PROSPER trial

PROSPER study, 2002
	download pdf: pravastatin \| cholesterol lowering intervention for cardiovascular prevention

Treatments

Studied treatment

pravastatin 40mg daily

Control treatment

placebo

Treatments description

LDL change	-34%
HDL change	+5%

Patients

men and women aged 70-82 years with a history of, or risk factors for, vascular disease

Inclusion criteria

men and women aged 70–82 years; either pre-existing vascular disease (coronary, cerebral, or peripheral) or raised risk of such disease because of smoking, hypertension, or diabetes; total cholesterol between 4·0–9·0 mmol/L; triglyceride less than 6·0 mmol/L

Exclusion criteria

poor cognitive function (mini mental state examination score <24)

Baseline characteristics

Age (mean), yrs	75.35
Women (%)	51.7%
prior MI or CHD (%)	13.35
Total cholesterol (mmol/l)	5.7 mmol/L
LDL (mmol/l)	3.8 mmol/L
HDL (mmol/l)	1.3 mmol/L
Diabetes(%)	10.75
BMI (kg/m2)	26.8
Stroke history	11.15

Method and design

Randomized effectives	2891 / 2913 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	3.2 years
Lost to follow-up	ND
Number of centre	multicenter
Geographic area	Ecosse, Irelande, Pays bas
Hypothesis	Superiority
Primary endpoint	death, MI , stroke

Results

Endpoints and data reported in the trial's publication(s)

Endpoint	Events (%)		Relative Risk	95% CI
Endpoint	Studied treat.	Control treat.	Relative Risk	95% CI
Non-fatal myocardial infarction	222 / 2891 (7,7%)	254 / 2913 (8,7%)	0,88	[0,74;1,05]
Non-fatal myocardial infarction	222 / 2891 (7,7%)	254 / 2913 (8,7%)	0,88	[0,74;1,05]
CHD death or non-fatal MI (excluding silent and unrecognised events)	193 / 2891 (6,7%)	246 / 2913 (8,4%)	0,79	[0,66;0,95]
Non-fatal stroke	116 / 2891 (4,0%)	119 / 2913 (4,1%)	0,98	[0,76;1,26]
Transient ischaemic attack	77 / 2891 (2,7%)	102 / 2913 (3,5%)	0,76	[0,57;1,02]
Percutaneous transluminal coronary angioplasty, CABG	39 / 2891 (1,3%)	48 / 2913 (1,6%)	0,82	[0,54;1,25]
Peripheral arterial surgery/angioplasty	35 / 2891 (1,2%)	45 / 2913 (1,5%)	0,78	[0,51;1,22]
All cardiovascular events	454 / 2891 (15,7%)	523 / 2913 (18,0%)	0,87	[0,78;0,98]
Fatal or non-fatal stroke or transient ischaemic attack	204 / 2891 (7,1%)	212 / 2913 (7,3%)	0,97	[0,81;1,17]
Heart failure hospitalisation	112 / 2891 (3,9%)	122 / 2913 (4,2%)	0,93	[0,72;1,19]
Coronary heart disease deaths	94 / 2891 (3,3%)	122 / 2913 (4,2%)	0,78	[0,60;1,01]
Stroke deaths	22 / 2891 (0,8%)	14 / 2913 (0,5%)	1,58	[0,81;3,09]
Vascular deaths	135 / 2891 (4,7%)	157 / 2913 (5,4%)	0,87	[0,69;1,08]
Non-vascular deaths	163 / 2891 (5,6%)	149 / 2913 (5,1%)	1,10	[0,89;1,37]
Cancer deaths	115 / 2891 (4,0%)	91 / 2913 (3,1%)	1,27	[0,97;1,67]
Trauma or suicide deaths	2 / 2891 (0,1%)	7 / 2913 (0,2%)	0,29	[0,06;1,38]
All causes deaths	298 / 2891 (10,3%)	306 / 2913 (10,5%)	0,98	[0,84;1,14]
CHD death or non-fatal MI, stroke	408 / 2891 (14,1%)	473 / 2913 (16,2%)	0,87	[0,77;0,98]
CHD death or non-fatal MI	292 / 2891 (10,1%)	356 / 2913 (12,2%)	0,83	[0,71;0,96]
Fatal or non-fatal stroke	135 / 2891 (4,7%)	131 / 2913 (4,5%)	1,04	[0,82;1,31]

Endpoints used by the meta-analysis and data retained for this trial

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

Coronary event

292 / 2891
356 / 2913
0,83 [0,71;0,96]

All cause death

298 / 2891
306 / 2913
0,98 [0,84;1,14]

Cardiovascular death

135 / 2891
157 / 2913
0,87 [0,69;1,08]

cardiovascular events

408 / 2891
473 / 2913
0,87 [0,77;0,98]

Fatal stroke

22 / 2891
14 / 2913
classic 1,58 [0,81;3,09]

new-onset diabetes

165 / 2510
127 / 2513
1,30 [1,04;1,63]

Coronary death

94 / 2891
122 / 2913
0,78 [0,60;1,01]

stroke (fatal and non fatal)

135 / 2891
131 / 2913
1,04 [0,82;1,31]

MACE

454 / 2891
523 / 2913
0,87 [0,78;0,98]

Non fatal MI

222 / 2891
254 / 2913
0,88 [0,74;1,05]

Rhabdomyolysis

0 / 2891
0 / 2913
classic 1,01 [0,00;257,51]

Death from cancer

115 / 2891
91 / 2913
1,27 [0,97;1,67]

Myopathy

36 / 2891
32 / 2913
1,13 [0,71;1,82]

Coronary death and non fatal MI

292 / 2891
356 / 2913
0,83 [0,71;0,96]

cardiac death

94 / 2891
122 / 2913
0,78 [0,60;1,01] 0 2 1.0

Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
Relative risks
Endpoint	Studied treat.	Control treat.	Relative Risk	95% CI	Endpoint definition in the trial	Ref
Coronary event	292 / 2891 (10,1%)	356 / 2913 (12,2%)	0,83	[0,71;0,96]		1757
All cause death	298 / 2891 (10,3%)	306 / 2913 (10,5%)	0,98	[0,84;1,14]
Cardiovascular death	135 / 2891 (4,7%)	157 / 2913 (5,4%)	0,87	[0,69;1,08]
cardiovascular events	408 / 2891 (14,1%)	473 / 2913 (16,2%)	0,87	[0,77;0,98]		1757
Fatal stroke	22 / 2891 (0,8%)	14 / 2913 (0,5%)	1,58	[0,81;3,09]
new-onset diabetes	165 / 2510 (6,6%)	127 / 2513 (5,1%)	1,30	[1,04;1,63]	sub group	12095
Coronary death	94 / 2891 (3,3%)	122 / 2913 (4,2%)	0,78	[0,60;1,01]
stroke (fatal and non fatal)	135 / 2891 (4,7%)	131 / 2913 (4,5%)	1,04	[0,82;1,31]
MACE	454 / 2891 (15,7%)	523 / 2913 (18,0%)	0,87	[0,78;0,98]		1757
Non fatal MI	222 / 2891 (7,7%)	254 / 2913 (8,7%)	0,88	[0,74;1,05]
Rhabdomyolysis	0 / 2891 (0,0%)	0 / 2913 (0,0%)	1,01	[0,02;50,77]
Death from cancer	115 / 2891 (4,0%)	91 / 2913 (3,1%)	1,27	[0,97;1,67]
Myopathy	36 / 2891 (1,2%)	32 / 2913 (1,1%)	1,13	[0,71;1,82]
Coronary death and non fatal MI	292 / 2891 (10,1%)	356 / 2913 (12,2%)	0,83	[0,71;0,96]
cardiac death	94 / 2891 (3,3%)	122 / 2913 (4,2%)	0,78	[0,60;1,01]		1757
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 1757: Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG,Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.Lancet 2002; 360:1623-30 12095: Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, TognonStatins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.Lancet 2010 Feb 27;375:735-742 0:

Endpoint	Events rate		Absolute risk reduction (ARR)
Absolute risk reduction
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
Coronary event	10,10%	12,22%	-21,2‰
All cause death	10,31%	10,50%	-2,0‰
Cardiovascular death	4,67%	5,39%	-7,2‰
cardiovascular events	14,11%	16,24%	-21,2‰
Fatal stroke	7,61‰	4,81‰	2,8‰
new-onset diabetes	6,57%	5,05%	1,5%
Coronary death	3,25%	4,19%	-9,4‰
stroke (fatal and non fatal)	4,67%	4,50%	1,7‰
MACE	15,70%	17,95%	-22,5‰
Non fatal MI	7,68%	8,72%	-10,4‰
Death from cancer	3,98%	3,12%	8,5‰
Myopathy	1,25%	1,10%	1,5‰
Coronary death and non fatal MI	10,10%	12,22%	-21,2‰
cardiac death	3,25%	4,19%	-9,4‰

Meta-analysis of all similar trials:

cholesterol lowering intervention in cardiovascular prevention for elderly

cholesterol lowering intervention in cardiovascular prevention for high risk patients with or without LDL cholesterol elevation

cholesterol lowering intervention in cardiovascular prevention for all chronical situations

Reference(s)

Trials register #

PROSPER study, 2002