Twice as Deadly? Statin Drug Crestor Associated with Over Double the Mortality Rate in ARDS Trial

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When it comes to cholesterol levels and statin medications, less is not always more. Drastically low cholesterol may deprive patients of crucial biological functions during acute critical illness, while some statins like rosuvastatin appear to further endanger these already vulnerable individuals

This secondary analysis of two large acute respiratory distress syndrome (ARDS) trials delivers an important warning: low cholesterol bears a relationship with poorer outcomes, and we must rethink blanket statin recommendations without considering individual lipid profiles.

The SAILS trial found the lowest baseline cholesterol quartile (<69mg/dL) correlated with significantly higher prevalence of shock and severity scores. Most strikingly, the 37.8% of these patients randomized to rosuvastatin (aka Crestor) died by 60 days, over twice the rate of the placebo group (OR 2.23).1

Meanwhile in HARP-2, the lowest quartile (<44mg/dL) had markedly higher illness severity. Yet among this high-risk cohort, a non-significant 31.9% mortality rate emerged for simvastatin versus 52.1% for placebo.2

How do we explain this discrepancy? Why would the same subset experience harm from rosuvastatin yet potential protection by simvastatin? The differing potencies, lipophilic properties, antimicrobial effects, and off-target interactions of these two statins may hold clues.

Regardless of the mechanism, these results underscore the risks of aggressive cholesterol reduction in those already depleted. As the authors note, cholesterol plays vital roles in ARDS through surfactant production,3 binding and neutralizing inflammatory endotoxins,4 and transporting antioxidant vitamin E into alveoli.5

Stripping away these protective functions leaves patients exceptionally vulnerable. We witness this clearly with rosuvastatin exaggerating mortality in the lowest baseline cholesterol cohort.

Yet mainstream medicine continues pushing for lower numeric targets, with implications far beyond this ARDS population. Accelerating statin use, even enshrining it in clinical guidelines, seldom accounts for the complex interindividual differences on display here.6

In fact, over 300 adverse effects have been linked to statins according to the research portal GreenMedInfo, ranging from neurodegeneration to Mitochondrial DNA damage.7 A wise clinician would weigh the evidence on both sides before intensifying cholesterol reduction attempts in already replete patients.

For too long we have conflated numerical metrics with therapeutic benefit across healthcare. But patients are more than LDL numbers. Their unique constitutions and susceptibilities, so salient during acute crises, must guide decision making above all. This study spotlights the inconsistencies and unintended consequences that emerge when we practice otherwise.

To learn more about the dangers of low cholesterol read our previous article: How Low Cholesterol Can Damage Your Health.

For alternative, evidence-based strategies to lower cholesterol naturally, visit our extensive database covering over 150 natural substances here.


1. Pienkos et al., Critical Care (2023)

2. Pienkos et al., Critical Care (2023)

3. Karlson et al., Eur J Prev Cardiol (2016)

4. Meor Anuar Shuhaili et al., Int J Endocrinol Metab (2017)

5. Masadeh et al., Ann Clin Microbiol Antimicrob (2012)

6. Pian & Dobbs, Am J Physiol (1997)

7. Levels et al., Crit Care Med (2003)

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