By Michael H. Crawford, MD, Editor

SOURCE: Yeboah J, et al. Implications of the new American College of Cardiology/American Heart Association cholesterol guidelines for primary atherosclerotic cardiovascular disease event prevention in a multi ethnic cohort: Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J 2015;169:387-395.

The American College of Cardiology/American Heart Association (ACC/AHA) released new guidelines for the use of statin drugs to prevent atherosclerotic cardiovascular disease (CVD) in 2013. Because these guidelines increase the number of apparently healthy people who are eligible for stain therapy, there is concern among practitioners that the potential adverse effects of statins may outweigh the imputed benefits. Since any randomized trial to test this hypothesis is years away from completion, these investigators analyzed the Multi Ethnic Study of Atherosclerosis (MESA) database to assess the impact of the new guidelines on the number of patients eligible for statin therapy. Also, using randomized trial data for statin therapy, they analyzed primary prevention statin trials to estimate the reduction in CVD risk for these patients and the risk of adverse effects of using moderate- or high-intensity statins. MESA subjects aged 40-75 years at baseline enrollment who were not on a statin were selected, which resulted in a population of 5437; mean age was 61 years.

Using the 2001 National Cholesterol Education Program/adult treatment panel III (NCEP/ATP III) guidelines, 25% of these patients would have been eligible for statin therapy. This increased to 56% under the new guidelines and 66% if the optional category was added. Only 5% who were eligible under the old guidelines were no longer eligible under the new guidelines. Among the newly eligible 1742 patients, 127 (7%) had a CVD event during 10 years of follow-up. If you assume 10 years of moderate statin therapy, the absolute reduction in events would be 2%, number needed to treat (NNT) 49, the absolute increase in diabetes would be 0.9%, and the number needed to harm (NNH) 111. If high-intensity statins were chosen, the absolute reduction would be 3% (NNT 38), with a diabetes increase of 3% (NNH 39). Under the old guidelines, the reduction in events would be 3% (NNT 32) and new diabetes 1% (NNH 94). The incidence of rhabdomyolysis estimated to occur in the MESA cohort with the new guidelines is < 1%. The authors concluded that under the new statin treatment for primary prevention guidelines, the risk:benefit ratio is much better for moderate- than high-intensity statins.

COMMENTARY

The lack of supportive data for the new guidelines and the estimation that more subjects will be eligible for statin therapy, which is often a tough sell in asymptomatic individuals, has led to reluctance on some practitioners’ part to embrace these guidelines. Thus, the data presented in this analysis of the MESA database and recent primary prevention statin trials are informative.

As predicted, the number of patients eligible for statin therapy doubled. Based on statin primary prevention trial data, with moderate-intensity statin therapy, CVD events would decrease and new diabetes rates would increase. With high-intensity statin use, CVD events would decrease more but diabetes rates would be higher; rhabdomyolysis rates would be negligible. Other adverse events were not studied such as cognitive impairment, liver abnormalities, and muscle aches. Thus, under the new guidelines, those with a predicted 10 event rate of > 7.5% should be treated with moderate-intensity statins.

These estimates assume high statin compliance, but the literature suggests it is 50-65% in primary prevention patients. Most patients stop statins because of muscle aches and liver function test abnormalities, even though routine liver blood tests are no longer recommended in asymptomatic patients. These side effects were not studied, and the rate of statin discontinuation is not known in this study. If the adherence rate were lower, then the assumed overall benefit would be reduced, but so would the incidence of diabetes.

The strengths of this study are the large size of the MESA database, the knowledge of 10-year event rates, and the multiethnic make-up of the population. Weaknesses include that MESA is an observational community-based study and the statin trials are a more select group of patients that may not be comparable. Also, MESA doesn’t include all the ethnicities seen in the United States, but comes closer than most studies. One difference between the new guidelines and the old is that the old guidelines were based on hard endpoints only (death and myocardial infarction). The cutoff for considering statin therapy was a predicted 10-year incidence of hard endpoints of > 20%. The new guidelines include stroke, which is perhaps more relevant since trials have shown reduced stroke rates in some patient groups with statins, and uses a 10-year incidence cutoff of > 7.5%. This design fact alone increases the number of patients in whom statin therapy should be considered. Although this analysis supports the conclusions of the new guidelines, only prospective, randomized trials will confirm this approach.