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Not Getting to LDL-C “Goal” Provides Best Mortality and Risk Benefit
DuBroff R, Malhotra A, de Lorgeril M. Hit or miss: the new cholesterol targets [published online ahead of print, 2020 Aug 3]. BMJ Evid Based Med. 2020;bmjebm-2020-111413. doi:10.1136/bmjebm-2020-111413. PMID: 32747335
This best evidence review of 35 clinical trials aimed to determine if the use of medications (statins, PCSK9 inhibitors, ezetimibe) to lower LDL-C to targets outlined by the 2019 AHA/ACC guidelines was effective in altering the course of cardiovascular outcomes like myocardial infarction or death.
2018 AHA/ACC guidelines:
• “Moderate risk” defined as aged 40–75 with diabetes and LDL-C between 70 and 189mg/dL, or aged 40–75 without atherosclerotic cardiovascular disease (ASCVD) or diabetes and LDL-C between 70 and 189mg/dL with 10-year ASCVD risk ≥7.5% -20%; the LDL-C goal should be a 30% reduction
• “High risk” defined as anyone with known clinical ASCVD (secondary prevention) or an LDL-C ≥190mg/dL, or those aged 40–75 without ASCVD or diabetes with LDL-C between 70 and 189mg/dL and 10-year ASCVD risk ≥20%; LDL-C goal of >50% reduction
In the 13 RCTs where the LDL-C reduction targets were achieved, only one reported a mortality benefit and five reported a reduction in cardiovascular events.
But, in the 22 RCTs where the LDL-C reduction targets were NOT achieved, four reported a mortality benefit and 14 reported a reduction in cardiovascular events.
The beneficial effect in cardiovascular events was seen with low LDL-C reductions as little as 11%–15%, and a far lesser benefit was seen with LDL-C reductions of 50% or more.
The number needed to treat to prevent death was 30 patients treated with simvastatin for 5.4 years (4S study [Lancet 1994;344:1383–9]; LCL-C reduction of 35%) but was 250 patients on alirocumab (PCSK9 inhibitor) for 2.8 years (Odyssey Outcome trial [N Engl J Med 2018;379:2097–107]; LDL-C reduction of 55%).
Cardiovascular outcomes had small benefit from aggressive (>50%) LDL-C reduction, with best reduction in myocardial events and mortality with LDL-C lowering of 11-15%.
The Number Needed to Treat is defined as the number of patients given an intervention, over a designated time, to achieve one additional benefit from that intervention. This statistic is frequently a board question. The calculation is NNT = 100/Absolute Risk Reduction.
Example: in a randomized, controlled trial, Drug X and placebo were given to patients over 5 years to prevent a stroke in patients with atrial fibrillation. At 5 years, the rate of stroke was 2% in the intervention (Drug X) group vs. 12% in the placebo group. The NNT = 100/[12% - 2% or 10%] or 100/10 = 10; thus 10 patients would need to be treated with Drug X for 5 years to prevent one additional stroke.
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Contributed by Frank J. Domino, MD, March 3, 2021