New Treatment Option For Patients Not Reaching Cholesterol Targets On Statins, UK

Main Category: Statins
Also Included In: Cholesterol
Article Date: 20 Aug 2009 - 1:00 PDT

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Merck Sharp & Dohme Limited (MSD) announced the UK launch of 'Tredaptive'® (nicotinic acid/laropiprant) 1000 mg/20 mg (two tablets once daily maintenance dose), a new treatment option for dyslipidaemia. It is indicated for patients with combined mixed dyslipidaemia or primary hypercholesterolaemia and should be used in combination with a statin when the cholesterol lowering effect of statin monotherapy is inadequate, or as monotherapy when statins are considered inappropriate or not tolerated. Diet and other non-pharmacological treatments, such as exercise and weight loss, should continue during therapy.

Treatment with statins has represented a major advance in lipid management which can provide a relative reduction in cardiovascular disease (CVD) risk of around 30% (versus placebo). However, many patients do not achieve cholesterol targets on statin alone and despite statin treatment there is still a significant CVD residual risk in some patients.

In clinical studies, 2,548 patients have been randomised to treatment with nicotinic acid/laropiprant (1000 mg/ 20 mg or 2000 mg/40 mg) for up to 52 weeks. In an efficacy study, treatment with the drug with or without a statin (n=696) has been shown to lower LDL-C levels by 18% and triglycerides by 26% and to raise HDL-C levels by 20% (placebo adjusted) for a 24 week period.

Dr George Kassianos, GP in Bracknell and Fellow of the European Society of Cardiology stated "With the NICE Lipid Guidelines setting more stringent goals for secondary prevention patients, a statin may not be sufficient for some patients. We regularly combine hypertension therapies to optimise blood pressure management. In order to help manage a patient's overall cardiovascular risk, combination therapy to address not just LDL-C but also HDL-C and triglycerides, is increasingly being recognised as a valuable approach. This may be particularly important for the management of patients at high risk such as secondary prevention patients, those with diabetes, and South Asian populations.

Nicotinic acid has been widely recognised as an effective lipid-modifying therapy for over 50 years, but its use has been limited due to a flushing side-effect. The laropiprant component in 'Tredaptive' is an anti-flushing agent. Compared with extended release nicotinic acid (ERN) starting dose (1g), patients with 'Tredaptive' 1g/20 mg experienced significantly (p<0.001) less flushing categorised as none/mild, moderate, severe and extreme.Beyond week 6, patients in the ERN group (n=529) continued to experience a level of moderate, severe or extreme flushing comparable to that observed at week 6, while in the 'Tredaptive' group (n=781), the flushing signal gradually subsided to a level that approximated placebo (n=262).11 This reduction in flushing has led to patients on 'Tredaptive' being less likely to discontinue treatment due to flushing compared to ER nicotinic acid treated patients (10.2% vs 22.2%, respectively; P < 0.001).

'Tredaptive' contains 1000 mg of nicotinic acid and 20 mg of laropiprant in each tablet. The starting dose is one tablet once a day. After four weeks, it is recommended that patients be advanced to the maintenance dose of 2000 mg/40 mg taken as two tablets once daily.

Professor Ian Young, Professor of Medicine, Queen's University Belfast commented: "'Tredaptive' provides clinicians with a new treatment option that can offer a comprehensive approach to lipid management by helping us address LDL-C levels and beyond11 in order to help reduce cardiovascular disease risk. Studies have shown benefits in managing across three important cardiovascular risk factors - high LDL-C, low HDL-C and elevated triglycerides levels.The significant reduction in flushing and a simple two step titration may help patients reach and continue with the therapeutic maintenance dose of nicotinic acid, helping to give them the treatment's optimum benefit."

In clinical studies, 'Tredaptive' was generally well tolerated. Flushing is the most common side effect and is most prominent in the head, neck and upper torso. Other drug-related adverse reactions (reported by the investigators as possibly, probably, or definitely related) in controlled clinical trials in ≥1% of patients treated with nicotinic acid /laropiprant for up to 1 year include elevations in ALT and/or AST (consecutive ≥ 3X ULN), fasting glucose and uric acid; nervous system disorders (dizziness, headache, paraesthesia); gastrointestinal disorders (diarrhoea, dyspepsia, nausea, vomiting); skin and subcutaneous tissue disorders (erythema (redness of the skin), pruritus (itching), rash, urticaria) and general disorders like feeling hot.

Nicotinic acid treatments have been associated with increases in fasting blood glucose levels. Diabetic or potentially diabetic patients should be observed closely and adjustment of diet and/or hypoglycaemic therapy may be necessary.

Source
Merck Sharp & Dohme Limited