Question 12- Paragon Trial

Question 1

Study Characteristics

Answer 1

• paragon was designed to evaluate the efficacy & safety of sacubitril valsartan vs. valsartan in patients w/chronic HFpEF 45% and above.
• study went from July 2014-April 2019

Question 2

Primary & Secondary End Points

Answer 2

Primary- a composite of total (first and recurrent) hospitalizations for HF and death from CV causes.

Secondary- considered exploratory b/c primary end point analysis didn’t meet the predetermined level of statistical significance.

Question 3

Inclusion Criteria

Answer 3

• Patients 50 and older w/signs and symptoms of HF
• NYHA class 2-4
• evidence of structural heart disease less than 6 months prior to enrollment
• elevated Nt-proBNP levels
• Diuretic therapy 30 days or less prior to screening

Question 4

Exclusion Criteria

Answer 4

• any prior LVEF <40%
• acute coronary syndrome, cardiac/CV surgery or intervention 3 months or less.
• required 2 or more of an ACE, ARB, or renin inhibitor
• severe pulmonary disease
• obesity
• anemia
• uncontrolled hypertension

Question 5

Study Design

Answer 5

• multicenter, randomized, double-blind trial
• patients had to discontinue ACE or ARB therapy
• There were single-blind run-in periods where they received 80mg of valsartan twice daily for 1-2 weeks.
• any patient successful in completing the run-in period, were randomized to receive either 200mg of Entresro twice daily or 160mg of valsartan.

Question 6

Patient Characteristics

Answer 6

• studied 4,796 patients with HFpEF of 45% + and structural heart disease
• the mean age for patients was 73 yrs old w/52% being females.
• 81% were white, 13% asian, 2% black
• studied NYHA Class 2-4, w/ 77% patients falling in Class 2
• mean ejection fraction was 57%

Question 7

Safety

Answer 7

Adverse Events

• hypotension
• elevated potassium levels
• angioedema
• elevated serum creatinine

Question 8

Efficacy

Answer 8

entresto showed a 12.8% reduction in the total # of HF hospitalizations and CV deaths vs. valsartan alone which showed a 14.6% reduction

Question 9

Benefits

Answer 9

There were no significant findings between sacubitril valsartan vs valsartan. However, Paragon did show the reduction of hf related hospitalizations and death.