Overview

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.

Eligibility

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. Successful AF ablation (no documented recurrence of AF, atrial flutter, or atrial
             tachycardia lasting >30s)
          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