STAREE Strengthens Case for OTC Statins

John M. Mandrola, MDThe primary prevention STAREE trial of atorvastatin 40 mg in older adults has delivered positive results. Our job as clinicians is to share the findings with patients and let them decide if they want the drug. Statins are the most studied therapy in modern medicine. Their approximate 25% relative risk reduction in nonfatal cardiac events has been confirmed in trials of low- and higher-risk patients. Until STAREE, we did not know whether this benefit applied to older adults. The STAREE Trial Nearly 10,000 patients were recruited from general medicine clinics in Australia in what was a true primary prevention trial because any cardiovascular disease was an exclusion criteria. The mean age of patients was 75 years (nearly 40% were older) and half were female. The average baseline lipid numbers were hardly that terrible: low-density lipoprotein cholesterol (LDL-C), 126 mg/dL; high-density lipoprotein cholesterol, 62 mg/dL; and triglycerides, 113 mg/dL. There were two primary endpoints: a major adverse cardiac event composite endpoint of myocardial infarction (MI), stroke, coronary revascularization and cardiovascular death, and a disability-free survival endpoint of all-cause death, dementia, and persistent physical disability. Results Adherence to the study medication was poor. After 5 years, 45% of individuals in the statin arm and 53% of individuals in the placebo arm were not taking the study drug. Open-label statin use was reported in 19% of patients in the placebo arm by year 5. In the atorvastatin arm, LDL-C dropped 35 mg/dL more, on average, than placebo. Over nearly 6 years, a primary endpoint occurred at a rate of 10.9 per 1000 person-years in the statin arm vs 15.5 per 1000 person-years in the placebo arm (hazard ratio [HR], 0.70; 95% CI, 0.61-0.82; P < .001). The drivers of the lower rate were MI, stroke, and revascularization. Rates of both all-cause and cardiovascular death were similar in both arms. The second composite primary endpoint of death, dementia, or persistent physical disability was 6% lower in the statin arm but did not differ statistically (HR, 0.94; 95% CI, 0.84-1.05; P = .25). Rates of dementia were almost identical. Persistent physical disability rates were very low and also similar (2.2 vs 2.9 per 1000 patient-years). “Medically important adverse events” occurred in 8.8% of patients in the statin arm vs 6.7% in the placebo arm. Musculoskeletal and connective tissue disorders (32% vs 29.4%) and hepatobiliary disorders (3.3% vs 0.9%) were both slightly higher in the statin arm. Conclusion The interpretation of this well-conducted trial is simple: in this older but seemingly healthy population, atorvastatin reduces the risk for nonfatal cardiac events but does not extend lifespan or lower dementia and physical disability. Adverse effects overall were neither worrisome nor much different from previous statin trials. The absolute risk reduction was small. The authors report a number needed to treat (NNT) to prevent one major adverse cardiovascular event as 37, but that is over nearly 6 years. The NNT per year is more than 200. I am not surprised by the results because statins have shown remarkably consistent results in both primary and secondary prevention trials. The 30% relative risk reduction in STAREE is consistent with the known benefits of statins. Some may posit a larger risk reduction with better adherence. This is a mistake because statin adherence is what it is. The crossover to open-label statin use is also not unexpected because surely patients who have events were started on statins. One caution about translating this data in the clinic is that patients with serious disability or frailty were not included. I would not assume this effect applies to patients with substantial comorbidity. Notable also is that only 4% of individuals in the trial were older than 85. STAREE reinforces my long-held view that doctors need hardly be involved in statin decision-making. These drugs should be over the counter where patients can decide with their own money if they want to take more than 2000 tablets over 6 years to reduce cardiac events by a few percent. People take supplements to improve their health with nowhere close to this level of evidence. They could consider atorvastatin a well-studied heart supplement. In STAREE, the small absolute risk reduction in MI, stroke, and coronary revascularization was not large enough to improve survival or lead to less overall disability. Older people have different preferences. Maximizers will take the pill; minimizers will not. I laud the Australian team for providing evidence where there was little. Older adults similar to those enrolled in this trial can now make an informed decision about statin use. I am happy to help, but it’s 100% their choice. The data are so clear that my opinion is hardly more relevant than theirs. John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence.