Treament intertia for lipid-lowering therapy in patients with FH and CVD

Treatment Inertia in Patients with Familial Hypercholesterolemia

Literature - Langer A, Mancini J, Tan M, et al. - J Am Heart Assoc. 2021;190:e020126. DOI: 10.1161/JAHA.120.020126

Introduction and methods

The Canadian Cardiovascular Society (CCS) guidelines recommend LDL-c lowering therapy (LLT) with high efficacy statin therapy and addition of ezetimibe and/or PCSK9i as needed in patients with established CVD, if LDL-c levels are not decreased by at least 50% or below 2.0 mmol/L [1]. The CCS recommends the same therapeutic approach in patients with FH, albeit with an LDL-c attainment goal of <2.5 mmol/L [2]. Despite these treatment guidelines, many patients with elevated LDL-c do not achieve LDL-c target goals [3-6]. A recent study, however, has demonstrated that physician support based on a reminder system for recommended LLT led to an increase in the proportion of patients who achieved guideline-recommended LDL-c levels [7]. This post hoc analysis specifically assessed the care gap in patients with FH with respect to LLT. Furthermore, this analysis explored whether lipid management differed between patients with CVD and patients with FH.

The Guidelines Oriented Approach to Lipid Lowering (GOAL) Canada was an investigator-initiated interventional program. The intervention was physician education based on lipid management reminders when entering LLT data in the electronic case report form. A total of 177 physicians (58% primary care and 42% specialists) enrolled 2009 patients (at least 12 patients per physician) with clinical vascular diseases such as, CAD, PAD, cerebrovascular disease, abdominal aortic aneurysm, or with FH. In addition, eligible patients had to have LDL-c levels of >2 mmol/L at baseline while receiving maximally tolerated statins (having tried a minimum of 2 statins, each at least on 2 reduced doses) for at least 3 months before enrollment. A total of 1054 (52.4%) patients with CVD, 636 (31.7%) patients with FH, and 319 (15.9%) patients with FH and established CVD were included. LLT was assessed on enrollment (visit 1) and twice during follow-up (visit 2 and 3, each between ~4 to 6 months apart). The prespecified primary endpoint was the proportion of patients who achieved the CCS recommended LDL-c targets of ≥50% reduction or<2 mmol/L in patients with CVD and ≥50% reduction or <2.5 mmol/L in patients with FH.

Main results

  • At baseline, 70.6% of patients with FH received statin therapy compared to 79.2% of patients with CVD (P=0.0001). A larger proportion of patients with FH were treated with ezetimibe compared to those with CVD (28.1% vs. 20.4%, P=0.0003). 46.6% Of patients with FH used high-intensity statins compared to 58.1% of patients with CVD or 67.7% of patients with FH and CVD (both P=0.0001).
  • 45.3% of patients with FH were already at LDL-c target goal at baseline. At visit 3, 73.6% of patients with FH were at target.
  • 22.0% of patients with FH who had not achieved their LDL-c goals at baseline, attained their goal at the last available follow-up visit, compared to 45.8% of patients with CVD (P<0.0001) and 55.2% of patients with FH + CVD (P<0.0001).
  • Significant LDL-c reductions from baseline to visit 3, were observed in patients with FH (-1.4±1.6 mmol/L, P=0.0001), with CVD (-0.8±1.2 mmol/L, P<0.0001), and in those with FH and CVD (-1.4±1.4 mmol/L, P=0.0001). A larger LDL-c reduction was seen in patients with FH who were not on their LDL-c attainment goal at baseline compared to those who were (-1.6±1.6 mmol/L vs. -1.2±1.8 mmol/L, P=0.02).
  • The strongest predictors of LDL-c goal attainment were PCSK9i treatment (OR 11.4, 95% CI: 8.7-15.0, P<0.0001), statin use (OR 5.3, 95% CI: 4.2-6.7, P<0.0001), ezetimibe therapy (OR 1.6, 95% CI: 1.3-1.9, P<0.0001), and FH diagnosis (OR 2.7, 95% CI:2.0-3.5, P=0.0001).


This post hoc analysis suggests that physician reminders for recommended LLT led to an increase in the proportion of patients with FH and/or CVD achieving LDL-c treatment goals. However, treatment inertia remains to exists in patients with FH, including those with established CVD.


1. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263–1282.

2. Brunham LR, Ruel I, Aljenedil S, et al. Canadian cardiovascular society position statement on familial hypercholesterolemia: update 2018. Can J Cardiol. 2018;34:1553–1563

3. Hackam DG, Leiter LA, Yan AT, et al. Missed opportunities for secondary prevention of cardiovascular disease in Canada. Can J Cardiol. 2007;23:1124–1130.

4. Yan AT, Yan RT, Tan M, et al. Contemporary management of dyslipidemia in high-risk patients: targets still not met. Am J Med. 2006;119:676–683.

5. Petrella RJ and Merikle E, Jones J. Prevalence and treatment of dyslipidemia in Canadian primary care: a retrospective cohort analysis. Clin Ther. 2007;29:742–750.

6. Rapezzi C, Biagini E, Bellis P, Cafiero M, Velussi M, Ceriello A, Cooke RMT, Schweiger C, Investigators EASY. Exploring the gap between National Cholesterol Education Program guidelines and clinical practice in secondary care: results of a cross-sectional study involving over 10 000 patients followed in different specialty settings across Italy. J Cardiovasc Med. 2008;9:878–887.

7. Langer A, Tan M, Goodman SG, et al. GOAL Canada: physician education and support can improve patient management. CJC Open. 2020;2:49– 54. DOI: 10.1016/j.cjco.2019.12.002

Find this article online at J Am Heart Assoc.

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