Poor response to statins may signal progression in blocked arteries

Lowered response to statin therapy may indicate more rapidly progressive atherosclerosis, according to a meta-analysis. These patients, representing one-fifth of the study population, were more likely to have significant arterial blockage progression at follow up than those who responded to treatment.

The study was published Feb. 26 in Arteriosclerosis, Thrombosis and Vascular Biology

Yu Kataoka, MD, of the South Australian Health and Medical Research institute at the University of Adelaide, and colleagues analyzed the results of seven clinical studies. These studies, together, encompassed 647 patients with coronary artery disease with both recorded cholesterol levels and ultrasound imaging results.

Twenty percent of patients were what Kataoka et al called hyporesponders. These individuals, despite statin therapy, saw little response to low-density lipoprotein (LDL) cholesterol levels. Hyporesponders were younger, male and obese compared to the rest of the study population. They were less likely to be treated with beta-blockers, but were more likely to be treated with atorvastatin (Lipitor, Pfizer) and simvastatin (Zocor, Merck) as opposed to rosuvastatin (Crestor, AstraZeneca). While with some statins, dosing was similar between those who responded and those who didn’t, those who didn’t were more likely to receive lower doses of atorvastatin and rosuvastatin.

These patients had similar baseline atheroma burden and they had smaller elastic membrane and lumen volume measurements. However, greater atheroma progression was noted among hyporesponders than those who responded well to statin therapy at follow-up. Percent atheroma volume progressed 1.19 percent in hyporesponders as opposed to 0.09 percent in the rest of the study group.

Patients who did not respond well to statins were less likely to have regression of percent atheroma volume. They also had greater reduction in lumen volume at follow-up (-16.53 vs -7.81 mm3). Likewise, these patients exhibited small increase in LDL cholesterol levels, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol, in spite of statin use.

While Kataoka et al speculated on a number of reasons for these findings, they noted that drug compliance was not one of them; observed compliance rates were greater than 90 percent in all seven studies.

“Our current study underscores monitoring LDL-C level after commencement of statin(s) to ensure adequate response to statin therapy. The current analysis also highlights the clinical needs for emerging antiatherosclerotic therapies, which modify additional targets in statin hyporesponders,” Kataoka et al wrote.