PEARL: A Non-interventional Study of Real-World Alirocumab Use in German Clinical Practice

Parhofer, Klaus G.; Stritzky, Berndt von; Pietschmann, Nicole; Dorn, Cornelia; Paar, W. Dieter

doi:10.1007/s40801-019-0158-0

Cited by 17 publications

(15 citation statements)

References 29 publications

(37 reference statements)

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“…This relatively high number of statin-intolerant patients is due to enrolled patients were being treated at a lipid clinic that specializes in the treatment of statin-intolerant patients. A similar ratio of statin-intolerant patients was observed in the German PEARL real-world study [ 38 ]. Patients without statin therapy demonstrated significantly lower reductions in LDL-C from baseline to week 4 than did patients on background statins (53.1% and 60.2%, respectively; P < 0.0001).…”

Section: Discussionsupporting

confidence: 81%

PCSK9 Inhibitors in a German Single-Center Clinical Practice: Real-World Treatment of Patients at High Cardiovascular Risk Over 68 Weeks

Hollstein

Kassner

Grenkowitz

et al. 2020

Am J Cardiovasc Drugs

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Aims Several the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients at high/very high cardiovascular risk who are inadequately treated with maximally tolerated lipid-lowering therapies (LLTs). Objectives We assessed the effectiveness and safety of the PCSK9i alirocumab and evolocumab in a single-center clinical practice for up to 68 weeks. Methods In this prospective, open-label study conducted in Germany, 635 enrolled patients were treated with alirocumab [75 or 150 mg every 2 weeks (Q2W)] or evolocumab (140 mg Q2W) according to European Society of Cardiology/European Atherosclerosis Society guidelines (low-density lipoprotein cholesterol [LDL-C] > 1.81/2.59 mmol/L (70/100 mg/dL), depending on cardiovascular risk]. Investigators were able to adjust LLTs, including PCSK9i, according to their own clinical judgment. The primary effectiveness endpoint was LDL-C reduction from baseline to week 68. Results At baseline, approximately 50% of patients were statin intolerant, and approximately 90% reported a history of cardiovascular disease. LDL-C reductions remained generally unchanged from weeks 4 to 68 in each treatment group. At week 68, LDL-C mean percentage changes from baseline were − 41.7% (alirocumab 75 mg Q2W), − 53.7% (alirocumab 150 mg Q2W), and − 54.1% (evolocumab 140 mg Q2W). LDL-C reduction was 7.1% greater in patients receiving statins than in those not receiving statins because of statin intolerance ( P < 0.0001). PCSK9i consistently improved levels of other lipoproteins throughout. Overall, 47.1% of patients reported adverse events at week 68. Conclusions Consistent with clinical trial findings, alirocumab and evolocumab improved lipid levels in a real-world setting in patients with high baseline LDL-C levels despite receiving maximally tolerated LLTs. PCSK9i were generally well-tolerated. Electronic supplementary material The online version of this article (10.1007/s40256-020-00411-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 81%

PCSK9 Inhibitors in a German Single-Center Clinical Practice: Real-World Treatment of Patients at High Cardiovascular Risk Over 68 Weeks

Hollstein

Kassner

Grenkowitz

et al. 2020

Am J Cardiovasc Drugs

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“…A recent study on effectiveness and safety in a real-life setting in Germany largely confirmed findings from the ODYSSEY study program 11 . As real-world data are still sparse, the current observational study was conducted to estimate the effectiveness and safety of alirocumab in an Austrian population.…”

Section: Introductionsupporting

confidence: 54%

“…Based on the inclusion criteria that stipulated patients to be on treatment with alirocumab, it could be expected that the majority of patients had a total or partial statin intolerance. The design of this study was concordant with a prior noninterventional study (PEARL) conducted in Germany in 619 patients 11 . A crucial difference to the real-world data in Germany is that patients were recruited from different specialists: in Austria, prescribing physicians were endocrinologists and were based in a hospital setting (according to the Austrian reimbursement regulation).…”

Section: Discussionmentioning

confidence: 87%

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Efficacy and tolerability of alirocumab in Austrian clinical practice – results of the non-interventional PEARL-AT study

Leitner

Toplak

Kedenko

et al. 2020

Current Medical Research and Opinion

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Objective: Proprotein convertase subtilisin/kexin type 9 inhibition can be an effective treatment in patients with primary hypercholesterolemia, particularly in cases with concomitant coronary heart disease, peripheral artery occlusive disease or cerebrovascular occlusive disease for secondary prevention after an acute atherosclerotic ischemic event. The primary objective of the PEARL-AT study was to assess effectiveness and safety of alirocumab in a real-world setting in Austria. Methods: Non-interventional, prospective study conducted across Austria between September 2016 and July 2018. 113 patients, for whom the decision for treatment with alirocumab according to the Austrian Summary of Product Characteristics (SmPC) was made, were enrolled and were followed-up over 24 weeks. The primary endpoint of the study was the average change of low density lipoprotein cholesterol (LDL-C) levels by week 24. Results: In total, 112 patients with at least one post-baseline visit were included. Alirocumab was initiated using 75 mg (57.1%) and 150 mg (42.9%) every two weeks. Average LDL-C levels decreased by 75.0 mg/dl at week 24 in 87 patients with available LDL-C at baseline and week 24 (in 25 patients LDL-C was missing at least at one time point). The mean relative change of LDL-C was À50.0% (median: 57.8%, SD: 28.4). Throughout the study, 46 adverse events were documented in 21 (18.6%) patients. The most frequent adverse events were gastrointestinal disorders. Conclusions: The present data indicate a good overall efficacy of alirocumab in a real-world Austrian population. Effectiveness and safety were both in line with the clinical trial program as well as previous real-world observations.

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“…Therapeutic approaches to lower LDL-C other than statins therefore play an important role in clinical practice. Real-world data from Germany underline the importance of antibodies against PCSK9 in this setting by showing that among patients treated with alirocumab, 73% had partial or total statin intolerance ( Parhofer et al, 2019 ).…”

Section: Ldl-c Lowering With Pcsk9 Antibodiesmentioning

confidence: 99%

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

2020

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In 2003, clinical observations led to the discovery of the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism. Functional studies demonstrated that PCSK9 binds to the low-density lipoprotein (LDL) receptor directing it to its lysosomal degradation. Therefore, carriers of gain-of-function mutations in PCSK9 exhibit decreased expression of LDL receptors on the hepatocyte surface and have higher LDL cholesterol (LDL-C) levels. On the contrary, loss-of-function mutations in PCSK9 are associated with low LDL-C concentrations and significantly reduced lifetime risk of cardiovascular disease. These insights motivated the search for strategies to pharmacologically inhibit PCSK9. In an exemplary rapid development, fully human monoclonal antibodies against PCSK9 were developed and found to effectively reduce LDL-C. Administered subcutaneously every 2–4 weeks, the PCSK9 antibodies evolocumab and alirocumab reduce LDL-C by up to 60% in a broad range of populations either as monotherapy or in addition to statins. Two large cardiovascular outcome trials involving a total of ∼46,000 cardiovascular high-risk patients on guideline-recommended lipid-lowering therapy showed that treatment with evolocumab and alirocumab led to a relative reduction of cardiovascular risk by 15% after 2.2 and 2.8 years of treatment, respectively. These findings expanded the armamentarium of pharmacological approaches to address residual cardiovascular risk associated with LDL-C. Furthermore, the unprecedented low LDL-C concentrations achieved (e.g., 30 mg/dL in the FOURIER study) suggest that the relationship between LDL-C and cardiovascular risk is without a lower threshold, and without associated adverse events during the timeframe of the studies. The side effect profile of PCSK9 antibodies is favorable with few patients exhibiting injection-site reactions. Currently, the access to PCSK9 antibodies is limited by high treatment costs. The development of novel approaches to inhibit PCSK9 such as the use of small interfering RNA to inhibit PCSK9 synthesis seems promising and may soon become available.

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PEARL: A Non-interventional Study of Real-World Alirocumab Use in German Clinical Practice

Cited by 17 publications

References 29 publications

PCSK9 Inhibitors in a German Single-Center Clinical Practice: Real-World Treatment of Patients at High Cardiovascular Risk Over 68 Weeks

PCSK9 Inhibitors in a German Single-Center Clinical Practice: Real-World Treatment of Patients at High Cardiovascular Risk Over 68 Weeks

Efficacy and tolerability of alirocumab in Austrian clinical practice – results of the non-interventional PEARL-AT study

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

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