Mitral regurgitation (MR) is common in the elderly and its prevalence is increasing with the
aging of the population. Organic MR, due to primary valvular lesions, initiates a cascade of
complications determined by its degree. MR of severe degree is associated with excess
mortality and high cardiac morbidity (heart failure, atrial fibrillation). It also causes
left ventricular remodeling which induces left ventricular dysfunction, which in turn leads
to poor clinical outcome. Surgery can eliminate MR, but carries immediate and long-term
risks, especially in the elderly. Therefore, chronically decreasing the degree of MR is a
major goal of medical therapy but such an effect is yet unproved because of conflicting
results of small and mostly non-randomized series. Our recent preliminary studies suggest
that a sustained decrease of degree of MR and improvement of left ventricular remodeling can
be achieved with powerful reduction of afterload, obtained in particular with angiotensin-II
receptor blockade. Therefore, the present proposal seeks to address gaps of knowledge
regarding vasoactive treatment of MR through the verification of the following hypothesis:
Hypothesis: Vasoactive therapy using angiotensin-II receptor blocker (Candesartan Cilexetil)
weighed against placebo produces a sustained reduction of the consequences of organic MR. The
specific aims are that the treatment a) decreases the degree of MR (decreases the regurgitant
volume, primary end-point) and b) improves left ventricular remodeling (decreases the
end-diastolic volume index, secondary end-point), as compared to placebo.
Phase:
Phase 4
Details
Lead Sponsor:
Mayo Clinic
Treatments:
Angiotensin II Angiotensinogen Candesartan Candesartan cilexetil