Although patients with recent acute coronary syndrome derive added benefit from higher-dose statin therapy, patients with stable symptoms may not get a net additional benefit from higher doses, according to an article in the May 8 issue of Circulation.

Studies that have compared high and standard doses of statins have shown significant differences in the risk of negative events among patients taking higher doses. And that has helped lead to the current recommendations by the federal National Cholesterol Education Program and others, which call for aggressive statin treatment.

But, the team noted that results from these studies are often expressed in terms of composite end points - for instance, the risk of death, heart attack and stroke put together, rather than the risk of each. That practice yields the most dramatic differences between high-dose and standard-dose statin treatment, but it masks the fact that there may not have been significant differences between the two groups in some of those individual events (death, myocardial infarction, or stroke). It also assumes that each of these events is viewed equally by doctors and patients, which is clearly not the case.

For the current study, the researchers pooled clinical trial data from all patients with a history of acute coronary syndrome, and in a separate pool, all patients with coronary artery disease. They looked at all differences between high-dose and standard-dose patients in those pools, including their risk of cardiovascular events during the study period. They then used the information to create a computer model of hypothetical 60-year-old adults taking different doses of statins, and calculated what reduction in risk might be related to those doses, any how many “quality-adjusted life years” they might gain from that reduction in risk.

“Clinical trials have effectively demonstrated that high-dose statins reduce cardiovascular endpoints in patients with established coronary artery disease. However, we found that whereas high-dose statin therapy reduced mortality in patients with acute coronary syndromes, patients with stable coronary artery disease had no mortality benefit from high-dose statins, but only reductions in stroke and repeat heart attack risk,” said Paul Chan, MD, MSc, the study’s lead author and a fellow in cardiovascular medicine at the U-M Medical School.

“Our study illustrates that simply having a ‘positive’ clinical trial may not be as informative as reporting what the actual gains in life expectancy and quality of life are with positive trials, and we propose using decision analysis as a way to appreciate the impact of trials that use multiple end points that are dissimilar (e.g., death and rehospitalization),” said Chan, who is also a member of the VA Health Services Research and Development Center of Excellence at VA Ann Arbor.

Sandeep Vijan, MD, senior author, added, “In this study, we found that intensive treatment with statins, a treatment with ‘proven’ effectiveness, has very different effects depending on who you are. If you are a very high-risk patient who was just in the hospital for a heart attack, you get lots of benefit from high doses of statins, and treatment is therefore cost-effective.”

“This is further compounded by the fact that the higher-dose treatments are less well-tolerated, and my clinical experience is that once patients decide the drugs are hard to tolerate, they often won’t even take the lower dose drugs, which are enormously beneficial,” Vijan added.

The team based its analysis on data from four very large clinical trials - those whose results led to recommendations of higher doses of statins for patients with acute coronary syndrome or coronary artery disease. They combined those data with data on cost and a range of estimates about how long the drug’ beneficial effect would last.