Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)

Prior treatment

• Use of anti-retroviral protease inhibitors (e.g. ombitasvir, paritaprevir, ritonavir, dasabuvir) or topiramate.
• Participants considered by the investigator to be unsuitable for the study for any of the following reasons: Not agreeable for treatment with metformin or anticipated to have poor compliance on study drug treatment; inability to follow diet or exercise instructions; unwilling to attend study follow-up visits
• Life expectancy less than 2 years due to concomitant disease.
• Use of anti-retroviral protease inhibitors (e.g. ombitasvir, paritaprevir, ritonavir, dasabuvir) or topiramate.
• Participants considered by the investigator to be unsuitable for the study for any of the following reasons: Not agreeable for treatment with metformin or anticipated to have poor compliance on study drug treatment; inability to follow diet or exercise instructions; unwilling to attend study follow-up visits
• Life expectancy less than 2 years due to concomitant disease.

Other illness

• NYHA Functional Class IV heart failure
• On metformin or other pharmacologic therapy for diabetes mellitus.
• Planned antiarrhythmic (class I or III) drug change, AF ablation/PVI procedure or cardiac surgery over the first 3 mos of the study
• History of AF.
• NYHA Functional Class IV heart failure
• On metformin or other pharmacologic therapy for diabetes mellitus.
• Planned antiarrhythmic (class I or III) drug change, cardiac surgery over the first 3 mos of the study

Lab values

• Moderate renal disease (eGFR \<45 ml/min/1.73 m2)
• Hepatic dysfunction - bilirubin \>1.5x ULN, unless due to Gilbert's syndrome
• For patients on dofetilide with a pacemaker, QTc \>490 ms if QRS duration is \</=100 ms. If QRS duration is \>100 ms, adjusted QTc \>490 ms. Adjusted QTc = QTc - (QRS duration - 100 ms).
• Moderate renal disease (eGFR \<45 ml/min/1.73 m2)
• Hepatic dysfunction - bilirubin \>1.5x ULN, unless due to Gilbert's syndrome
• For patients on dofetilide with a pacemaker, QTc \>490 ms if QRS duration is \</=100 ms. If QRS duration is \>100 ms, adjusted QTc \>490 ms. Adjusted QTc = QTc - (QRS duration - 100 ms).

Age

• Age \<18 years old.
  • TRIM - No AF Cohort
• Age \<18 years old.

Other

• Permanent AF with no plans to convert to sinus rhythm.
• If in persistent AF, current episode \>12 months in duration (current long-standing persistent AF)
• Known sensitivity to metformin
• Significant alcohol use (average \>2 drinks/day)
• AF ablation/PVI procedure performed in the past 6 months
• Device changed or implanted in the past 3 months
• Women who are pregnant, breast-feeding or of child-bearing potential and not willing or able to use an acceptable form of contraception.
• Significant alcohol use (average \>2 drinks/day)
• Device changed or implanted in the past 3 months
• Women who are pregnant, breast-feeding or of child-bearing potential and not willing or able to use an acceptable form of contraception.

• Permanent pacemaker or implantable cardioverter-defibrillator (ICD) (with or without cardiac resynchronization therapy (CRT) with an implanted atrial lead capable of providing AF diagnostics and remote monitoring.
• Paroxysmal AF, or persistent AF with plans for conversion.
• AF on cardiac implantable electrical device (CIED) over the past 3 months with at least 1 episode lasting ≥5 minutes.
• If on an antiarrhythmic drug, then on a stable regimen for the past 3 months.
• Permanent pacemaker or ICD (with or without CRT) with an implanted atrial lead capable of providing AF diagnostics and remote monitoring.
• No AF on CIED over the past 6 months.
• No history of AF.
• Age \>/=18 years old.

Criteria the registry did not label

• TRIM-AF Cohorts