Increasing the use of PCSK9 inhibitors in patients at high-risk of cardiovascular disease (CVD) supports national efforts to address one of UK’s greatest health burdens
The sombre facts and figures regarding cardiovascular disease (CVD) across the UK are hard to ignore:
The impact that CVD, the second-largest cause of death in the UK, has on patients, society and our economy is sobering indeed. Although the widespread use of lipid-lowering therapies (including statins) has helped in the fight to reduce the risks associated with high cholesterol, over 60% of patients in the UK cannot reach target low-density lipoprotein (LDL-C) levels with this treatment. Looking at the continued societal and economic effect that CVD has across the country, the fight against high cholesterol is still an important one. The job is not yet done.
Statins remain the treatment of choice for lowering LDL-C levels for both primary and secondary prevention of CVD events, representing the second largest class of drugs by spend for the NHS. With some statins becoming generic, particularly high potency statins like atorvastatin, this has helped increase their use.
The debate of statins versus PCSK9 inhibitors should focus on the individual patient; the high-risk CVD patient who may be statin intolerant or where statins fail to achieve target LDL-C goals
Statins have decades of clinical data to show that the class can lower LDL-C levels and in turn the risk of CVD, but statins don’t work for everyone.
In particular, patients with an inherited cholesterol condition called familial hypercholesterolaemia (FH), patients who are statin intolerant, and patients diagnosed with clinical atherosclerotic CVD often remain at high-risk following lipid-lowering treatments, such as statins. A refreshed focus on individual patients and tailored treatment is one of the solutions to this problem.
PCSK9 inhibitors are innovative, highly effective treatments to help significantly reduce cholesterol levels for high-risk CVD patients when used in combination with statins. As part of the ODYSSEY LONG TERM trial comparing change in LDL-C with Praluent®▼(alirocumab), biweekly injections of 150 mg of alirocumab resulted in a 61% reduction in LDL-C levels from baseline compared to an increase of 0.8% following placebo after 24 weeks. 79.3% of patients reached the goal of less than 70 mg LDL-C per decilitre, compared with 0.8% in the placebo group. Demonstrable efficacy in reducing LDL-C in high-risk patients, coupled with NICE approval, means that the uptake of PCSK9 inhibitors is likely to increase. The reduction in CV outcomes could result in cost savings of over £850,000 for the NHS within five years.
The debate of statins versus PCSK9 inhibitors should focus on the individual patient; the high-risk CVD patient who may be statin intolerant or where statins fail to achieve target LDL-C goals. The use of PCSK9 inhibitors with this patient population, who is at greatest risk of further CV events, is a cost-effective intervention.
Despite figures included in the NICE impact report regarding the use of PCSK9 inhibitors, the uptake of alirocumab and evolocumab is still below the institution’s original estimate of 4,500 people in England during 2017/18, and varies widely across England and Wales. By recognising the value of PCSK9 inhibitors, we can help patients across the UK achieve their target LDL-C levels and in turn reduce their risk of heart attacks and stroke.
Please refer to the Praluent Summary of Product Characteristics for full prescribing details.
Presentation: Single-use pre-filled pen containing 75 mg or 150 mg Alirocumab in 1 ml solution. Alirocumab is a human IgG1 monoclonal antibody produced in Chinese Hamster Ovary cells by recombinant DNA technology. Indications: Praluent is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet: in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated. Dosage and Administration: The usual starting dose for Praluent is 75 mg administered subcutaneously once every 2 weeks. Patients requiring larger LDL-C reduction (>60%) may be started on 150 mg once every 2 weeks or 300 mg once every 4 weeks (monthly), administered subcutaneously. If a dose is missed, the patient should administer the injection as soon as possible and thereafter resume treatment on the original schedule. Lipid levels can be assessed 4 to 8 weeks after treatment initiation or titration, and dose adjusted accordingly (up-titration or down-titration). If additional LDL-C reduction is needed in patients treated with 75 mg once every 2 weeks or 300 mg once every 4 weeks (monthly), the dosage may be adjusted to the maximum dosage of 150 mg once every 2 weeks. Praluent is injected as a subcutaneous injection into the thigh, abdomen or upper arm. A dose of 300 mg should be given as two 150 mg injections consecutively at two different injection sites. Praluent should not be injected into areas of active skin disease or injury such as sunburns, skin rashes, inflammation, or skin infections. Praluent must not be co-administered with other injectable medicinal products at the same injection site. The patient may either self-inject Praluent, or a caregiver may administer Praluent, after guidance has been provided by a healthcare professional on proper subcutaneous injection technique. Praluent pre-filled pens should be allowed to warm to room temperature for 30 to 40 minutes prior to use. Elderly: No dose adjustment needed Children: The safety and efficacy of Praluent in children and adolescents less than 18 years of age have not been established. No data are available. Hepatic impairment: No dose adjustment is needed for patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment (Child-Pugh C) have not been studied. Praluent should be used with caution in patients with severe hepatic impairment. Renal impairment: No dose adjustment is needed for patients with mild or moderate renal impairment. In clinical studies, there was limited representation of patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2). Praluent should be used with caution in patients with severe renal impairment. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions and Warnings: General allergic reactions, including pruritus, as well as rare and sometimes serious allergic reactions such as hypersensitivity, nummular eczema, urticaria, and hypersensitivity vasculitis have been reported in clinical studies. If signs or symptoms of serious allergic reactions occur, treatment with Praluent must be discontinued and appropriate symptomatic treatment initiated. Interactions: Since alirocumab is a biological medicinal product, no pharmacokinetic effects of alirocumab on other medicinal products and no effect on cytochrome P450 enzymes are anticipated. Statins and other lipid lowering therapies can increase clearance of alirocumab, however LDL-C reduction was maintained on two weekly alirocumab administration. Pregnancy and Lactation: There are no data from the use of Praluent in pregnant women. Alirocumab is an IgG1 antibody and is expected to cross the placental barrier. The use of Praluent is not recommended during pregnancy unless the clinical condition of the patient warrants it. Praluent is not recommended in breast-feeding women when colostrum is produced; for the rest of the breast-feeding period, a decision should be made whether to discontinue nursing or to discontinue Praluent. Fertility: In animal studies, there were no adverse effects on surrogate markers of fertility. There are no data on adverse effects on fertility in humans.
For full information on Adverse events please consult the Praluent Summary of Product Characteristics.
Adverse Reactions: In pooled controlled studies. Common reactions (≥1/100 to <1/10) are local injection site reactions (including erythema/redness, itching, swelling, pain/tenderness), upper respiratory tract signs and symptoms (including mainly oropharyngeal pain, rhinorrhoea, sneezing), and pruritus. The most common adverse reactions leading to treatment discontinuation in patients treated with Praluent were local injection site reactions. Most injection site reactions were transient and of mild intensity. General allergic reactions were reported more frequently in the Praluent group than in the control group, mainly due to a difference in the incidence of pruritus. The observed cases of pruritus were typically mild and transient. Rare (≥1/10,000 to <1/1,000) and sometimes serious allergic reactions such as hypersensitivity, hypersensitivity vasculitis, urticaria, and eczema nummular have been reported in controlled clinical studies. No difference in the safety profile was observed between the 75 mg and 150 mg doses used in the phase III program. The safety profile observed in patient treated with 300 mg every 4 weeks was similar to that described for the clinical study program using a 2-week dosing regimen, but with a higher rate of local injection site reactions.
Special precautions for storage: Store in a refrigerator (2°C to 8°C). Do not freeze. Praluent can be stored outside the refrigerator (below 25 °C) protected from light for a single period not exceeding 30 days. After removal from the refrigerator, the medicinal product must be used within 30 days or discarded. Keep the pen in the outer carton in order to protect from light.
Package Quantities and Basic NHS Price: Pack of 1 pre-filled pen of 75 or 150 mg/ml: £168. Pack of 2 pre-filled pens of 75 or 150 mg/ml: £336. Legal Category: POM. Marketing Authorisation Numbers: 1x 75 mg: EU/1/15/1031/001, 2x 75 mg: EU/1/15/1031/002, 1x 150 mg: EU/1/15/1031/007, 2x 150 mg: EU/1/15/1031/008. Marketing Authorisation Holder: sanofi-aventis groupe, 54 rue La Boétie, F - 75008 Paris, France. Further information is available from: Medical Information Department, Sanofi, One Onslow Street, Guildford, GU1 4YS, Tel; 0845 372 7101 Date of Revision:November 2016
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard
Adverse events should also be reported to the Sanofi drug safety department on 01483 55 4242