https://immattersacp.org/weekly/archives/2019/04/23/1.htm

More than half of people taking statins may have suboptimal improvement in LDL cholesterol

There was a significantly increased risk of coronary artery disease, peripheral vascular disease, and cardiovascular disease-related death in patients with a suboptimal response to statins compared with those with an optimal response.


Optimal cholesterol lowering was not achieved in more than half of statin users within two years, and these patients will experience significantly increased risk of future cardiovascular disease (CVD), a study concluded.

To assess LDL cholesterol response after initiation of statins and future risk of CVD, British researchers conducted a prospective cohort study of 165,411 primary care patients derived from a U.K. primary care database. All were free of CVD before starting a statin. Based on U.K. guidelines, a less than 40% reduction in baseline LDL cholesterol within 24 months was classified as a suboptimal response. Results were published by Heart on April 15.

Overall, 51.2% of patients had a suboptimal response to statin therapy within 24 months. During 1,077,299 person-years of follow-up (median follow-up, 6.2 years), there were 22,798 CVD events (12,142 in suboptimal responders and 10,656 in optimal responders). CVD event rates were 22.6 and 19.7 per 1,000 person-years for suboptimal and optimal responders, respectively.

Patients with a suboptimal response were significantly more likely to have an incident CVD event (crude hazard ratio [HR], 1.17; 95% CI, 1.13 to 1.20; P<0.001). After adjustment for age and baseline untreated LDL cholesterol, the risk of CVD remained significantly greater in suboptimal responders compared with optimal responders (adjusted HR, 1.22; 95% CI, 1.19 to 1.25; P<0.001). A competing risk approach found a lower but similar CVD risk for suboptimal response with both unadjusted (HR, 1.13; 95% CI, 1.10 to 1.16; P<0.001) and adjusted (HR, 1.19; 95% CI, 1.16 to 1.23; P<0.001) analyses.

There was a significantly increased risk of coronary artery disease, peripheral vascular disease, and CVD-related death in patients with a suboptimal response versus those with an optimal response. Adjusted models showed an increased risk that remained significant for all outcomes, including stroke and transient ischemic attack.

Among patients who had any reduction in LDL cholesterol within 24 months (n=146,355), 65,862 (45%) had a suboptimal response. A unit reduction of 1 mmol/L (39 mg/dL) was found to be associated with a significant decrease in CVD risk (odds ratio [OR], 0.94; 95% CI, 0.91 to 0.98) even in patients with suboptimal decreases in LDL. Patients with an optimal response saw an even greater protective effect (OR, 0.87; 95% CI, 0.84 to 0.90).

Statins rank among the most commonly prescribed drug classes, the authors noted, and revised clinical guidelines for CVD risk reduction have significantly expanded the population of patients deemed eligible for statin therapy.

“Currently, there is no management strategy in clinical practice which takes into account patient variations in LDL [cholesterol] response, and no guidelines for predictive screening before commencement of statin therapy,” the authors wrote. “Validated clinical decision tools which can predict cholesterol response to statins, or to non-statin drugs, with interventions to help clinicians to tailor and optimise statin treatments for individual patients are needed.”

An editorial noted that simplified recommendations and algorithms may also facilitate guideline implementation.

“Patients and society should be educated on the scientific evidence documenting the benefits of lipid-lowering therapy and anti-statin propaganda based on pseudoscience should be strongly disavowed and demystified by health authorities,” the editorial said. “Reassurance of statin safety should be emphasised to both doctors and patients in order to diminish excessive, unrealistic concerns.”