Suboptimal statin response linked to worse cardiovascular disease risk


By Will Boggs MD

NEW YORK (Reuters Health) - The risk of cardiovascular disease is increased in patients who have a suboptimal LDL cholesterol response to statin therapy, researchers from UK report.

"What we found most surprising is the magnitude of individuals prescribed statins for primary prevention of cardiovascular disease (over 50%) not achieving targeted reductions in LDL cholesterol," Dr. Stephen F. Weng from University of Nottingham, Nottingham, UK told Reuters Health by email. "That means, as our study determined, these individuals are not getting the optimal preventive benefits of being on statins for preventing heart disease and strokes."

For patients with hypercholesterolemia, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend LDL cholesterol reductions of 30-49% for moderate intensity statins and at least 50% for high intensity statins. The National Institute for Health and Care Excellence (NICE) guidelines in the UK aim for >40% reduction in non-HDL cholesterol.

Dr. Weng's team used linked data from the UK Clinical Practice Research Datalink, Hospital Episode Statistics, and National Statistics to assess differences in LDL cholesterol response in primary care patients initiated on statins and their impact on future cardiovascular disease (CVD) risk.

Among the 165,411 patients included in the study, 84,609 (51.2%) had a suboptimal LDL cholesterol response 24 months after initiating statin therapy, according to the April 15th online report in Heart.

The rate of CVD was 22.6 per 1000 person-years for suboptimal responders and 19.7 per 1000 person-years for optimal responders.

After adjusting for age and baseline LDL cholesterol, the risk of CVD was 22% higher in suboptimal responders than in optimal responders.

In adjusted models, suboptimal responders had significantly increased risks of each of the constituent CVD outcomes (coronary artery disease, stroke/TIA, peripheral vascular disease, and cardiovascular disease-related death).

Each 1-mmol/L (about 39 mg/dL) reduction in LDL cholesterol was associated with a 6% decrease in any CVD among patients with suboptimal decreases in LDL cholesterol but with a 13% decrease in any CVD among patients with optimal responses.

Recent changes to clinical guidelines for prescribing (AHA/ACC in the US and NICE in the UK) are likely to increase prescribing up to 56 million adults in the US and 12 million adults in the UK, Dr. Weng said. He added, "That means the magnitude of poor cholesterol response to statins is likely also to increase. The implications of the findings suggest that we need to think very carefully about how to improve effective implementation of the guidelines and develop cost-effective ways and tools (for instance, through the use of technology) where we can support health care practitioners in improving monitoring and medication switching due to side effects. This will also have benefits in helping patients for improving adherence to treatment."

"In individuals who do achieve the targeted reductions in LDL cholesterol, there was a confirmed protective effect from statins for cardiovascular diseases, which has been demonstrated from many clinical trials," he said. "The key here is we need to get better at converting those who do not achieve these targeted reductions to individuals who do, so they can gain these important protective effects."

Dr. Marcio S. Bittencourt from University Hospital, Sao Paulo, Brazil, who co-authored an editorial related to this report, told Reuters Health by email, "The reasons for the inability to reach adequate LDL cholesterol reduction in real setting are likely to be multifactorial. We believe this is related to both physician and patient behavioral aspects in the vast majority of cases. While physicians may prescribe lower than ideal levels of statins, patients might not fully adhere to the prescribed treatment. Although no detailed data on the reasons for not reaching target LDL cholesterol levels is presented, we believe statins under-response is unlikely to play a major role."

"Physicians should not only prescribe statins, but should do so with a statin dose likely to reach guideline recommended levels," he said. "Physicians should also consider additional therapy, such as ezetimibe, in cases where the highest tolerated dose is unable to lower LDL cholesterol to the recommended levels."

"Moreover, physicians need to understand that time and effort should be spent on patient education on the need for statin treatment for cardiovascular risk reduction, including behavioral and support interventions, in order to improve patients' adherence to medication and non-pharmacological treatment strategies," Dr. Bittencourt said.


Heart 2019.

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