Does statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) therapy reduce the risk of cardiovascular events, such as heart attacks and stroke, but not necessarily overall mortality in patients at risk of cardiovascular disease?

Statins Reduce Cardiovascular Events But Also Reduce Mortality

Contrary to the premise of your question, statin therapy does reduce both cardiovascular events AND overall mortality in appropriate patient populations. The evidence clearly demonstrates mortality benefits, particularly in secondary prevention and high-risk primary prevention settings.

Evidence for Mortality Reduction

Statin therapy significantly reduces all-cause mortality by approximately 14% (RR 0.86,95% CI 0.80-0.93) and cardiovascular mortality by 31% (RR 0.69,95% CI 0.54-0.88) in primary prevention populations. 1 This represents an absolute risk reduction of 0.40% for all-cause mortality over trial durations averaging 2-5 years. 1

A more recent 2025 meta-analysis of over 500,000 patients confirmed these findings, showing a 40% reduction in all-cause mortality (RR 0.60,95% CI 0.43-0.83) with statin therapy. 2 The magnitude of benefit varies based on baseline cardiovascular risk—higher-risk patients derive greater absolute mortality benefits even though relative risk reductions remain consistent across risk strata. 1

Cardiovascular Event Reduction

Beyond mortality, statins produce robust reductions in cardiovascular events:

• Myocardial infarction risk decreases by 36% (RR 0.64,95% CI 0.57-0.71), with an absolute risk reduction of 0.81%. 1
• Stroke risk decreases by 29% (RR 0.71,95% CI 0.62-0.82), with an absolute risk reduction of 0.38%. 1
• Composite cardiovascular outcomes decrease by 30% (RR 0.70,95% CI 0.63-0.78), with an absolute risk reduction of 1.39%. 1
• Each 39 mg/dL reduction in LDL cholesterol produces a 21% reduction in major vascular events, including a 24% stroke reduction even in patients with estimated 5-year cardiovascular risk <10%. 3

Secondary Prevention: Enhanced Mortality Benefits

In secondary prevention (patients with established cardiovascular disease), mortality benefits are even more pronounced. The SPARCL trial demonstrated that high-dose atorvastatin 80 mg reduced major cardiovascular events by 20% (HR 0.80,95% CI 0.69-0.92) in stroke patients. 3

For acute coronary syndrome patients specifically, intensive statin dosing reduces all-cause mortality by 25% (RR 0.75,95% CI 0.61-0.91) and cardiovascular mortality by 26% (RR 0.74,95% CI 0.59-0.94). 4 The TNT trial showed that atorvastatin 80 mg versus 10 mg reduced major cardiovascular events by 22% (HR 0.78,95% CI 0.69-0.89) in patients with established coronary disease. 5

Why the Misconception Exists

The confusion likely stems from individual trials being underpowered to detect mortality differences, particularly in lower-risk primary prevention populations where absolute event rates are small. For example, the SPARCL trial showed no statistically significant difference in death rates (p=0.98) when analyzed alone, despite clear reductions in cardiovascular events. 3 However, meta-analyses pooling multiple trials consistently demonstrate mortality benefits. 1, 2

Additionally, some trials show non-significant trends toward cardiovascular mortality reduction when analyzed individually (RR 0.74,95% CI 0.53-1.02), but these become statistically significant when pooled with adequate sample sizes. 2

Clinical Algorithm for Statin Therapy

For primary prevention:

• Initiate statins in adults aged 40-75 years with ≥1 cardiovascular risk factor (dyslipidemia, diabetes, hypertension, smoking) and 10-year cardiovascular risk ≥10%. 3
• Consider statins for 10-year risk 7.5-10% after shared decision-making. 3
• Target LDL-C <70 mg/dL for patients with atherosclerotic disease. 3, 6

For secondary prevention:

• All patients with ischemic stroke, TIA, or established coronary disease should receive high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20-40 mg). 3, 6, 7
• Target LDL-C <70 mg/dL or ≥50% reduction from baseline. 6, 8

Safety Considerations

Serious adverse events are rare: rhabdomyolysis occurs in <0.1% of patients, serious hepatotoxicity in ≈0.001%, and new-onset diabetes in ≈0.2% per year. 9 The risk-benefit ratio strongly favors statin use in guideline-recommended populations, as the absolute benefits in preventing death and cardiovascular events far exceed these small risks. 9, 1

One notable exception: patients with prior hemorrhagic stroke have increased risk of recurrent hemorrhagic stroke with statins (HR 5.65,95% CI 2.82-11.30), though overall stroke risk still decreases due to larger reductions in ischemic events. 6, 8