CARE Sub-study

18 Aug, 10

CARE Sub-study

Sub-study 1 - Cholesterol and Recurrent Events

Introduction

Long term effects of pravastatin on plasma concentration of C reactive protein

Purpose

To determine whether long term therapy with pravastatin reduces the levels of the inflammatory marker, C-reactive protein.

Design

As per CARE

Patients

472 randomly selected participants in CARE in whom C-reactive protein was measured at baseline and at 5 years

and who had remained free of recurrent vascular events during follow-up.

Follow-up

5 years

Treatment Regimen

As per CARE

Results

While C-reactive protein levels increased over time in placebo patients (median change = +4.2%; p=0.2 and mean change =+0.07 g/dL; p=0.04), they decreased in pravastatin patients (median change =17.4%; p=0.004 and mean change =-0.07 mg/dL; p=0.002). Median, mean, and absolute change in C-reactive protein were significantly lower in the pravastatin group at 5 years (-21.6%; p=0.007; -37.8%, p=0.002; and 0.137 g/dL; p=0.003, respectively).
The changes in C-reactive protein over time did not correlate with change in LDL cholesterol among pravastatin or placebo treated patients.
There was also a lack of a correlation between change in C-reactive protein and changes in total cholesterol or HDL levels.
Pravastatin reduced C-reactive protein levels at all LDL change increments.

Conclusions

In post myocardial infarction patients, C-reactive protein levels tended to increase over 5 years in patients receiving standard therapy plus placebo; pravastatin decreased C-reactive protein levels independent of the degree of lipid improvement.

Circulation 1999;100:230-5

Sub-study 2 - Cholesterol And Recurrent Events

Introduction

Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range.

Purpose

To determine whether lipid lowering with pravastatin decreases recurrent cardiovascular events in patients 65 years and older.

Design

As per CARE

Patients

Subset of patients from the CARE Trial who were 65-75 years old. 1283 post MI patients. Total cholesterol level had to be < 240 mg/dL and LDL cholesterol of 115-174 mg/dL.

Follow-up

5 years

Treatment Regimen

As per CARE

Results

At 5 years major coronary events (coronary death, nonfatal MI, PTCA or CABG) were reduced in the pravastatin group from 28.1% in placebo patients to 19.7% in pravastatin patients (relative risk reduction = 32%; p <0.001).
Death from coronary artery disease was reduced from 10.3% in placebo patients to 5.8% in the pravastatin group (relative risk reduction = 45%; p = 0.004).
Stroke was reduced from 7.3% in placebo patients to 4.5% in the pravastatin group (relative risk reduction = 40%; p=0.03).

Conclusion

In older post myocardial infarction patients with average cholesterol levels, pravastatin decreased the rate of major coronary heart disease events and stroke

Ann Intern Med 1998;129:681-9

Sub-study 3 - Cholesterol And Recurrent Events

Introduction

Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels.

Purpose

To determine whether inflammation plays a role in recurrent events following myocardial infarction.

Design

Control substudy of CARE trial.

Patients

391 patients in CARE trial who developed recurrent non-fatal MI or fatal coronary event (cases), and comparison to equal number of controls that were age and sex matched but remained free of recurrent cardiac event (controls).

Follow-up

As per CARE

Treatment Regimen

As per CARE

Results

C-reactive protein (CRP) and serum amyloid A (SAA), markers of inflammation, were highest among cases vs controls.
Patients with highest quintiles had a relative risk of recurrent events that was 75% higher than patients in the lowest quintile (p=0.02).
Highest risk of recurrent events occurred in the placebo patients with elevations of both CRP and SAA.
Assessment of stratified analysis revealed that while the association between inflammation and the risk of recurrent events was increased in patients randomized to placebo (RR=2.11, p=0.048), this association was not significant in patients randomized to pravastatin (RR=1.29, p=0.5).

Conclusion

Inflammation assessed by elevations of C-reactive protein and serum amyloid following myocardial infarction is associated with recurrent cardiac events; pravastatin may reduce the risk.

Circulation 1998;98:839-44

Sub-study 4 - Cholesterol And Recurrent Events

Introduction

Cardiovascular events and their reduction with pravastatin in diabetic and glucose intolerant myocardial infarction survivors with average cholesterol levels. Subgroup analysis in the Cholesterol and Recurrent Events (CARE) trial.

Purpose

To determine whether pravastatin prevented recurrent cardiovascular events in diabetic patients

Design

As per CARE trial

Patients

586 patients in the CARE trial with diabetes

Follow-up

5 years

Treatment Regimen

As per CARE trial

Results

Pravastatin reduced LDL cholesterol by 27% in the diabetic group and 28% in the nondiabetic group.
Pravastatin induced a 25% reduction in coronary events (coronary heart disease death, nonfatal myocardial infarction, CABG and PTCA) p=0.05; it reduced the risk for revascularisation procedures by 32% (p=0.04). Because of a greater coronary event rate in the diabetic group, pravastatin resulted in a greater absolute risk reduction in diabetic vs nondiabetic group (8.1% vs 5.2%).

Conclusion

Both diabetic and nondiabetic patients with elevated fasting glucose levels are at risk for recurrent coronary events post infarction; pravastatin can reduce these events.

Circulation 1998;98:2513-9