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Patient-oriented gains with LDL lowering are small
Clinical Question
What is the impact of low-density lipoprotein cholesterol reduction on the individual risks of myocardial infarction, stroke, and overall mortality?
Bottom line
The authors of this meta-analysis shine a light on something that has been known for quite some time but is often overshadowed by hope: reducing LDL levels with statins provides only a small reduction in the person's likelihood of dying (0.8% reduction) or experiencing myocardial infarction (1.3%) or stroke (0.4%). Too often we are given relative risk reductions or a bundling together of these outcomes with other lesser outcomes, which leads to an inflated sense of importance attributed to cholesterol treatment. In addition, the authors also found a small and inconsistent relationship between more aggressive lowering of LDL cholesterol and these outcomes, which is contrary to what many (US) guidelines would have us believe. 1a-
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Unknown/not stated
Setting: Outpatient (any)
Synopsis
These authors followed PRISMA guidelines to report the results of their meta-analysis evaluating the relationship between low-density lipoprotein (LDL) cholesterol lowering and individual, patient-oriented outcomes. By searching 2 databases (1987 through June 2021), the authors identified 21 studies of primary and secondary prevention. Overall risk of bias in the studies was low. As compared with placebo in 19 studies (n = 132,763), statin treatment produced a 0.8% overall reduction (95% CI 0.4% - 1.2%) in the likelihood of death due to any cause over the course of the study (which was typically 3 years - 6 years). The likelihood of a heart attack decreased 1.3% (0.9% - 1.7%) in 18 studies of 121,190 participants, and stroke was decreased by 0.4% (0.2% - 0.6%) in 128,086 patients. For primary prevention, these attributable risk reductions were lower — 0.6%, 0.7%, and 0.3% — and for secondary prevention, these risk reductions were a little higher — 0.9%, 2.2%, and 0.7%. There was an inconsistent relationship across the studies between the degree of LDL lowering and prevention of the outcome. There was statistical heterogeneity among the studies, which likely means that there were differences among the study populations. The authors caution against calculating numbers needed to treat because of this heterogeneity, but I'm going to do it anyway: 88 to 250 people need to be treated for 1 additional person to be alive at the end of several years.
Reviewer
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Comments
Ldl lowering has little impact on mortality by CAD
Huge volume 1.3 lakhs of patients form sampling across many studies in assessing the impact of lowering the LDL on mortality due to CAD. And the neet benefit was found to be very minimal.
LDL lowering of minimal benefit?
This seems to be counterintuitive to the 50% reducton in vascular mortality seen over my four decades in practice. I have always worked to control hypertension, T2DM and lipids in my patients to target. Is the LDL component of my efforts not at least partly responsible for the benefits I see? This study would suggest so.
Statins
Yes!!! I knew it. And they still want me to put my 90 year olds on this stuff.
LDL lowering with statins.
I'm quite relieved to hear this as I find it difficult to start patients on statins when their HDL and triglycerides are exemplary, yet their LDL's a little high. Now I can discuss it with them with more information.
Stains and LDL lowering
Without knowing the degree of lowering, i.e. the LDL target numbers, the info does not assist.
LDL
Unlikely this will deter the pundits from pushing statins when they are not appropriate!
Treating LDL to target of little benefit to patients a
This is another piece of evidence to move away from treating according to guidelines in primary prevention interventions by using Risk Stratifications.
lowering ldl post mi
minimal reduction in recurrent mi's etc??