Aliskiren and Renin Inhibition in Diastolic Heart Failure (ARID-HF)

• Compare the baseline level of RAAS dysregulation between Mexican Americans and non-Hispanic whites with stable diastolic HF by measuring established biomarkers. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Evaluate the superiority of aliskiren plus spironolactone combination over an lisinopril plus spironolactone combination in inhibiting the RAAS system among patients with diastolic HF. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Compare the clinical and biological benefit of RAAS system inhibition between aliskiren plus spironolactone and lisinopril plus spironolactone as measured by clinical indicators and serum biomarkers [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Assess ethnicity-specific differences in the clinical response to either RAAS inhibition treatment between Mexican Americans and non-Hispanic whites. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

This study is being conducted to compare the effects that 2 different combinations of heart failure medications have on the levels of certain blood markers which cause and/or worsen heart failure. Additionally, the investigators will investigate any differences that may exist between Hispanics and Non-Hispanics. The investigators hope to find that Hispanic Americans will have a greater response to this new regimen compared to non-Hispanic Americans.

Our main hypothesis is that in contrast to non Hispanic whites, the degree of RAAS system activation is more pronounced in Mexican Americans with diastolic HF and consequently their response to RAAS inhibition therapy is greater. Blocking the RAAS with renin inhibitor plus aldosterone receptor blocker should produce measurable changes in biomarkers as well as physiologic improvement that could therefore translate into improved clinical outcomes. These changes should be greater appreciated in Mexican Americans if the central pathophysiologic influence of HF in this population was RAAS maladaptation.

• No Intervention: Nationality
  Hispanic versus Non-Hispanic (white) Americans
  Intervention: Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone
• Active Comparator: Drug
  Aliskiren plus spironolactone vs. Lisinopril plus spironolactone
  Intervention: Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone

Inclusion Criteria:

1. Chronic stable diastolic HF documented by clinical diagnosis and echocardiogram within the last 2 years
2. NYHA classes I-III, symptomatically stable (for >1month)
3. Age 21-70 years
4. Either of Hispanic ethnicity (Mexican American origin) or non-Hispanic white
5. Patients on ACE inhibitor therapy (lisinopril)
6. Blood pressure >100/75 mmHg
7. Adequate birth control
8. Patients seen in TTUHSC Cardiology or Internal Medicine clinic for at least two visits since January 2008

Exclusion Criteria:

1. Acute coronary syndrome (within the last month).
2. Recent acute diastolic or systolic HF (within the last month)
3. Pancreatic disease
4. Renal artery stenosis
5. Pregnancy
6. History of angioedema
7. Severe hypotension (systolic BP<90mmHg or mean arterial pressure <65mmHg)
8. Hyperkalemia (defined by K+>5 mEq/L)
9. Chronic Kidney Disease (Stage 3 and above)
10. Systolic dysfunction (ejection fraction below 50%)
11. Ethnicity other than Mexican American or non-Hispanic white