Eileen A Kelly
August 2,1996
CLINICAL SCENARIO/QUESTION:
A 62 yo WM presents to continuity clinic for a new work up. His PMH is unremarkable, he is a non-smoker. Routine laboratory evaluation reveals a serum teal cholesterol of 265, LDL of 177 and HDL of 45. Is there any data to support that the use of cholesterol lowering agents in this pt. will reduce his cardiovascular morbidity and mortality?
MESH: cholesterol, prevention, cardiovascular
CLINICAL BOTTOM LINES:
1. In men aged 45-64 with LDL 192+/-17 and no history of MI, pravastatin 40 mg qhs:
a) *decreases the incidence of nonfatal MI and death from cardiovascular causes
b) effect on tidal mortality (from all causes combined) is of borderline statistical
significance, p= .5
c) significantly decreases total cholesterol
d) significantly decreases LDL cholesterol
e) modestly increases HDL cholesterol
2. There was no association between the use of pravastatin and increased risk of death from non-cardiovascular causes.
THE EVIDENCE:
1. Prospective, double-blinded RCT of 6595 men, age 45-64, with hypercholesterolemia
(mean total cholesterol 272+/-23, mean LDL 192+/-17)and no prior history of MI; Pts. were
randomized to receive either 40 mg pravastatin or placebo qd; average f/u 5yrs.
| Variable | Placebo (N=3293) | Pravastatin (N=3302) | p value | Rise Reduction with Pravastatin (95% CI) |
| Definite coronary events | ||||
| Nonfatal MI or death from CHD | 248 (7.9) | 174 (5.5) | <0.001 | 31 (17 to 43) |
| Nonfatal MI (silent MIs omitted) or death from CHD | 218 (7.0) | 150 (4.7) | <0.001 | 33 (17 to 45) |
| Nonfatal MI | 204 (6.5) | 143 (4.6) | <0.001 | 31 (14 to 45) |
| Death from CHD | 52 (1.7) | 38 (1.2) | 0.13 | 28 (-10 to 52) |
| Definite + suspected coronary events | ||||
| Nonfatal MI or death from CHD | 295 (9.3) | 215 (6.8) | <0.001 | 29 (15 to 40) |
| Nonfatal MI (silent MIs omitted) or death from CHD | 240 (7.6) | 166 (5.3) | <0.001 | 32 (17 to 44) |
| Nonfatal MI | 246 (7.8) | 182 (5.8) | 0.001 | 27 (12 to 40) |
| Death from CHD | 61 (1.9) | 41 (1.3) | 0.042 | 33 (1 to 55) |
| Other events | ||||
| Coronary angiography | 128 (4.2) | 90 (2.8) | 0.007 | 31 (10 to 47) |
| PTCA or CABG | 80 (2.5) | 51 (1.7) | 0.009 | 37 (11 to 56) |
| Fatal or nonfatal stroke | 51 (1.6) | 46 (1.6) | 0.57 | 11 (-33 to 40) |
| Incident cancer | 103 (3.3) | 116 (3.7) | 0.55 | -8 (-41 to 17) |
| Death from other causes | ||||
| Other cardiovascular causes (including stroke) | 12 | 9 | __ | __ |
| Suicide | 1 | 2 | __ | __ |
| Trauma | 5 | 3 | __ | __ |
| Cancer | 49 (1.5) | 44 (1.3) | 0.56 | 11 (-33 to 41) |
| All other causes | 7 | 7 | __ | __ |
| Death from all cariovascular causes |
73 (2.3) | 50 (1.6) | 0.033 | 32 (3 to 53) |
| Death from noncariovasular cause | 62 (1.9) | 56 (1.7) | 0.54 | 11 (-28 to 38) |
| Death from any cause | 135 (4.1) | 106 (3.2) | 0.051 | 22 (0 to 40) |
COMMENTS:
1. Large, powerful study, well-designed; subgroups assessed (smoking prior vascular
dz,etc.); no women; West of Scotland is a high risk area in terms of cardiac events.
2. Study must be placed into perspective in terms of applicability to our patient
population; still need to risk stratify pts.
3. Cost: UNC: HMG CoA(simvastatin)40 mg qd=$63.19/mo
Revco: pravastatin 40mg qd = $111.19/mo; simvastatin 40 mg qd=$98.29/mo
4. Long-term safety of the statins are unknown.
REFERENCES:
1. Shepherd J. Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, et al. Prevention of
coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland
Study Group. New Engl J Med 1995;333:1301-7.
2. West of Scotland Coronary Prevention Study Group. A coronary primary prevention
study of Scottish men age 45-64 years: trial design. J Clin Epidemiol 1992;45:849-60.