Introduction PCSK9 Inhibitors (PCSK9 I) are a new group of drugs for treatment of hyperlipidaemia. These drugs have been available in Denmark since October 2015. From the two existing major outcome studies (FOURIER and ODYSSEY OUTCOMES) it has been shown that there was no significant difference in the risk of serious adverse events, discontinuation due to adverse events, neurocognitive events, diabetes-related events, muscle-related events, or myalgia in the treatment group, compared with the control group. In FOUIRER 12.5% came of treatment; In ODYSSEY the rate was 10.2–14.8%. Although this highlights the efficacy and safety in patients with cardiovascular disease, we have little knowledge of the use, efficacy and safety with these drugs in real-life populations Purpose We aim to describe the demography, the treatment efficacy and the extent of adverse effects among patients treated in Danish lipid clinics. Methods Data on all patients treated with PCSK9 I between October 1st, 2015 and May 1st, 2018 were obtained from lipid clinics in Denmark. A database containing information on medications before treatment, adverse effects, plasma lipids (LDL-C, Triglyceride, High density lipoprotein cholesterol (HDL-C)) and supplementary blood tests was created. Levels of plasma lipids and organ markers (Creatinine, Hba1c or Alanine aminotransferase (ALAT)) at baseline and at follow up visits were analysed. Results Nationwide, 383 patients were included, an estimated 90% of all patients undergoing treatment with PCSK9 I in Denmark. A large proportion (n=243 - 63.4%) were described as statin intolerant and only 94 patients were receiving statins at baseline. Adverse effects (AE) were reported by 71 patients (18.5%) on PCSK9 I therapy and 50 patients (13.1%) stopped treatment. Most common AE were flu like symptoms and musculoskeletal aches. In two cases an increase in serum creatinine kinase was detected. One case of angioedema and three cases of local reactions to injections had been documented. No case of anaphylaxis was reported. Of the 71 patients with AEs 55 (77.5%) were statin intolerant. Of the 50, who came off treatment, 43 (86.0%) were statin intolerant. When treatment was stopped 15 patients (30.0%) tried the alternative PCSK9 Inhibitor (cross over). Of those, nine patients were able to tolerate the alternative PCSK9 I treatment. Conclusion Many patients (18.3%) reported AEs on a wide range of symptoms, but the rate of patients terminating PCSK9 I treatment was the same as found in the outcome studies (13.1% vs. 12.2 and 10.2–14.8%). Most of the patients who stopped treatment were statin intolerant and produced the same symptoms, as they had experienced with statins. Interestingly, nine of the 15 patients that were switched to the alternate PCSK9 I seems to tolerate this treatment.
Introduction Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 I) are a new group of drugs for treatment of hypercholesterolaemia. At present there are two available drugs evolocumab and alirocumab, which lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting the enzyme proprotein convertase subtilisin/kexin type 9. Both evolocumab and alirocumab outcome data (FOURIER and ODYSSEY OUTCOMES respectively) have shown a reduced risk of myocardial infarction, stroke, and coronary revascularization without adverse effects. Patients included in these trials had existing atherosclerotic cardiovascular disease and all patients received maximum-tolerated statin. In the FOURIER trail 100% of the patients received statin and 69% high intensity statin, in the ODYSSEY trial is was 98% and 89%, respectively Purpose In collaboration with lipid clinics in Denmark we aimed to describe the clinical characteristics of patients treated, along with the efficacy of LDL-C reduction of such treatment in a real-life population. Methods We contacted lipid and cardiological clinics throughout Denmark and obtained clinical data on the majority of patients treated with PCSK9 I in Denmark between October 1st, 2015 and May 1st, 2018. A database containing information on medical history, medications used prior to PCSK9 I initiation, adverse events and plasma lipids including LDL-C was created. Records of baseline LDL-C and at follow up visits were analysed. Results From October 1st 2015 to may 1st2018, 383 patients were enrolled; an estimated 90% of all patients in Denmark. The distribution of clinical indications for PCSK9 I initiation is shown in figure 1. A total 243 of these patients (63.4%) were characterised as statin intolerant and 225 (58.7%) had familial hypercholesterolaemia. More than two thirds (69.5%) of the patients were given PCSK9 Inhibitors as secondary prophylaxis. Overall LDL was significantly reduced from 5.11 mmol/L (CI [4.95; 5.28]) to 2.46 mmol/L (CI [2.33–2.68]) after the first month of treatment, corresponding to a 48.9% decrease in LDL-C, which persisted without significant changes throughout the two years of observation. Even with this reduction, only about half of the population of both primary and secondary prevention reached their treatment target. This remained unchanged in patients with familial hypercholesterolaemia an those with statin intolerance (Table 1). A subgroup analysis showed a significantly lower LDL in the first 12 months when PCSK9 I were combined with statins versus PCSK9 I as monotherapy (p<0.05) (results not shown). Conclusion Patients treated with PCSK9 I in this real-life do not resemble the populations in the major endpoint studies, as the majority in this real-life population are statin intolerant. Nevertheless, we see an overall reduction of LDL of approx. 50%, even though the number of patients reaching their treatment target remains low (approx. 50% at best).
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