# Presentation: 826164

## Lumiracoxib Cardiovascular Safety

- Lourdes Villalba, MD
- DAAODP/ODE V
- February 17, 2005

## TARGET(Therapeutic COX-189 Arthritis Research and Gastrointestinal Event Trial)

- 52 weeks
- 18,000 patients with osteoarthritis
- Two sub-studies: 0117 (LUM & Naproxen)
- 				    2332 (LUM & Ibuprofen)
- 25% of patients on low dose aspirin (ASA)

-     L= lumiracoxib 400 mg; Naproxen 500 mg BID; ibuprofen 800 mg TID.
-    Note: effective dose of LUM still not defined.

## TARGET – CV Safety

- Primary CV variable: Confirmed or _probable_* APTC
- (Anti Platelet Trialist Collaboration) endpoint.
- cardiovascular / unknown cause of death
- MI (clinical or _silent_),
- stroke (hemorrhagic or ischemic)
- Other variables:  All of the above plus confirmed or probable
- cardiac arrest,
- transient ischemic attack,
- unstable angina,
- deep vein thrombosis and
- pulmonary embolism

- * As determined by Cardio and Cerebrovascular (CCV)  Safety Committee

## TARGET Confirmed & Probable APTC Events

|  | 0117 |  | 2332 |  |
| --- | --- | --- | --- | --- |
|  | LUM | Napr | LUM | Ibu |
| Randomized | 4741 | 4730 | 4376 | 4397 |
| PYR1 |   (3639)      (3534)        (3242)        (3090) |  |  |  |
| APTC | 40 |  27 | 19 | 23 |
|    CV Death | 11 |  8 |   8 | 10 |
|    NF MI2 | 16 |  9 |   5 |  5 |
|    NF Ischemic stroke
   NF Hem. stroke | 13
 0 | 11
 0 |   6
  0 |  6
 2 |

- 1PYR: patient years at risk. 2 Includes silent (ECG detected) MI  (3 and 3 in LUM and Naproxen; 0 and 2 silent MI in LUM and Ibuprofen)

## TARGET- 0117 Confirmed & Probable APTC Events

|  | LUM |  |        Napr |  |  |
| --- | --- | --- | --- | --- | --- |
|  | N= 4741 |  |       N= 4730 |  |  |
|  |    n | Rate2 | n | Rate | RR3 |
| APTC | 40 | 1.1 | 27 | 0.76 | 1.44 |
| CV Death | 11 | 0.30 | 8 | 0.23 | 1.34 |
| NF MI | 16 | 0.44 | 9 | 0.25 | 1.72 |
| NF Isch. Stroke | 13 | 0.36  | 11 |  0.31 | 1.15 |
| NF Hem. Stroke | 0 | - |  0 | - | - |

- Rate= Risk per 100 patient years. PYR (patient years at risk): LUM=  3639, naproxen= 3534

## TARGET- 0117 Confirmed & Probable APTC Events

## TARGET- 2332 Confirmed & Probable APTC Events

|  | LUM |  |        IBU |  |  |
| --- | --- | --- | --- | --- | --- |
|  | N= 4376 |  |       N= 4397 |  |  |
|  |    n | Rate2 | n | Rate | RR3 |
| APTC | 19 | 0.58 | 23 | 0.74 | 0.79 |
| CV Death | 8 | 0.25 | 10 | 0.32 | 0.76 |
| NF MI | 5 | 0.15 | 5 | 0.16 | 0.95 |
| NF Isch. Stroke | 6 | 0.19 | 6 | 0.19 | 0.95 |
| NF Hem. Stroke | 0 | - | 2 | 0.07 |  |

- 2Rate per 100 patient years. PYR (patient years at risk): LUM=  3242, Ibu=3090

## TARGET- 2332Confirmed & Probable APTC Events

##  TARGET Confirmed /Probable APTC Endpoint KM plot (%)

- Study 0117

- Study 2332

## TARGET Confirmed & Probable APTC Events

| 
 | 0017 |  | 2332 |  |
| --- | --- | --- | --- | --- |
|  |     LUM |    Nap |    LUM |     Ibu |
| Non-ASA users    N= |    3549 |   3537 |   3401 |   3431 |
| CV Death | 7 | 5 | 5 | 6 |
| NF MI | 10 | 3 | 4 | 3 |
| NF ISch. Stroke | 5 | 6 | 4 | 2 |
| ASA users          N= |     1192 |    1193 |     975 |     966 |
| CV Death | 4 | 3 | 3 | 4 |
| Non-fatal MI | 6 | 6 | 1 | 2 |
| Non-fatal stroke | 8 | 5 | 2 | 4 |

## TARGET Confirmed & Probable MI Events

## TARGET - conclusions

- No definitive conclusions regarding COX-2 selective class effect
- LUM higher CV risk vs. naproxen (0117)
- LUM similar CV risk vs. ibuprofen (2332)
- LUM seems to behave differently in studies 0117 and 2332.
- Exposure “only” one year
- OA population (not as high CV risk as others)
- Unclear how low dose ASA will affect RR
- Unclear role of BP
- No data vs. placebo