# Presentation: 687536

## Time to First CHF Hospitalization for All PatientsV-HeFT I, V-HeFT II

**V-HeFT I**

**V-HeFT II**

**Patients, n**
**ISDN/HYD****	****186****	****138****	****94****	****401****	****316****	****223**
**Placebo****	****273****	****173****	****112****	**
**Enalapril****	****	****	****	****403****	****321****	****236**

**Time, days since randomization**

**ISDN/HYD****Placebo**

**ISDN/HYD****Enalapril**

**60**

**70**

**80**

**90**

**100**

**0**

**365**

**730**

**60**

**70**

**80**

**90**

**100**

**0**

**365**

**730**

**Without hospitalization, %**

**DV**

## Time to First CHF Hospitalization for Black Patients and White PatientsV-HeFT I

**26**

- DV Final NDA20-727_Brief_Document.pdf F 6

**Patients, n**
**ISDN/HYD****	****49****	****41****	****30****	****132****	****94****	****62**
**Placebo****	****79****	****50****	****36****	****192****	****122****	****76****	**

**Time, days since randomization**

**ISDN/HYD****Placebo**

**Black patients**

**40**

**50**

**60**

**70**

**80**

**90**

**100**

**0**

**365**

**730**

**Percent without HF hospitalization**

**White patients**

**40**

**60**

**80**

**100**

**0**

**365**

**730**

## Time to First CHF Hospitalization for Black Patients and White PatientsV-HeFT II

**26**

**Patients, n**
**ISDN/HYD****	****109****	****88****	****60****	****282****	****220****	****159**
**Enalapril****	****106****	****82****	****60****	****292****	****236****	****175****	**

**Time, days since randomization**

**40**

**50**

**60**

**70**

**80**

**90**

**100**

**0**

**365**

**730**

**Without HF hospitalization, %**

**Black patients**

**White patients**

**ISDN/HYD****Enalapril**

## Patients With Unscheduled Emergency Room VisitsA-HeFT

|  |  | Patients, % |  |  |
| --- | --- | --- | --- | --- |
|  | Unscheduled visits | BiDil®n = 518 | Placebon = 532 | P value |
| Any reason | 0 | 73.2 | 72.4 | 0.782 |
|  | 1 | 17.0 | 16.4 |  |
|  | 2 | 5.2 | 5.5 |  |
|  | 3 | 1.9 | 3.2 |  |
|  | ≥ 4 | 2.7 | 2.3 |  |
| HF | 0 | 96.5 | 94.4 | 0.105 |
|  | 1 | 2.7 | 4.5 |  |
|  | 2 | 0.6 | 0.4 |  |
|  | 3 | 0.2 | 0.8 |  |
| Cardiac cause | 0 | 93.8 | 94.9 | 0.503 |
|  | 1 | 5.2 | 4.5 |  |
|  | 2 | 0.6 | 0.4 |  |
|  | 3 | 0.4 | 0.2 |  |
| Non-cardiac cause | 0 | 77.4 | 78.2 | 0.767 |
|  | 1 | 15.4 | 14.5 |  |
|  | 2 | 4.4 | 3.9 |  |
|  | 3 | 1.4 | 1.1 |  |
|  | ≥ 4 | 1.4 | 2.3 |  |

- DV A-HeFT CSR T38

- 16

## Slide 5

## Percent of Patients With QoL Data at Each VisitA-HeFT

|  | BiDil® |  | Placebo |  |
| --- | --- | --- | --- | --- |
| Timepoint | N | n (%) | N | n (%) |
| Baseline | 518 | 512 (99) | 532 | 528 (99) |
| Mo 3 | 438 | 423 (97) | 471 | 441 (94) |
| Mo 6 | 388 | 369 (95) | 382 | 371 (97) |
| Mo 9 | 319 | 307 (96) | 315 | 305 (97) |
| Mo 12 | 278 | 269 (97) | 264 | 250 (95) |
| Mo 15 | 226 | 226 (100) | 218 | 218 (100) |
| Mo 18 | 198 | 198 (100) | 184 | 184 (100) |

- DV A-HeFT final rpt, pub 1.19

## MLHF Questionnaire─Change in Score at 6 mo and at Endpoint Using LOCFA-HeFT

| Change in score at 6 mo in all patients |  |  |  |
| --- | --- | --- | --- |
|  | BiDil® | Placebo | P value† |
| N | 369 | 371 | 0.0105 |
| Mean | –7.1 | –3.1 |  |
| SD | 20.61 | 21.27 |  |
| Change in score at endpoint using LOCF |  |  |  |
| N | 512 | 528 | 0.0030 |
| Mean | –7.6 | –3.4 |  |
| SD | 22.57 | 22.74 |  |

**† ****2-sample *****t *****test.**

- A-HeFT final rpt, T16.1

## Sensitivity Analyses Results for Primary Endpoint A-HeFT

- DV A-HeFT CSR T27

- 16

|  | BiDil® | Placebo | P value |
| --- | --- | --- | --- |
| No HF hospitalization imputation [1] |  |  |  |
| 	N | 518 | 532 | 0.014 |
| 	Mean ± SD | –0.14 ± 1.91 | –0.45 ± 2.03 |  |
| 	Range | –6 to 2 | –6 to 2 |  |
| Last known QOL [2] |  |  |  |
| 	N | 518 | 532 | 0.005 |
| 	Mean ± SD | 0.03 ± 1.79 | –0.36 ± 2.03 |  |
| 	Range | –6 to 2 | –6 to 2 |  |
| Patients randomized on or prior to April 19, 2004 [3] |  |  |  |
| 	N | 475 | 477 | 0.015 |
| 	Mean ± SD | –0.18 ± 1.95 | –0.52 ± 2.07 |  |
| 	Range | –6 to 2 | –6 to 2 |  |

**Primary analysis population using last known QoL assessment ****≤ 6 months; last known HF hospitalization and survival; no imputation for missing HF hospitalization or survival.**
**Primary analysis population using last known QoL assessment during the trial, with imputation of worst score for QoL for those patients without any QoL post-baseline; HF hospitalization and survival imputation using Worst-Case scenario.**
**Patients with the opportunity to have at least 3 months of follow-up and, therefore, a 3-month QoL assessment, with imputation of worst score for QoL for those patients without any 3-month QoL; HF hospitalization and survival imputation using Worst-Case scenario.**

## AE Incidence by Race—Black Patients and White PatientsV-HeFT I, V-HeFT II

|  | Patients, % |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- |
|  | Black |  |  | White |  |  |
|  | ISDN/HYDn = 158 | Placebon = 79 | Enalapriln = 106 | ISDN/HYDn = 414 | Placebon = 192 | Enalapriln = 292 |
| Headache | 72 | 54 | 64 | 78 | 49 | 59 |
| Dizziness | 67 | 53 | 67 | 68 | 63 | 67 |
| Arthralgias | 65 | 61 | 72 | 67 | 57 | 72 |
| Other | 52 | 44 | 59 | 65 | 52 | 68 |
| Palpitation | 53 | 37 | 49 | 58 | 47 | 56 |
| Nausea or vomiting | 47 | 41 | 57 | 55 | 47 | 60 |
| Ischemic chest pain | 37 | 37 | 42 | 49 | 44 | 48 |
| Diarrhea | 40 | 38 | 43 | 43 | 39 | 45 |
| Flushing | 32 | 28 | 22 | 38 | 31 | 36 |
| Rash | 32 | 29 | 35 | 42 | 42 | 41 |
| Fever | 33 | 22 | 29 | 35 | 28 | 33 |
| Syncope | 23 | 20 | 15 | 18 | 26 | 12 |

-  DV ISS-T14, 15

**27**

## Arthritis-Related AEs in Safety Population

|  | Patients, n (%) |  |
| --- | --- | --- |
|  | BiDil®n = 517 | Placebon = 527 |
| Arthralgia | 8 (1.5) | 2 (0.4) |
| Arthritis | 8 (1.5) | 7 (1.3) |
| Arthritis rheum | 1 (0.2) | 1 (0.2) |
| Arthrosis | 1 (0.2) | 3 (0.6) |
| Joint disorder | 6 (1.2) | 7 (1.3) |
| Synovitis | 0 | 1 (0.2) |

**6**

- DV A-HeFT CSR T56