Biomarker Guided Therapies in Stage A/B Heart Failure
Condition: Hypertension; Diabetes; Cardiovascular Disease
MeSH terms: Heart Failure; Cardiovascular Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      Despite advances in cardiovascular care, the occurrence of heart failure (HF) is steadily
      increasing. The increase in HF rates poses enormous challenges, as once an individual becomes
      symptomatic or requires hospitalization with HF, the prognosis remains poor. Therefore,
      prevention of HF is essential. HF prevention is a critical issue as HF risk factors that
      include common medical conditions such as hypertension and diabetes are also increasing.
      However, not everyone with these risk factors develops HF. Using novel blood tests, the
      investigators propose to identify and treat subjects at higher HF risk to see if the
      investigators can stabilize or improve ultrasound measures known to be associated with HF
      risk. This study will enroll only Veterans.
    

Detailed description: 
      Recently the investigators have shown that HF risk prediction can be improved using cardiac
      troponin T measured with a novel high-sensitivity assay (hs-cTnT) and N-terminal pro-B-type
      natriuretic peptide (NT-proBNP). Furthermore, hs-cTnT seems to identify individuals at higher
      risk among those with established risk factors (such as hypertension) for HF. In preliminary
      results, the investigators have shown that individuals with systolic blood pressure of
      120-129 mm Hg and elevated hs-cTnT have a higher rate of incident HF than those with systolic
      blood pressure of 140-159 mm Hg and undetectable hs-cTnT. Therefore, the investigators
      believe that by using hs-cTnT to estimate HF risk the investigators can identify individuals
      in whom aggressive modification of risk factors such as high blood pressure will be
      associated with a favorable risk-benefit ratio.

      The investigators' objective/specific aim therefore is to evaluate if treatment of selected
      subjects with Stage A or B HF (i.e., those with hs-cTnT >5 ng/L and an estimated 10-year HF
      hospitalization risk of >5%) who have reasonably well-controlled blood pressure with
      antihypertensive agents (carvedilol or spironolactone) will be associated with improvement of
      surrogate markers associated with incident HF (i.e., speckle-tracked cardiac and vascular
      strain). Carvedilol and spironolactone were chosen for the following reasons: a) they are not
      routinely used as first-line antihypertensive agents; b) beta-blockade was associated with
      decreases in hs-cTnT in the preliminary analysis of subjects with established HF; and c) the
      mechanism of actions of carvedilol and spironolactone provide a sound scientific rationale
      for use in prevention of HF.

      Using a prospective open-label blinded end point (PROBE) design, the investigators propose to
      randomize 210 subjects aged >40 years with systolic blood pressure between 120-155 mm Hg,
      cardiac troponin T (measured with a novel high-sensitivity assay) level >5 ng/L, and 10-year
      HF risk >5% (estimated using a validated laboratory model including demographic factors,
      NT-proBNP, and hs-cTnT) to receive carvedilol (nonselective beta-blocker), spironolactone
      (aldosterone antagonist), or usual care for 18 months. The primary end point will be change
      in global longitudinal systolic myocardial strain estimated using 2D speckle tracking.
      Additionally, changes in vascular strain and biomarkers will be evaluated. This study will
      help us identify whether both or either of the medications can be further tested in large
      randomized clinical trials to prevent the incidence of HF.
    

Intervention name(s): Carvedilol; Spironolactone; Usual care
Intervention type(s): Drug; Drug; Other
Intervention description(s): Carvedilol is a non selective beta blocker; Spironolactone is an aldosterone antagonist and can lower blood pressure/ is used in heart failure; standard care as per primary care provider
Intervention MeSH terms: Carvedilol; Spironolactone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: heart failure; biomarkers; troponin; BNP; carvedilol; spironolactone; prevention