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Overuse alert: treat-to-target LDL strategy of statin dosing is noninferior to high-intensity dosing
Clinical Question
Is a strategy of treat-to-target statin dosing noninferior to high-intensity dosing for adults with coronary artery disease?
Bottom line
This study found that statin dosing based on a treat-to-target LDL level of 50 mg/dL to 70 mg/dL is noninferior to a high-intensity strategy for reducing adverse events in adults with established CAD. Although the authors see this as an advantage that allows a tailored approach for individual dosing variability, it also serves as some of the best evidence yet that we can manage our patients with a high-intensity strategy and avoid the costs and burdens of repeated LDL testing. 1b
Reference
Study design: Randomized controlled trial (single-blinded)
Funding: Industry
Setting: Outpatient (any)
Synopsis
There is minimal evidence supporting the superiority or noninferiority of a high-intensity strategy of statin dosing versus a strategy of treating to a target low-density lipoprotein (LDL) level. These investigators identified 4400 adults with coronary artery disease (CAD), including both stable ischemic heart disease and acute coronary syndrome. Eligible patients randomly received (concealed allocation assignment) a statin using either a strategy of treat-to-target an LDL level between 50 mg/dL and 70 mg/dL, or a strategy of high-intensity therapy (20 mg rosuvastatin or 40 mg atorvastatin daily) without dose adjustment based on follow-up LDL levels. An independent committee masked to treatment group assignment assessed outcomes. Complete follow-up occurred for 98.7% of participants at 3 years. Using both intention-to-treat and per-protocol analysis, the primary endpoint (a composite of all-cause death, myocardial infarction, stroke, and any coronary revascularization) occurred in 8.1% of the treat-to-target group and 8.7% in the high-intensity statin therapy group (nonsignificant difference; meeting the significance for noninferiority). No significant group differences occurred for multiple prespecified secondary end points, including new-onset diabetes, elevated liver enzymes, hospitalizations, end-stage kidney disease, or study drug discontinuation due to intolerance.
Reviewer
David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC
Comments
Impact assessment
Excellent
Info Poems
Please keep info poems CMA! It's your best feature :)
LDL target
Cardiologists routinely target LDL levels, so unless this changes, no change will occur at the primary care level.
What is considered high dose statin?
I would consider crestor 40mg and lipitor 80mg as high dose statins. I wonder if the results would be different if they used those does in the comparator arm.
Whack EM with max dose?
Why not? Then no LDL testing. What a biased commentary
I have a different take…
Their conclusion is such that it is ‘non-inferior’ to use high dose, but my conclusion is that it is non-inferior to not be as aggressive.
cost
I think the long term costs of high intensity treatment are likely higher than testing til get to target and then stop testing.
SI Units
It would useful to have the SI units in brackets after the numbers quoted.
Treat to Target LDL strategy
The evidence based medicine group at University of Alberta and the Tools for Practice of the Alberta College of Family Physicians have long shown that LDL (indeed all lipids) are surrogate markers. Once someone is on a statin there is no need to monitor lipid levels. The use of using cholesterol targets for reducing CVD is not required. See the Clinical Practice Guideline as published in the Canadian Family Physician.
dosing
It is misleading to say that this study used "high dose " statin when it did not. High dose is crestor 40 or lipitor 80mg as a previous colleague indicated and I would add, that ezetrol, vascepa, and even Repatha can be added to make it truly High dose lipid management.
Further, the Repatha studies have presented the concept of lowering Lipoprotein A with Repatha, something that is not as possible with the statins. When you consider the overall health implications of CVS disease in our population, I feel that we still need to do more.
lipid treatment
target ok