Highlights
- •Therapeutic adhesion with PCSK9i is greater than with other hypolipidemics.
- •The effectiveness of PCSK9i is similar to that referred to in clinical trials.
- •Therapeutic adherence and effectiveness are maintained in the long-term.
- •This is the first published study on the therapeutic adherence of PCSK9i.
- •Adverse reactions with PCSK9i are sparse and mild.
Abstract
Purpose
To evaluate the effectiveness, adverse reactions, and adherence to treatment of hypolipidemic
inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9is) in a context
of real clinical practice.
Methods
We present an observational, retrospective, descriptive, multicenter study of patients
with hypercholesterolemia who began treatment with PCSK9is between January 2017 and
December 2019, with a minimum treatment period of 3 months. The main variable we recorded
was the frequency of cardiovascular events (cardiovascular death, myocardial infarction,
stroke, coronary revascularization, and hospitalization for unstable angina) in patients
treated with PCSK9is. We recorded patient demographic characteristics and cardiovascular
risk factors at onset of treatment as well as LDL-C levels and their reductions at
3, 6, 12, and 24 months. We calculated adherence to treatment and recorded the adverse
reactions during treatment.
Findings
A total of 154 patients were studied, 64 (41.6%) of whom were treated with alirocumab
and 90 (58.4%) with evolocumab. The initial dose of alirocumab was 75 mg every 14
days in 48 patients (75%) and 150 mg eery 14 days in 16 (25%). All patients who in
the evolocumab group received a dose of 140 mg every 14 days. The mean (SD) basal
LDL-C level was 159.6 (50.1) mg/dL, the level at 3 months was 87.9 (49.9) mg/dL (mean
[SD] decrease, 44.5% [28.2%]), the level at 6 months was 86.7 (49.2) mg/dL (mean [SD]
decrease, 46.3% [25.6%]), and the level at 12 months was 80.5 (41.4) (mean [SD] decrease,
48.9% [23.0%]). These values were maintained at 24 months (mean [SD], 80.3 [41.8]
mg/dL; mean [SD] decrease, 47.9% [27.8%]). The percentage decrease of LDL-C for both
drugs was approximately 50%, which was maintained until 24 months after treatment.
Six patients (3.9%) presented with some cardiovascular event: acute myocardial infarction
(2 [1.3%]), stroke (1 [0.65%]), coronary revascularization (1 [0.65%]), and hospitalization
for unstable angina (2 [1.3%]). We did not see any adverse reactions related to PCSK9i
treatment in 76.5% of patients. In the first 6 months, adherence to treatment with
PCSK9is, measured as the possession ratio, was a mean (SD) of 99.4% (3.9%). In the
rest of the study period (6–24 months), the mean (SD) adherence to treatment was 99.2%
(4.7%).
Implications
The frequency of cardiovascular events in patients treated with PCSK9is was low and
occurred despite adequate adherence to treatment (100% possession ratio) with PCSK9is
and concomitant treatment with other hypolipidemics. The effectiveness of PCSK9is
is similar to that referred to in other published studies with PCSK9is, and this was
maintained in the long term (24 months) with few adverse events, all of which were
mild.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epidemiología y prevención de las enfermedades cardiovasculares.in: Piédrola Gil. Medicina Preventiva y Salud Pública. Elsevier España, S.L.2008
- 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.Eur Heart J. 2020; Jan 1; 41: 111-188
- Guideline on clinical investigation of medicinal products in the treatment of lipid disorders.(EMA/CHMP/748108/2013. Available at:)https://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/01/WC500159540.pdfDate accessed: August 13, 2020
- Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data.Expert Opin Drug Saf. 2019; Jul; 18: 611-621
- European Public Assessment Report. Praluent Recommended for Approval to Lower Cholesterol.EMA/CHMP/490200/2015, 24 July 2015 (Available at:)
- Repatha to offer therapy for patients unable to control high cholesterol with currently available treatment.(Available at:)
- Data sheet praluent.(Available at:)https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125559Date accessed: August 26, 2020
- Data sheet Repatha.(Available at:)https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125522Date accessed: August 26, 2020
- FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease.N Engl J Med. 2017; May 4; 376: 1713-1722
- ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome.N Engl J Med. 2018; Nov 29; : 2097-2107
- PCSK9 inhibitors in clinical practice: delivering on the promise?.Atherosclerosis. 2018; Mar; 270: 205-210
- PCSK9 inhibitors in clinical practice: novel directions and new experiences.Hellenic J Cardiol. 2019; Nov 26; S1109–9666: 30276-30283
- Lipid-lowering therapy with PCSK9-inhibitors in the real-world setting: two-year experience of a regional lipid clinic.Cardiovasc Ther. 2018; Oct; 36: e12439
- ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II Study.J Am Heart Assoc. 2016; Sep 13; 5e003421
- ODYSSEY COMBO II Investigators. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.Eur Heart J. 2015; May 14; 36: 1186-1194
- Long-term efficacy and safety of evolocumab in patients with hypercholesterolemia.J Am Coll Cardiol. 2019; Oct 29; 74: 2132-2146
- Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study.Lipids Health Dis. 2017; Jan 23; 16: 19
- PCSK9 inhibitors: mechanism of action, efficacy, and safety.Rev Cardiovasc Med. 2018; 19: S31-S46
- ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; Apr 16; 372: 1489-1499
- Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial.JAMA. 2012; Dec 19; 308: 2497-2506
- Efficacy and safety of PCSK9 monoclonal antibodies.Expert Opin Drug Saf. 2019; Dec 18; : 1191-1201
- Real-world use of PCSK9 inhibitors: a single-center experience.J Int Med Res. 2019; Jan; 47: 265-270
- Lipid-lowering therapy with PCSK9-inhibitors in the management of cardiovascular high-risk patients: effectiveness, therapy adherence and safety in a real-world cohort.Cardiol J. 2018; 25: 32-41
- Real world treatment patterns of PCSK9 inhibitors among patients with dyslipidemia in Germany, Spain, and United Kingdom.Curr Med Res Opin. 2019; May; 35: 829-835
- Association of a combined measure of adherence and treatment intensity with cardiovascular outcomes in patients with atherosclerosis or other cardiovascular risk factors treated with statins and/or ezetimibe.JAMA Netw Open. 2018; Dec 7; 1e185554
- Assessing the adherence to and the therapeutic effectiveness of hypolipidemic agents in a population of patients in Brazil: a retrospective cohort study.Pharm Pract (Granada). 2014; Apr; 12: 378
Article info
Publication history
Published online: March 09, 2021
Accepted:
February 15,
2021
Identification
Copyright
© 2021 Elsevier Inc.
