Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Atrial fibrillation (AF) is a serious public health problem because of its increasing
 incidence and prevalence in the aging population. AF is associated with elevated risks of
 death, stroke, coronary event, heart failure, cognitive decline, and chronic kidney disease.
 To identify preventive interventions for major cardiovascular events beyond effective
 anticoagulation should be a major priority in the treatment of AF patients. The CRAFT study
 is a 2-arm, multicenter, randomized clinical trial designed to test whether intensive blood
 pressure control will reduce the risk of major cardiovascular events in AF patients.
The CRAFT trial will include approximately 6000 AF patients with home SBP 125-154 mmHg and at
 least another cardiovascular risk factor. The trial aims to compare the effects of
 randomization to a treatment program of an intensive SBP goal (target home SBP <120mmHg) with
 randomization to a treatment program of a standard goal (target home SBP <135mmHg). The
 primary hypothesis is that cardiovascular event rates will be lower in the intensive arm.
 Participants will be recruited over a 3-year period at approximately 100 to 150 clinical
 centres and the first patient will be followed for up to 5 years.
Screening and Run-in Assessment

 All patients with documented AF (paroxysmal, persistent) and standard office SBP 140-179
 mmHg if not on BP-lowering drugs or 125-164 mmHg with BP-lowering drugs, will be screened
 for inclusion into the run-in assessment phase.

 The run-in assessment is for 2 weeks. In the run-in phase, patients should be treated
 according to guideline recommendation, with combined antihypertension agents. Patients
 should also be guided to measure and upload HBPM measurements correctly. BP measurements (3
 readings in the morning and 3 readings in the evening) are required to be uploaded every
 day for a week before the end of run-in assessment. Patients with average home SBP 125-154
 mmHg during the run-in assessment are considered eligible for study inclusion. If home SBP
 ≥155 mmHg or <125 mmHg at the time of run-in assessment, another 2 weeks run-in phase can
 be extended, during which time antihypertensive drugs can be titrated according to the BP
 lowering algorithm used in this study.

 Inclusion Criteria

 1. Adults, ≥18 years old

 2. Documented AF: persistent atrial fibrillation or at least two episodes of intermittent
 atrial fibrillation in the previous 6 months.

 3. Home SBP 125-154 mmHg, defined as average of all SBP readings (at least 3 readings 1
 min apart in the morning before taking antihypertensive drugs and evening before going
 to sleep) during the run-in assessment.

 4. One or more cardiovascular risk factors: (1) Prior history of thromboembolism: defined
 as any of the following criteria: a) ischemic stroke; b) transient ischemic attack
 (TIA); c) systemic embolism (SE); (2) Diabetes mellitus (DM): defined as any of the
 following criteria: a) use of oral hypoglycemic drugs or insulin; b) random blood
 glucose values ≥11.1 mmol/L in the presence of classic symptoms of hyperglycemia; c)
 fasting plasma glucose values ≥7.0 mmol/L; d) two-hour plasma glucose values ≥11.1
 mmol/L during an oral glucose tolerance test; e) HbA1C values ≥6.5%; (3) Coronary
 artery disease or Peripheral artery disease: defined as any of the following criteria:
 a) Previous myocardial infarction (MI), percutaneous coronary intervention (PCI),
 coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting;
 b) Peripheral artery disease (PAD) with revascularization; c) Acute coronary syndrome
 with or without resting ECG change, ECG changes on a graded exercise test, or positive
 cardiac imaging study; d) At least a 50% diameter stenosis of a coronary, carotid, or
 lower extremity artery; e) Abdominal aortic aneurysm ≥5 cm with or without repair; (4)
 Chronic kidney disease (CKD): defined as estimated glomerular filtration rate (eGFR)
 30-59ml/min/1.73m2 based on the latest lab value within the past 6 months; (5) Age ≥65
 years old

 Exclusion Criteria

 1. Prior AF catheter or surgical ablation, or percutaneous left atrial appendage
 occlusion

 2. Moderate-to-severe mitral stenosis, or mechanical heart valve replacement

 3. Home SBP ≥145 mmHg while already taking ≥4 full dose BP lowering agents, indicating
 resistant hypertension or poor adherence.

 4. Unable to upload home BP readings for at least 5 days during the run-in assessment.

 5. An indication for a specific BP lowering medication (e.g., beta-blocker following
 acute myocardial infarction) that the person is not taking, without evidence of
 intolerance. The screenee should be on the appropriate dose of such medication before
 assessing whether he/she meets the CRAFT inclusion criteria.

 6. Known secondary cause of hypertension that causes concern regarding safety of the
 protocol.

 7. One minute standing SBP < 110 mm Hg. Not applicable if unable to stand due to
 wheelchair use.

 8. Diagnosis of polycystic kidney disease

 9. Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy

 10. eGFR <30 mL/min/1.73m2 or end-stage renal disease (ESRD)

 11. Cardiovascular event or procedure (as defined above as Coronary artery disease or
 Peripheral artery disease for study entry) or hospitalization for unstable angina
 within last 3 months

 12. Heart failure with reduced left ventricular ejection fraction (< 40%), or New York
 Heart Association Class III-IV

 13. Individuals who have been previously diagnosed with dementia by their physicians

 14. A medical condition likely to limit survival to less than 3 years, or a cancer
 diagnosed and treated within the past two years that, in the judgment of clinical
 study staff, would compromise a participant's ability to comply with the protocol and
 complete the trial.

 15. Any factors judged by the investigator to be likely to limit adherence to
 interventions. For example, active alcohol or substance abuse, significant memory or
 behavioural disorder.

 16. Currently participating in another clinical trial (intervention study). Note: Patient
 must wait until the completion of his/her activities or the completion of the other
 trial before being screened for CRAFT.

 17. Living in the same household as an already randomized CRAFT participant

 18. Any organ transplant

 19. Unintentional weight loss > 10% in last 6 months

 20. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not
 using birth control