RITA-3RITA-3

ESC 4th September 2005

The impact of underlying risk and gender on the benefit of early intervention in non-ST

elevation acute coronary syndrome patients: findings from the RITA-3 trial

TC Clayton, SJ Pocock, RA Henderson, PA Poole-Wilson, TRD Shaw, DJ Wheatley, KAA Fox

British Heart Foundation RITA-3 Trial

RITA-3RITA-3

ESC 4th September 2005

RITA 3 Study Design

Unstable angina / non-ST-elevation MI

Intervention Conservative

PCI/CABG Angio/PCI/CABGMedical Rx

+ischemia

n=1810

n=895 n=915

Medical Rx

Angiography+72 hours

- 48 hours

Randomisation

Primary endpoints: (i) death / MI / refractory angina at 4 months(ii) death / MI at 12 months

RITA-3RITA-3

ESC 4th September 2005

Background and objectives

Outcome Intervention(n=895)

Conservative(n=915)

RR (95% CI)

Death/MI/ref angina (4m)

Death/MI (12m)

86 (9.6%)

68 (7.6%)

133 (14.5%)

76 (8.3%)

0.66(0.51- 0.85)

0.91(0.67-1.25)

Results as published:

RITA-3RITA-3

ESC 4th September 2005

Background and objectives

Intervention(n=895)

Conservative(n=915)

Interaction p-value

Men(I=545,C=583)Women(I=350,C=332)

48 (8.8%)38 (10.9%)

101 (17.3%)32 (9.6%)

0.004

Death/MI/refractory angina at 4m by gender:

Aims: To assess whether the benefits of early intervention are restricted to patients with higher underlying risk

To consider possible reasons for any gender differences in the benefits of early intervention

RITA-3RITA-3

ESC 4th September 2005

Methods

• Gender differences in patient characteristics were assessed

• A multivariate logistic regression model was developed for death/MI/refractory angina at 4 months

• Baseline risk factors were included that were significantly related to the outcome

• Patients were stratified into quartiles of underlying risk and the impact of treatment assessed

• Gender differences in outcome within each quartile were tabulated

RITA-3RITA-3

ESC 4th September 2005

Baseline characteristics

Men (n=1128)

Women (n=682)

P-value

Mean age (years) 61.8 63.3 0.002

Mean BMI (kg/m2) 27.7 28.1 0.14

Current smoker (ex-

smoker)

35% (48%) 29% (39%) <0.001

Angina CCS grade 3/4 32% 42% <0.001

Previous MI 31% 22% <0.001

Diabetes 13% 14% 0.47

Mean systolic BP (mmHg)

Mean diastolic BP (mmHg)

132

75

131

71

0.38

<0.001

Mean pulse rate (beats/min) 68 70 <0.001

Mean cholesterol (mmol/l) 5.5 5.8 <0.001

RITA-3RITA-3

ESC 4th September 2005

Risk factors of outcomeRisk factor Events/Total

(219 / 1807)Odds ratio

P-value*

Severe angina

Age (per 10 years)

Treatment Female ConsInter

Males ConsInter

ST elevation

Pulse rate (per 10 beats/min)

104 / 647

32 / 33238 / 350

101 / 58348 / 545

27 / 139

1.83

1.32

11.17

10.46

1.88

1.14

<0.001

<0.001

0.53

<0.001

0.007

0.008

* Gender/treatment interaction, p=0.003

RITA-3RITA-3

ESC 4th September 2005

Treatment effect by quartile of risk

Quartile of risk

Intervention (n=893)

Conservative (n=914)

Odds-ratio (95% CI)

First

Second

Third

Fourth

Events

Events

Events

Events

18 (7.7%)

19 (8.5%)

25 (11.3%)

24 (11.1%)

14 (6.4%)

25 (11.0%)

35 (15.2%)

59 (24.9%)

1.22 (0.59-2.52)

0.75 (0.40-1.41)

0.71 (0.41-1.24)

0.38 (0.22-0.64)

Total* Events 86 (9.6%) 133 (14.5%) 0.63 (0.47-0.83)

* Interaction between risk and treatment, p=0.003

RITA-3RITA-3

ESC 4th September 2005

Cumulative risk by quartile RITA-3RITA-3

Cu

mu

lati

ve p

erc

en

tag

e

30

25

15

10

5

0

Intervention Conservative

Time since randomisation (days)

35

20

0 30 60 90 120 180 270 365 0 30 60 90 120 180 270 365

RITA-3RITA-3

ESC 4th September 2005

Treatment effect by quartile of risk and gender

Quartile Men Women

of risk Inter (n=545)

Cons (n=583)

Inter (n=350)

Cons (n=332)

First

Second

Third

Fourth

3 / 42 (4.8%)

8 / 135 (5.9%)

17 / 162 (10.5%)

21 / 204 (10.3%)

3 / 43 (7.0%)

16 / 140 (11.4%)

27 / 148 (15.2%)

55 / 221 (24.9%)

16 / 191 (8.4%)

11 / 89 (12.4%)

8 / 59 (13.6%)

3 / 11 (27.3%)

11 / 175 (6.3%)

9 / 88 (10.2%)

8 / 53 (15.1%)

4 / 16 (25.0%)

RITA-3RITA-3

ESC 4th September 2005

Possible reasons for gender differences

• Chance - caution needed in interpretation of subgroups (low event rate seen in Conservative women)

• Gender differences seen in several important factors (but did not explain results observed)

• Women appear to be treated less aggressively (72% men with 3 VD received CABG vs 51% women)

• Women may experience more complications from invasive treatment

RITA-3RITA-3

ESC 4th September 2005

Conclusions

• Most benefit of early intervention seen in higher risk patients

• Benefit of early intervention seen in men but not in women (similar results seen for death/MI at 12 months)

• Caution needed in interpretation of results (unlikely that risk from intervention increased in women)

• Short term outcomes only assessed

• Further research is required to identify treatments to improve the prognosis of women