Simvastatin-Niacin or Antioxidant Vitamins for the Prevention of Coronary Disease

Bill Meikrantz

December 7, 2001

 

Brown, B.G. et al. N Engl J Med 2001;345:1583-92.

 

Background: Lipid-modifying therapy and antioxidant vitamins are both thought to have benefit in secondary prevention of CAD. 

Study Question: This study compared treatment with simvastatin-niacin and antioxidant vitamin therapy alone and in combination in patients with CAD and low HDL.  

Results: Simvastatin plus niacin provided clinical and angiographically measurable benefits.  Antioxidants alone had no benefit.  Addition of antioxidants to simvastatin-niacin diminished the benefits of drug therapy.

 

Study population: 160 enrolled with (1) clinical CAD (MI, PCI, confirmed angina) and (2) at least 3 stenoses of >30% or one stenosis >50%.  Men < 63; women < 70.  All had low HDL, LDL < 145, and TG < 400.  454 initially eligible, 294 not enrolled: lipid levels outside range, previous CABG, severe HTN, recent gout, liver dz, thyroid dz, kidney dz, uncontrolled diabetes, or declined to participate.

 

Rx: Simvastatin-niacin (doses adjusted to achieve target lipid levels); vitamin E + vitamin C + beta-carotene + selenium; combination; placebo. 

 

Endpoints (at 3 y): (1) clinical (death from cardiovascular causes, non-fatal infarction, revascularization procedure), (2) angiographic re-assessment of coronary artery stenosis

 

Validity:

 

  1. Assignment of patients to treatment groups was randomized and produced well-balanced groups (gender, hypertension, tobacco, previous MI, previous PTCA, diabetes, BMI, Framingham risk score, mean severity of proximal stenosis at base line; Table 1).
  2. Followup: 2 patients died, 12 withdrew from the study (2 because of niacin intolerance).
  3. Intention-to-treat analysis
  4. Pts & clinicians blinded to treatment
  5. Groups treated similarly apart from intervention

 

Results (Table 3, 4; Fig. 2):

 

Placebo

(N=34)

Simvastatin-niacin (N=33)

Antioxidants (N=39)

Combined (N=40)

Mean %stenosis in proximal arteries

+3.9

-0.4

+1.8

+0.7

 

(N=38)

(N=38)

(N=42)

(N=42)

Composite Clinical  (number of patients)

9

1*

9

6

 

Size and precision of treatment effect:            Clinical endpoint:             ARR 21% (7-35%)            NNT 5            (3-14)

                                                                        Arteriographic endpoint:                      P<.001

 

Note inclusion of multiple secondary endpoints (e.g., lipoprotein oxidation, change in lipoprotein subtypes, apolipoproteins, etc.; Table 2).

 

Conclusion: Lipid-modifying agents are effective in secondary prevention of CAD.  Antioxidants alone are of no benefit, and may counteract the beneficial effect of lipid-modifying agents.