Myocardial infarction: pravastatin reduced coronary events post MI even in patients without high cholesterol.

Clinical bottom line (level 1b)

  1. Patients following a myocardial infarction with 'normal' cholesterol levels, who took pravastatin had fewer heart attacks and deaths from coronary heart disease than those given placebo (NNT = 33 at 5 years) .
Sacks et al: New England Journal of Medicine 1996; 335 (14): 1001-1009
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 13 centres in Canada and 67 US hospitals

4159 patients (aged mean 59 years, 86% male) men and post-menopausal women with acute myocardial infarction between 3 and 20 months previously

Excluded if
  • aged <21 or >75 years
  • cholesterol 240 mg/dl or more
  • LDL <115 or >174 mg/dl
  • glucose >12.2 mmol/l
  • LV function <25%
  • CCF


Note:
  • Initial blood measurements at least eight weeks after MI and four weeks after commencing on lipid lowering diet (National Education Cholesterol Diet step 1).
  • Had cholesterol, LDL and TAG measured at 0, 6, 12 weeks after commencing medication. If LDL still >4.5 mmol/l then, started on step 2 of diet. If still raised, then had 8-16 mg of cholestyramine to lower LDL to <4.5 mmol/l. If still raised, physician took further steps as required.


Control Group: (n = 2078, 2078 analysed): placebo
Experimental Group: (n = 2081, 2081 analysed): pravastatin 40 mg once daily

90% followed for 5 years vital status known in 99.97%
Outcome notes:
  • non-fatal MI or death from coronary heart disease : MI confirmed by rise in cardiac enzymes

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
non-fatal MI or death from coronary heart disease 5 years 274
(13.2%)		 208
(10.0%)		 24%
(10% to 36%)		 3.19%
(1.05% to 4.96%)		 33
(20 to 95)
death from coronary heart disease 5 years 118
(5.68%)		 96
(4.61%)		 19%
(-6% to 38%)		 1.07%
(-0.28% to 2.41%)		 94
(NNT = 42 to infinity;
NNH = 360 to infinity)
non-fatal MI 5 years 172
(8.28%)		 125
(6.01%)		 27%
(9% to 42%)		 2.27%
(0.71% to 3.83%)		 44
(26 to 140)
CABG or PTCA 5 years 391
(18.8%)		 294
(14.1%)		 23%
(9% to 35%)		 4.69%
(2.44% to 6.94%)		 21
(14 to 41)
stroke 5 years 78
(3.75%)		 54
(2.59%)		 31%
(3% to 51%)		 1.06%
(0.09% to 2.22%)		 86
(45 to 1069)

Pravastatin reduced LDL by 32% (mean 3.6 mmol/l to mean 2.5 mmol/l).

Comments

  1. Large number of men in the study - how applicable are the results in women?
  2. Data failed to show any reduction for coronary heart disease mortality alone - but underpowered in this respect.

Citation

  1. Sacks FM, et al: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New England Journal of Medicine 1996; 335 (14): 1001-1009
Contributor: Chris Ball and Bob Phillips, July 2000
Reviewer: Dwight Peretz

Clinical Question.
Patient post MI with 'normal' cholesterol
Intervention or Exposure pravastatin
Comparison placebo
Outcome further MI