (33‐85) years Gender (male %): 226 (72%) Inclusion criteria: Chronic (≥ 3 months) stable angina pectoris that had responded to conventional anti‐anginal therapy Exercise‐induced ischaemia, defined as horizontal or down‐sloping ≥1 mm ST‐segment depression persisting in 3 consecutive beats Exclusion criteria: Left ventricular hypertrophy Preexcitation Conduction abnormalities Pacemaker rhythm Unstable angina Myocardial infarction within the preceding 3 months Heart failure (New York Heart Association class III or IV) Uncorrected valvular Congenital heart disease Need for digoxin or long‐acting nitrates Labile diabetes Conditions that would confuse follow‐up evaluation
Interventions	Number of intervention groups: 4 Concomitant medications: β‐blockers and/or calcium antagonists (minimum medication needed during qualifying phase) Excluded medications: long‐acting nitrates Placebo group Intervention: placebo Duration of intervention: 1 week (5 double‐blind treatment periods in an extended period Latin square design) Ranolazine 400 mg bid group Intervention: ranolazine IR 400 mg twice daily Duration of intervention: 1 week (5 double‐blind treatment periods in an extended period Latin square design) Ranolazine 267 mg tid group Intervention: ranolazine IR 267 mg thrice daily Duration of intervention: 1 week (5 double‐blind treatment periods in an extended period Latin square design) Ranolazine 400 mg tid group Intervention: ranolazine IR 400 mg thrice daily Duration of intervention: 1 week (5 double‐blind treatment periods in an extended period Latin square design)
Outcomes	Total number of outcomes: According to study protocol: no published protocol; according to the "Methods" section: 9 (ETT time to onset of angina (peak and through), ETT duration of exercise (peak and through), ETT time to onset of ischaemic‐type ST‐segment depression (peak and through), haemodynamic, laboratory, adverse events) Reported: 9 Adverse events incidence Outcome definition: number of patients experiencing an adverse event Method and unit of measurement: percentage Time points reported: 1 week RESULTS Adverse events incidence Sample size: 312 (intention‐to‐treat) Missing participants: 6 Summary data: it is stated that adverse events rates were similar for all ranolazine and placebo regimens and approximately 25%, but data for each group is not reported. It is stated that only minor gastrointestinal complaints tended to occur more often with ranolazine (6.6% to 10.7%) than with placebo (3,2%). Subgroup analyses: not performed
Notes	Relevant observations for the data provided before: "all patients" (intention‐to‐treat) (N = 312) and per‐protocol (N = 260) analysis were performed for ETT variables Source of funding: in part by a grant from Syntex Research Notable conflicts of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation is stated but no described
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Study is declared to be double‐blinded, but no description is provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Study is declared to be double‐blinded, but no description is provided
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Exclusions and withdrawals are reported, but no reasons or explanations are provided
Selective reporting (reporting bias)	Unclear risk	There is no published protocol. Results for all the outcomes stated in the "Methods" section of the paper are reported
Other bias	Unclear risk	The study was supported in part by a grant from Syntex Research. The authors did not stated any conflicts of interest.