Meta-analysis: Antidyslipidemic therapy prevents myocardial infarction and death
ACP J Club. 1997 Jan-Feb;126:4. doi:10.7326/ACPJC-1997-126-1-004
Rembold CM. Number-needed-to-treat analysis of the prevention of myocardial infarction and death by antidyslipidemic therapy. J Fam Pract.1996 Jun;42:577-86.
To evaluate the benefits of treating dyslipidemia to prevent morbidity and mortality from cardiovascular disease.
Studies were identified using MEDLINE (1966 through 1995) with the keywords atherosclerosis, coronary artery disease, and regression, and from recent literature reviews.
Randomized studies were selected if they involved standard antidyslipidemic therapy (diet, pharmaceutical agents, or surgery) and included patients with multiple atherosclerosis risk factors but no known coronary atherosclerosis (primary prevention studies), patients with known atherosclerosis (secondary prevention studies), or patients with a previous myocardial infarction (MI) (tertiary studies).
Data were extracted on risk factors for coronary atherosclerosis, treatment type and duration, results of angiography, and absolute risk reduction (ARR) for MI and cardiovascular death.
In 6 trials of primary prevention (excluding 1 trial that evaluated clofibrate, which is no longer used), standard antidyslipidemic therapy reduced the total cholesterol level by 15% and led to an ARR of 1.6% for nonfatal MI, 0.5% for cardiovascular death, and 0.5% for all-cause mortality. This ARR means that 53 patients would need to be treated (NNT) for 4.8 years with standard antidyslipidemic therapy (rather than usual care) to prevent 1 additional nonfatal MI or cardiovascular death (95% CI 41 to 81). The NNT to prevent 1 additional death from all causes is 190 (CI 106 to 3425). In 23 trials of secondary and tertiary prevention, active treatment using various dietary and pharmacologic agents for a mean of 4.9 years reduced the total cholesterol level by 18% and led to an ARR of 6.4% for nonfatal MI or cardiovascular death (NNT 16, CI 13 to 19) and 2.7% for all-cause mortality (NNT 37, CI 26 to 64). 13 secondary and tertiary prevention trials that lasted for 2.6 years reported angiographic data. The NNT to prevent 1 additional progression of coronary atherosclerosis was 7 (CI 6 to 9) and to induce 1 additional regression of coronary atherosclerosis was 10 (CI 7 to 17). Similar benefits on atherosclerosis progression and regression were observed in 9 secondary and tertiary trials evaluating 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors.
5 years of treatment of dyslipidemia in patients with and without known atherosclerosis prevents myocardial infarction or cardiovascular death with a number needed to treat of 16 patients and 53 patients, respectively.
Sources of funding: In part, Lucille P. Markey Charitable Trust and the U.S. Public Health Service.
For article reprint: Dr. C.M. Rembold, Box 146, Cobb 1034, Hospital Drive, Cardiovascular Division, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA. FAX 804-924-9604.
NNT analysis is a useful tool for clinical decision making (1); the higher the risk for patients the greater the potential benefit from treatment. The Table compares the NNT for cholesterol reduction in secondary (2) and primary (3) prevention trials with primary prevention in isolated systolic hypertension (4).
53 as the NNT for primary prevention of MI or cardiovascular death, calculated by Rembold and colleagues, is very close to that of the West of Scotland trial (3); similarly, 16 as the NNT for secondary prevention is comparable to the NNT in the Scandinavian Simvastatin Survival Study (4S) trial (2).
If we assume that our secondary prevention patients have risks and benefits similar to those of patients in the 4S trial (2), an NNT of 11 compares favorably with the NNT for treatment of isolated systolic hypertension.
Therefore, the message from these studies is to focus on which types of patients to treat and not on which level of cholesterol to treat. Based on this, high-risk patients will benefit most from cholesterol reduction.
|Study (Reference)||Event Prevented||NNT|
|4S trial (2)||1 MI in 6 years||11|
|West of Scotland (3)||1 MI in 6 years*||55|
|SHEP (4)||1 stroke in 6 years*||26|
*Adjusted to 6 years assuming linear proportions. SHEP = Systolic Hypertension in the Elderly Program.
J. David Spence, MD
Robarts Research InstituteLondon, Ontario, Canada