6/5/2006 - 1 1 cardiovascular disease outcomes in hypertensive patients stratified by baseline...

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CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION

RATE (4 GROUPS by GFR)

ALLHAT

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Introduction• Over 13 million Americans are estimated to have

chronic kidney disease (CKD)• Patients with CKD are at very high risk for

cardiovascular disease (CVD)• There are limited data about the comparative

effects of antihypertensive therapy on CVD outcomes in CKD patients

• Since risk of CVD is much higher than risk for ESRD in CKD patients, choices of therapy need to be guided by effects on CVD outcomes

• 17.7% (n=7116) of ALLHAT participants had an estimated GFR <60 ml/min/1.73m2 at baseline

ALLHAT

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Other Studies

• Many trials that studied patients with CKD do not have adequate assessment / reporting or power to evaluate CV events– HOPE demonstrated increased CV risk in patients

with renal insufficiency and that ramipril reduced risk in this subgroup compared to placebo

– IDNT and RENAAL showed similar CV event rates with ARB vs CCB (IDNT) and placebo (RENAAL), except hospitalization for first heart failure in RENAAL was lower with the ARB

– AASK (beta blocker, ACE, CCB) showed no difference in CV event rates

ALLHAT

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Normal GFR (90)

Mild GFR (60-

89)

Moderate GFR (30-

59)Severe

GFR (<30)N 8,126 18,109 5,480 182Mean age, y 63.3 67.3** 70.7** 70.3**Black non-Hisp, % 43.1 27.7** 24.9** 42.9Women, % 46.6 44.5** 52.1** 58.8**Mean SBP 145.9 146.3 146.6** 150.0**Mean DBP 84.9 82.5** 84.1** 83.7Type 2 diabetes, % 45.2 32.8** 33.1** 41.8History of CHD***, % 21.2 26.3** 30.6** 28.0**

Baseline Characteristics Stratified By Estimated GFR*

*Estimated (eGFR) (ml/min/1.73 m2) calculated by simplified MDRD equation (Levey et al., J Am Soc Nephrol 11, A 0828. 2000.)** p<.05 compared with normal GFR***p<0.022, amlodipine (28%) vs. chlorthalidone (31%) in participants with GFR 30-59.

ALLHAT

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1.00 1.081.33

2.21

-0.10

0.40

0.90

1.40

1.90

2.40

GFR90+ GFR60-89 GFR30-59 GFR<30

RelativeRisk forincidentCVD

Estimated (eGFR) (ml/min/1.73 m2) calculated by simplified MDRD equation

* P <0.001 vs. GFR90+

ALLHAT

*

Relative Risk of Combined CVD by Baseline GFR Group

(Adjusted for age, race, gender, BMI, SBP, DBP, HDL-cholesterol, LDL-cholesterol, fasting triglycerides, history of

diabetes, and cigarette smoking)

**

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Blood Pressure at 4 Years by Treatment Group and Baseline GFR

GFR Chlor Amlod Lisin

SBP -mean (sd,N)

90 133.4 (15.2, 2276) 134.6 (14.4, 1462)* 135.6 (17.3, 1301)*

60-89 133.6 (15.5, 5310) 134.5 (14.6, 3127)* 135.2 (16.9, 3024)*

30-59 135.6 (17.2, 1488) 135.9 (17.0, 855) 136.4 (18.3, 797)

<30 130.9 (14.8, 23) 133.5 (18.2, 14) 137.4 (15.9, 16)

DBP -mean (sd,N)

90 76.8 (9.5, 2276) 76.4 (9.0, 1462) 77.6 (10.1, 1301)*

60-89 76.5 (9.6, 5308) 75.8 (9.6, 3127)* 76.3 (10.2, 3024)

30-59 75.6 (9.9, 1488) 74.2 (9.7, 855)* 75.7 (11.3, 797)

<30 73.0 (12.1, 23) 69.9 (11.0, 14) 75.4 (9.7, 16)* p<0.05 compared with chlorthalidone

ALLHAT

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ALLHAT Evaluating Treatment Effects by Subgroup

Significant Test for Treatment x Subgroup Interaction?

Yes NoSignificant treatment difference within 1 or more subgroups?

Yes Interaction No interaction

No Interaction No interaction

Interaction – Use subgroup estimates of treatment effects

No interaction – Use estimate of treatment effect in total population

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6-year rates per 100 (se)& total events / N

Relative Risk (A/C)(95% CI) p valueChlorthalidone Amlodipine

GFR 90 8.7 (0.6)252 / 3648

7.6 (0.7)141 / 2274

0.90 (0.73 - 1.10)0.29

GFR 60-89 10.9 (0.4)740 / 8360

10.9 (0.6)427 / 4850

0.98 (0.87 – 1.10)0.72

GFR 30-59 15.1 (0.9)303 / 2530

16.2 (1.2)192 / 1471

1.10 (0.92 – 1.32)0.29

GFR <30 20.6 (5.1)15 / 83

4.9 (3.4)2 / 45

0.25 (0.06 – 1.08)0.06

Total 11.5 (0.3)1362 / 15,255

11.3 (0.4)798 / 9048

0.98 (0.91 – 1.08)0.81

Differences among treatment group effects by baseline GFR group are not statistically significant.

ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

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Relative Risk (A/C)(95% CI) p valueChlorthalidone Lisinopril

GFR 90 8.7 (0.6)252 / 3648

9.0 (0.8)157 / 2204

1.04 (0.86 – 1.28)0.67

GFR 60-89 10.9 (0.4)740 / 8360

10.6 (0.6)421 / 4899

0.97 (0.86 – 1.09)0.59

GFR 30-59 15.1 (0.9)303 / 2530

14.8 (1.1)173 / 1479

0.99 (0.82 – 1.20)0.95

GFR <30 20.6 (5.1)15 / 83

23.4 (6.3)11 / 54

1.22 (0.56 – 2.67)0.61

Total 11.5 (0.3)1362 / 15,255

11.4 (0.4)796 / 9054

0.99 (0.91 – 1.08)0.81


ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

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GFR 90 10.0 (0.9)133 / 1667

9.2 (1.2)72 / 1026

0.88 (0.66 – 1.18)0.40

GFR 60-89 13.9 (0.8)304 / 2755

14.4 (1.1)184 / 1626

1.00 (0.84 – 1.21)0.96

GFR 30-59 19.2 (1.7)126 / 848

21.9 (2.4)83 / 486

1.13 (0.85 – 1.49)0.40

GFR <30 24.2 (9.2)6 / 33

---0 / 20

---

Total 13.5 (0.6)592 / 5528

13.8 (0.8)358 / 3323

0.99 (0.87 – 1.13)0.93


ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR& Treatment in Diabetic Participants –

Amlodipine vs Chlorthalidone

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GFR 90 10.0 (0.9)133 / 1667

9.7 (1.1)79 / 981

1.02 (0.77 – 1.35)0.87

GFR 60-89 13.9 (0.8)304 / 2755

13.2 (1.1)167 / 1563

0.98 (0.81 – 1.18)0.81

GFR 30-59 19.2 (1.7)126 / 848

17.7 (2.0)70 / 478

1.00 (0.75 – 1.35)0.98

GFR <30 24.2 (9.2)6 / 33

29.4 (10.3)6 / 23

1.43 (0.46 – 4.44)0.54

Total 13.5 (0.6)592 / 5528

12.8 (0.7)339 / 3212

1.00 (0.87 – 1.14)0.97


ALLHAT CHD (Nonfatal MI & Fatal CHD) by Baseline GFR& Treatment in Diabetic Participants –

Lisinopril vs Chlorthalidone

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GFR 90 25.6 (0.9)803 / 3648

25.3 (1.1)487 / 2274

0.97 (0.86 – 1.08)0.56

GFR 60-89 29.6 (0.6)2125 / 8360

31.2 (0.8)1312 / 4850

1.06 (0.99 – 1.14)0.08

GFR 30-59 38.1 (1.2)839 / 2530

41.1 (1.6)522 / 1471

1.10 (0.98 – 1.23)0.09

GFR <30 55.3 (6.4)41 / 83

37.9 (7.8)15 / 45

0.64 (0.35 – 1.16)0.14

Total 30.9 (0.5)3941 / 15,255

32.0 (0.6)2432 / 9048

1.04 (0.99 – 1.09)0.12

Combined CVD = CHD death, nonfatal MI, stroke, coronary revascularization procedures, hospitalized or treated angina, treated or hospitalized HF, and peripheral arterial disease (hospitalized, or outpatient revascularization)


ALLHAT Combined CVD by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

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GFR 90 25.6 (0.9)803 / 3648

29.1 (1.2)526 / 2204

1.11 (0.99 – 1.24)0.06

GFR 60-89 29.6 (0.6)2125 / 8360

31.3 (0.8)1330 / 4899

1.09 (1.02 – 1.17)0.02

GFR 30-59 38.1 (1.2)839 / 2530

41.1 (1.6)525 / 1479

1.13 (1.02 – 1.26)0.03

GFR <30 55.3 (6.4)41 / 83

46.2 (7.5)22 / 54

0.85 (0.50 – 1.43)0.53

Total 30.9 (0.5)3941 / 15,255

33.3 (0.6)2514 / 9054

1.10 (1.05 – 1.16)<0.001

Combined CVD = CHD death, nonfatal MI, stroke, coronary revascularization procedures, hospitalized or treated angina, treated or hospitalized HF, and peripheral arterial disease (hospitalized, or outpatient revascularization)


ALLHAT Combined CVD by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

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GFR 90 27.9 (1.3)402 / 1667

30.4 (1.8)256 / 1026

1.04 (0.89 – 1.22)0.61

GFR 60-89 34.3 (1.1)814 / 2755

35.2 (1.4)499 / 1626

1.03 (0.92 – 1.15)0.62

GFR 30-59 42.4 (2.0)309 / 848

51.2 (2.7)219 / 486

1.25 (1.05 – 1.49)0.01

GFR <30 63.8 (10.3)17 / 33

29.1 (11.1)5 / 20

0.42 (0.15 – 1.13)0.09

Total 33.9 (0.8)1609 / 5528

36.2 (1.0)1030 / 3323

1.06 (0.98 – 1.15)0.12

Combined CVD = CHD death, nonfatal MI, stroke, coronary revasc procedures, hosp or treated angina, treated or hosp HF, and peripheral arterial disease (hosp or outpatient revasc)


ALLHATCombined CVD by Baseline GFR

& Treatment in Diabetic Participants –Amlodipine vs Chlorthalidone

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GFR 90 27.9 (1.3)402 / 1667

31.4 (1.8)257 / 981

1.12 (0.95 – 1.31)0.17

GFR 60-89 34.3 (1.1)814 / 2755

35.0 (1.4)482 / 1563

1.07 (0.96 – 1.20)0.24

GFR 30-59 42.4 (2.0)209 / 848

43.7 (2.6)182 / 478

1.09 (0.90 – 1.30)0.38

GFR <30 63.8 (10.3)17 / 33

54.1 (11.4)11 / 23

0.82 (0.39 – 1.76)0.62

Total 33.9 (0.8)1609 / 5528

35.5 (1.0)985 / 3212

1.08 (1.00 – 1.17)0.049

Combined CVD = CHD death, nonfatal MI, stroke, coronary revasc procedures, hosp or treated angina, treated or hosp HF, and peripheral arterial disease (hosp or outpatient revasc)


ALLHATCombined CVD by Baseline GFR

& Treatment in Diabetic Participants –Lisinopril vs Chlorthalidone

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GFR 90 4.0 (0.4)118 / 3648

3.5 (0.5)70 / 2274

0.95 (0.70 – 1.27)0.71

GFR 60-89 5.2 (0.3)366 / 8360

4.7 (0.4)185 / 4850

0.85 (0.71 – 1.02)0.08

GFR 30-59 7.5 (0.6)149 / 2530

8.7 (1.0)96 / 1471

1.13 (0.87 – 1.46)0.35

GFR <30 8 / 8310.7 (3.6)

4 / 4519.6 (6.8)

0.93 (0.28 – 3.09)0.91

Total 5.6 (0.2)675 / 15,255

5.4 (0.3)377 / 9048

0.93 (0.82 – 1.06)0.28


ALLHAT Stroke by Baseline GFR & Treatment –Amlodipine vs Chlorthalidone

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GFR 90 4.0 (0.4)118 / 3648

5.7 (0.6)101 / 2204

1.43 (1.10 – 1.87)0.01

GFR 60-89 5.2 (0.3)366 / 8360

5.9 (0.4)239 / 4899

1.12 (0.95 – 1.31)0.19

GFR 30-59 7.5 (0.6)149 / 2530

7.5 (0.8)96 / 1479

1.08 (0.83 – 1.40)0.56

GFR <30 10.7 (3.6)8 / 83

19.6 (6.8)7 / 54

1.38 (0.50 – 3.79)0.54

Total 5.6 (0.2)675 / 15,255

6.3 (0.3)457 / 9054

1.15 (1.02 – 1.30)0.02


ALLHAT Stroke by Baseline GFR & Treatment –Lisinopril vs Chlorthalidone

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GFR 90 4.4 (0.6)55 / 1667

3.9 (0.8)33 / 1026

0.98 (0.63 – 1.50)0.92

GFR 60-89 7.7 (0.6)176 / 2755

6.4 (0.7)83 / 1626

0.77 (0.59 – 1.00)0.05

GFR 30-59 8.6 (1.1)60 / 848

11.1 (1.8)41 / 486

1.20 (0.81 – 1.79)0.36

GFR <30 10.8 (6.0)3 / 33

5.6 (5.4)1 / 20

0.53 (0.06 – 5.11)0.58

Total 7.1 (0.4)314 / 5528

6.6 (0.5)172 / 3323

0.90 (0.75 – 1.08)0.26


ALLHATStroke by Baseline GFR


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GFR 90 4.4 (0.6)55 / 1667

7.0 (1.1)53 / 981

1.66 (1.14 – 2.43)0.01

GFR 60-89 7.7 (0.6)176 / 2755

7.8 (0.8)99 / 1563

1.00 (0.78 – 1.28)1.00

GFR 30-59 8.6 (1.1)60 / 848

7.4 (1.5)29 / 478

0.87 (0.56 – 1.36)0.55

GFR <30 10.8 (6.0)3 / 33

27.5 (11.8)4 / 23

1.74 (0.39 – 7.78)0.47

Total 7.1 (0.4)314 / 5528

7.6 (0.6)193 / 3212

1.07 (0.90 – 1.28)0.45


ALLHATStroke by Baseline GFR


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GFR 90 5.1 (0.5)147 / 3648

6.4 (0.6)121 / 2274

1.34 (1.05 – 1.71)0.02

GFR 60-89 6.7 (0.4)435 / 8360

9.8 (0.5)380 / 4850

1.55 (1.34 – 1.79)<0.001

GFR 30-59 12.9 (0.9)247 / 2530

14.9 (1.2)168 / 1471

1.19 (0.97 – 1.47)0.10

GFR <30 21.9 (6.6)12 / 83

16.2 (6.1)6 / 45

0.91 (0.32 – 2.61)0.86

Total 7.7 (0.3)870 / 15,255

10.2 (0.4)706 / 9048

1.40 (1.26 – 1.55)<0.001


ALLHAT Heart Failure by Baseline GFR & Treatment – Amlodipine vs Chlorthalidone

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GFR 90 5.1 (0.5)147 / 3648

6.1 (0.6)110 / 2204

1.25 (0.97 – 1.61)0.08

GFR 60-89 6.7 (0.4)435 / 8360

6.9 (0.4)278 / 4899

1.10 (0.94 – 1.28)0.25

GFR 30-59 12.9 (0.9)247 / 2530

15.4 (1.2)180 / 1479

1.28 (1.04 – 1.57)0.02

GFR <30 21.9 (6.6)12 / 83

24.8 (6.6)11 / 54

1.51 (0.61 – 3.73)0.37

Total 7.7 (0.3)870 / 15,255

8.7 (0.4)612 / 9054

1.20 (1.08 – 1.33)0.001


ALLHAT Heart Failure by Baseline GFR & Treatment – Lisinopril vs Chlorthalidone

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GFR 90 6.5 (0.8)87 / 1667

8.0 (1.1)65 / 1026

1.23 (0.88 – 1.71)0.22

GFR 60-89 9.9 (0.7)203 / 2755

13.4 (1.0)177 / 1626

1.54 (1.24 – 1.90)<0.001

GFR 30-59 15.5 (1.6)100 / 848

22.4 (2.5)85 / 486

1.59 (1.16 – 2.17)0.004

GFR <30 13.5 (6.3)4 / 33

12.5 (8.3)2 / 20

0.81 (0.13 – 4.89)0.81

Total 9.7 (0.5)410 / 5528

13.1 (0.7)347 / 3323

1.46 (1.25 – 1.69)<0.001


ALLHATHeart Failure by Baseline GFR


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GFR 90 6.5 (0.8)87 / 1667

8.1 (1.0)68 / 981

1.35 (0.97 – 1.88)0.07

GFR 60-89 9.9 (0.7)203 / 2755

9.1 (0.9)119 / 1563

1.04 (0.82 – 1.31)0.77

GFR 30-59 15.5 (1.6)100 / 848

20.0 (2.2)75 / 478

1.39 (1.01 – 1.92)0.04

GFR <30 13.5 (6.3)4 / 33

29.1 (10.2)6 / 23

2.56 (0.63 – 10.37)0.19

Total 9.7 (0.5)410 / 5528

10.9 (0.7)284 / 3212

1.21 (1.03 – 1.42)0.02


ALLHATHeart Failure by Baseline GFR


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Discussion

• ALLHAT confirms increased risk for CVD in patients with reduced GFR.

• The overall study results of no difference in the primary outcome for the lisinopril vs. chlorthalidone and amlodipine vs. chlorthalidone comparisons was consistent across diabetes, GFR, and diabetes-GFR subgroups.

ALLHAT

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Conclusion

• Amlodipine and lisinopril are not superior to chlorthalidone in preventing fatal CHD/non fatal MI

• Chlorthalidone and amlodipine are similar but chlorthalidone is superior to lisinopril in reducing combined CVD events independent of level of renal function.

ALLHAT

In high risk hypertensive patients with impaired renal function:

6/5/2006 - 1 1 cardiovascular disease outcomes in hypertensive patients stratified by baseline...

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