Adherence to statin therapy after inclisiran start, insights from the the DAMAGE registry

Abstract Background Hypercholesterolemia is among the main risk factors for cardiovascular disease, with an estimated prevalence of 39% in the general population. Approximately 50% of the European population aged between 35 and 64 has total cholesterol levels exceeding 250 mg/dL, and over 50 million patients in developed countries are undergoing treatment with lipid-lowering drugs. Inclisiran, the first siRNA available for hypercholesterolemia, can reduce LDL cholesterol levels by 50% when on-top of standard therapy, but some concerns exist on the adherence to oral therapy in patients starting this new drug. This multicenter, retrospective study aims to evaluate the reduction of LDL-c after inclisiran according to the concomitant changes in background therapy (BT) and statin adherence. Methods All consecutive patients starting inclisiran therapy according to national and European guidelines were enrolled from six different refferal centres. The primary endpoint was the difference in LDL-reduction after inclisiran therapy according to changes in BT and statin adherence. Adherence was assessed by the Morisky Green Levine Medication Adherence Scale (MMAS-8) scale and patients divided into high, moderate, and low adherence. The population was also divided according to the changes in BT into patients who discontinued or riduced BT (BT-), patients who continued with the same treatment after inclisiran (BT=) and patients who increased BT after inclisiran start (BT+). Results 132 patients starting inclisiran therapy were consecutively enrolled (67% males, mean age 64 +/- 10 years) and divided according to their MMAS-8 (16% low adherence, 31% moderate, 54% high). Median follow-up was 9 months. 76% of the population were on secondary prevention (67% previous myocardial infarction, 9% previous stroke/TIA). 26% of all patients were defined as "statin-intolerant" according to EAS guidelines. LDL-c reduction achieved after inclisiran was -64% on average but differed widely according to MMAS-8 subgroup (low: -44%, moderate: -62%, high: -77%; p0.01). Figure 1 depicts the average (in mg/dl) LDL-c reduction according to MMAS-8 subgroup. Patients who discontinued or riduced BT after starting inclisiran had a significantly lower benefit in terms of LDL-c reduction (BT-: -19%; BT=-67%; BT+:-81%; p0001, Figure 2). Conclusion Stating adherence and reduction of background therapy can impact on the perceived efficacy of inclirisan in reducing LDL-c in the real life. While its efficacy in highly-adherent patients is very close to the one derived from the phase-III clinical trials, efforts should be made in order to mantain background therapy and promote aherence after SiRNA start.Changes in average LDL-c (mg/dl) Changes in LDL-c (%) according to BT