How do statin-associated NNTs vary by baseline risk, age, and LDL-C levels in secondary prevention trials?

1. Why baseline risk drives NNT: the math reporters use

NNT is a function of absolute risk reduction, which equals baseline risk × relative risk reduction; statin trials generally find similar proportional relative effects across risk strata, so higher baseline event rates produce much lower NNTs. Meta-analyses and practical calculators show that at 10–year risks of 20–40% the extrapolated NNT can be in single digits or low teens, whereas at low baseline risks the 5‑year NNTs commonly exceed 100–200 (bandolier simulations and guideline examples) ^{[4] [5]}.

2. What secondary‑prevention trials and reviews report about NNTs

Secondary‑prevention cohorts have high absolute event rates, so NNTs are favorable. Reappraisal of trials found placebo‑group baseline risks ranging from ~2.5% to >16%, permitting extrapolated 10‑year NNT comparisons across studies ^[6]. Guideline reviews that synthesize those RCTs note consistent proportional risk reductions per 1 mmol/L LDL‑C (~22% reduction in ASCVD) and recommend aggressive LDL‑C lowering in secondary prevention because the absolute benefit (and thus low NNT) is large when baseline risk is high ^{[7] [2]}.

3. Age and subgroup effects: younger vs older secondary‑prevention patients

Sources report that the magnitude of relative benefit per unit LDL‑C fall is broadly consistent and may even be greater in younger patients; however, absolute gains — and therefore NNTs — depend on competing mortality and remaining life‑years. The Endotext review states a ~22% ASCVD risk reduction per 39 mg/dL (1 mmol/L) LDL‑C fall and notes that lifelong LDL‑C exposure matters, implying younger patients with longer life expectancy may accrue greater lifetime absolute benefit and lower lifetime NNTs if treated early ^[7]. Available sources do not provide a single age‑stratified NNT table for secondary prevention but indicate younger age amplifies lifetime benefit ^[7].

4. LDL‑C level (baseline and on‑treatment) changes the NNT materially

Trials and reviews show proportional benefits per mmol/L LDL‑C reduction; therefore, patients with higher baseline LDL‑C or who achieve greater LDL‑C drops (via high‑intensity statin ± add‑ons) realize larger absolute risk reductions and lower NNTs. Evidence syntheses emphasise that more intensive regimens (on average ~20 mg/dL extra LDL‑C drop in trials of intensive vs less‑intensive statins) translated into ~15% further reduction in major vascular events — lowering NNTs accordingly ^{[8] [2]}. The literature also stresses on‑treatment LDL‑C as highly predictive of residual risk, with lower achieved LDL‑C associated with incrementally lower event rates ^[9].

5. Examples from trials and cohorts — concrete NNT ranges

Randomized secondary‑prevention contrasts and subgroup RCT data yield low NNTs: JUPITER (primary prevention population but useful for subgroup comparisons) reported 5‑year NNTs as low as 17 for men and 31 for women in certain subgroups, illustrating how sex, baseline risk markers, or biomarker selection alter NNTs ^[1]. Observational cohort analyses and guideline projections show 5‑year NNTs of ~62 in the 10–19.9% risk group and much higher NNTs (e.g., 470) in <5% risk strata — again underscoring baseline risk effects ^[10].

6. Nuance, limitations, and competing viewpoints

Authors and guideline panels agree on consistent proportional benefit per LDL‑C reduction, but differ in emphasis: some analyses and guideline thresholds focus on absolute‑risk thresholds to decide who merits therapy, while other approaches (causal‑benefit or treat‑to‑LDL targets) stress baseline LDL‑C and magnitude/timing of LDL‑C lowering ^{[6] [11]}. Observational real‑world data highlight implementation gaps — many secondary‑prevention patients do not reach LDL targets, which raises realized NNTs in practice compared with ideal trial conditions ^{[12] [13]}. Available sources do not provide a single unified matrix of NNT by exact age, baseline risk, and baseline LDL‑C for secondary prevention; instead, they present consistent principles and multiple illustrative NNTs from trials and cohorts ^{[6] [7] [9]}.

7. Practical takeaway for clinicians and patients

In secondary prevention, expect low NNTs (good absolute benefit) when baseline event rates are high and when therapy achieves substantial LDL‑C reductions; use achieved LDL‑C and absolute baseline risk to estimate benefit. Guideline and trial evidence supports early, intensive LDL‑C lowering (≥50% reduction goal in secondary prevention) to minimize NNT and prevent recurrent events ^{[7] [2]}.