STAREE: Atorvastatin Cut CV Events, Not Disability-Free Survival

Key Takeaways

• Among community-dwelling adults aged at least 70 years in Australian general practices, with no prior cardiovascular disease, diabetes, or dementia, atorvastatin 40 mg daily lowered the hazard of a first major cardiovascular event by about 30% compared with placebo (hazard ratio 0.70; 95% CI, 0.61–0.82).
• The composite of death from any cause, dementia, or persistent physical disability did not differ significantly between groups (hazard ratio 0.94; 95% CI, 0.84–1.05).
• Musculoskeletal, hepatobiliary, and diabetes-related adverse events were more frequent with atorvastatin, while serious adverse events were balanced at 2.7% in both groups.

For older adults considering a statin before a first cardiovascular event, preventing cardiovascular disease and preserving independence are related but distinct goals. The STAREE trial tested atorvastatin against placebo on both.

In this double-blind, randomized, placebo-controlled trial, run in general medical practices across Australia, investigators assigned 9,971 community-dwelling adults 1:1 to atorvastatin 40 mg once daily (4,984 participants) or identical placebo (4,987). Participants had a mean age of 74.7 years, and 51.9% were women. Median follow-up was 5.9 years.

The trial had two primary endpoints. The first, major cardiovascular events, was a composite of cardiovascular death, nonfatal myocardial infarction or stroke, or coronary revascularization. The second was a composite of death from any cause, dementia, or persistent physical disability, intended to assess disability-free survival.

A primary cardiovascular event occurred in 297 participants taking atorvastatin (10.9 per 1,000 person-years) and 412 taking placebo (15.5 per 1,000 person-years), for a hazard ratio of 0.70 (95% CI, 0.61–0.82; P<0.001). That corresponds to 6.0% of participants with atorvastatin versus 8.3% with placebo. The reduction was predominantly in nonfatal events.

The disability-free survival composite occurred in 637 participants taking atorvastatin (21.6 per 1,000 person-years; 12.8%) and 676 taking placebo (23.0 per 1,000 person-years; 13.6%). The hazard ratio was 0.94 (95% CI, 0.84–1.05; P=0.25), not a statistically significant difference. Musculoskeletal, hepatobiliary, and diabetes-related adverse events were more common with atorvastatin. Serious adverse events were uncommon and balanced, occurring in 131 participants (2.7%) taking atorvastatin and 129 (2.7%) taking placebo.

The nonsignificant result for the disability-free survival composite does not show that atorvastatin has no effect on that outcome. Because the composite combines death, dementia, and persistent physical disability, the trial’s reported result does not isolate an effect on any one component. The trial enrolled adults without cardiovascular disease, diabetes, or dementia in Australian general practices, so it provides no direct evidence for people with those conditions or in other settings. The STAREE investigators concluded that atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival.