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Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate.

circulation journal

Randomized Study of Angiotensin II Type 1 Receptor Blocker vs Dihydropiridine Calcium Antagonist for the Treatment of Paroxysmal Atrial Fibrillation in Patients With Hypertension The J-RHYTHM II Study Design for the Investigation of Upstream Therapy for Atrial Fibrillation