Lipid Lowering Substudy Trial of the Lipid Lowering Substudy Trial of the

Antihypertensive and Lipid-Lowering Treatment to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialPrevent Heart Attack Trial

Lipid Lowering Substudy Trial of the Lipid Lowering Substudy Trial of the

Antihypertensive and Lipid-Lowering Treatment to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialPrevent Heart Attack Trial

JAMA 2002;288:2998-3007JAMA 2002;288:2998-3007

ALLHAT- LLTALLHAT- LLT

www. Clinical trial results.org

10,355 patients with moderate hypercholesterolemia All patients enrolled in the ALLHAT antihypertensive trial Fasting LDL-C level of 120-189 mg/dL with no known CHD or 100-129 mg/dL with

known CHD Fasting triglyceride levels <350 mg/dL NHLBI funded trial

10,355 patients with moderate hypercholesterolemia All patients enrolled in the ALLHAT antihypertensive trial Fasting LDL-C level of 120-189 mg/dL with no known CHD or 100-129 mg/dL with

known CHD Fasting triglyceride levels <350 mg/dL NHLBI funded trial

Endpoints: Primary – All-cause mortality Fatal coronary heart

disease and nonfatal MI Secondary – Fatal coronary heart disease and nonfatal

MI, stroke, CHF, cancer Mean follow-up 4.8 years

Endpoints: Primary – All-cause mortality Fatal coronary heart

disease and nonfatal MI Secondary – Fatal coronary heart disease and nonfatal

MI, stroke, CHF, cancer Mean follow-up 4.8 years

ALLHAT- LLTALLHAT- LLTALLHAT- LLTALLHAT- LLT

JAMA 2002;288:2998-3007JAMA 2002;288:2998-3007

Pravastatin 40 mg/day(n=5,170)

Pravastatin 40 mg/day(n=5,170)

Usual Careat discretion of primary care physician

(n=5,185)

Usual Careat discretion of primary care physician

(n=5,185)

www. Clinical trial results.org

5.3%5.8%

0%

2%

4%

6%

8%

10%

5.3%5.8%

0%

2%

4%

6%

8%

10%

14.9% 15.3%

0%

5%

10%

15%

20%

14.9% 15.3%

0%

5%

10%

15%

20%

All Cause MortalityRR = 0.99p = 0.88

All Cause MortalityRR = 0.99p = 0.88

ALLHAT- LLT: Clinical EndpointsALLHAT- LLT: Clinical EndpointsALLHAT- LLT: Clinical EndpointsALLHAT- LLT: Clinical Endpoints

PravastatinPravastatin Usual CareUsual Care

9.3%

10.4%

0%

5%

10%

15%

9.3%

10.4%

0%

5%

10%

15%

Fatal Heart Diseaseor Nonfatal MI

RR = 0.91p = 0.16

Fatal Heart Diseaseor Nonfatal MI

RR = 0.91p = 0.16

StrokeRR = 0.91p = 0.31

StrokeRR = 0.91p = 0.31

JAMA 2002;288:2998-3007JAMA 2002;288:2998-3007

PravastatinPravastatin Usual CareUsual Care PravastatinPravastatin Usual CareUsual Care

www. Clinical trial results.org

223.7205.9

0

50

100

150

200

250223.7

205.9

0

50

100

150

200

250223.7

184.3

0

50

100

150

200

250223.7

184.3

0

50

100

150

200

250

Pravastatin 17.2%

Pravastatin 17.2%

ALLHAT- LLT: Total CholesterolALLHAT- LLT: Total CholesterolALLHAT- LLT: Total CholesterolALLHAT- LLT: Total Cholesterol

BaselineBaseline 4 Year Follow-up4 Year Follow-up

Usual Care 7.6%

Usual Care 7.6%

mg

/dL

BaselineBaseline 4 Year Follow-up4 Year Follow-up

JAMA 2002;288:2998-3007JAMA 2002;288:2998-3007

mg

/dL

www. Clinical trial results.org

145.5

128.7

0

50

100

150

200

145.5

128.7

0

50

100

150

200

145.6

104.5

0

50

100

150

200

145.6

104.5

0

50

100

150

200

Pravastatin 27.7%

Pravastatin 27.7%

ALLHAT- LLT: LDL CholesterolALLHAT- LLT: LDL CholesterolALLHAT- LLT: LDL CholesterolALLHAT- LLT: LDL Cholesterol

BaselineBaseline 4 Year Follow-up4 Year Follow-up

Usual Care 11.0%

Usual Care 11.0%

mg

/dL

BaselineBaseline 4 Year Follow-up4 Year Follow-up

JAMA 2002;288:2998-3007JAMA 2002;288:2998-3007

mg

/dL

www. Clinical trial results.org

ALLHAT- LLT: SummaryALLHAT- LLT: SummaryALLHAT- LLT: SummaryALLHAT- LLT: Summary

Despite moderate reduction in cholesterol with pravastatin, there was no difference in mortality, CHD or stroke compared with usual care for moderate hypercholesterolemia

– High crossover rate from usual care to statin treatment (8% at year 2 and 17% at year 4) may explain the only moderate difference in cholesterol reduction and the lack of clinical benefit between the two arms

– A greater benefit was observed in blacks than in nonblacks with pravastatin for fatal heart disease or nonfatal MI endpoint (RR 0.73 vs 1.02, p=0.03)

– Lack of clinical benefit with statin therapy contrasts with other large statin trials (4S, CARE, LIPID, and PROSPER)

– Meta-analysis of 9 large statin trials including ALLHAT-LLT shows CHD events 27% and mortality 14% with statin therapy

Despite moderate reduction in cholesterol with pravastatin, there was no difference in mortality, CHD or stroke compared with usual care for moderate hypercholesterolemia

– High crossover rate from usual care to statin treatment (8% at year 2 and 17% at year 4) may explain the only moderate difference in cholesterol reduction and the lack of clinical benefit between the two arms

– A greater benefit was observed in blacks than in nonblacks with pravastatin for fatal heart disease or nonfatal MI endpoint (RR 0.73 vs 1.02, p=0.03)

– Lack of clinical benefit with statin therapy contrasts with other large statin trials (4S, CARE, LIPID, and PROSPER)

– Meta-analysis of 9 large statin trials including ALLHAT-LLT shows CHD events 27% and mortality 14% with statin therapy