Biomarker Guided Therapies in Stage A/B Heart Failure
Condition: Hypertension; Diabetes; Cardiovascular Disease
MeSH terms: Heart Failure; Cardiovascular Diseases
Intervention: Carvedilol; Spironolactone; Usual care
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: heart failure; biomarkers; troponin; BNP; carvedilol; spironolactone; prevention

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.
    

Eligibility criteria:

        Inclusion Criteria:

        Only Veterans are eligible to participate. Other inclusion criteria include

          -  Age greater than 40 years

          -  One of the following in order to establish Stage A HF a. Hypertension b. Diabetes
             mellitus (controlled: defined as hemoglobin A1c less than 9%) c. Obesity (defined as
             BMI greater than 30 kg/m2) d. Metabolic syndrome (using the National Cholesterol
             Education Panel definition) e. Left ventricular hypertrophy (by ECG) f. Coronary or
             cerebrovascular arterial disease

          -  Troponin T measured by the high sensitivity assay of greater than 5ng/L

          -  Systolic BP 120-155 mmHg at primary care provider (PCP) visit and prerandomization
             visit (i.e., 2 separate confirmations of the same). If there is discordance between
             the PCP visit and pre-randomization the investigators will bring patient back to
             recheck his BP and use that as the tie breaker. Not orthostatic with measurements
             (defined as a fall in systolic BP greater than 20 mmHg when subjects assume an upright
             position). - Estimated 10-yr HF risk (based on Atherosclerosis Risk in Communities HF
             Lab model) greater than 5%

          -  Provides informed consent

        Exclusion Criteria:

        The exclusion criteria include

          -  Active Atrial fibrillation

          -  History of chest/ neck radiation

          -  High-risk chronic obstructive pulmonary disease (COPD) (GOLD classification 3-4 with
             greater than equal to 2 COPD exacerbations in the last 12 months)

          -  Known allergy to carvedilol or spironolactone

          -  Renal insufficiency with estimated Glomerular Filtration Rate (eGFR) less than 60
             ml/min

          -  Serum potassium greater than 5 meq/L

          -  Current use of carvedilol, spironolactone, any other beta-blockers or aldosterone
             antagonists

          -  Signs of clinical HF on initial examination (pulmonary rales/crackles, elevated
             jugular venous pulse with S3/S4 on auscultation)

          -  Left ventricular ejection fraction <50% by echo

          -  Moderate or greater valve stenosis or regurgitation

          -  Hypertrophic cardiomyopathy

          -  Exposure to known cardiotoxic chemotherapy

          -  Poor echo image quality

          -  Right ventricular dysfunction more than mild

          -  Any valvular dysfunction that is more than mild

          -  Any life-threatening disease expected to result in death within the next 2 years

          -  Active severe liver disease (evaluated at Visit 1): cirrhosis, active hepatitis,
             aspartate transaminase (ALT) or alanine transaminase (AST) greater than 3 x ULN, or
             biliary obstruction with hyperbilirubinemia (total bilirubin greater than 2 x ULN).

          -  Participation in another clinical trial involving an investigational agent within 90
             days prior to randomization

          -  Any condition or therapy which, in the opinion of the investigator, might pose a risk
             to the patient or make participation in the study not in the patient s best interest

          -  Drug or alcohol abuse within the past 6 months, and unable/unwilling to abstain from
             drug abuse and excessive alcohol consumption during the study. Excessive alcohol
             consumption is on average greater than 2 units of alcohol per day. A unit of alcohol
             is defined as a 12-ounce (350 mL) beer, 5-ounce (150 mL) wine, or 1.5-ounce (45 mL) of
             80 ]proof alcohol for drinks.

          -  Mental/psychological impairment or any other reason to expect patient difficulty in
             complying with the requirements of the study.

          -  Any immunosuppressed condition where intercurrent illnesses may affect interpretation
             of study results

          -  Pregnant women or any woman planning a pregnancy during the study period

          -  Not meeting any of the inclusion criteria