News in brief from the world of cardiology
Nicotinic acid/laropiprant combination launched in UK
A combination of nicotinic acid and laropiprant (Tredaptive®), for the treatment of dyslipidaemia (particularly combined mixed dyslipidaemia and primary hypercholesterolaemia) has been launched in the UK by Merck Sharp & Dohme.
It should be used in combination with statins when the cholesterol-lowering effect of statin monotherapy is inadequate, and as monotherapy only if statins are thought inappropriate or if they are not tolerated. Diet and other non-pharmacological measures to control lipid levels should be continued.
It is hoped that the addition of the anti-flushing agent laropiprant will lead to wider use of nicotinic acid as a lipid-modifying therapy. Use of the lattter has been limited due to its flushing side-effects, which can be troublesome and lead to the discontinuation of treatment.
In one clinical trial of nearly 800 patients, significantly fewer patients had moderate or greater flushing with the nicotinic acid/laropiprant combination (31%) than with extended-release nicotinic acid (ERN) alone (56%) and significantly fewer patients discontinued treatment with the combination product than with ERN (10% versus 22%, respectively, p<0.001).
This flushing is mediated primarily by release of prostaglandin D2 (PGD2) in the skin, acting through the DP1 receptor. The agent laropiprant is a potent and selective antagonist of DP1. It suppresses the flushing associated with administration of nicotinic acid without affecting lipid levels or interfering with the effects of nicotinic acid on lipids.
In clinical studies, 2,548 patients have been randomised to treatment with nicotinic acid/laropiprant (1,000 mg/ 20 mg or 2,000 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 low-density lipoprotein cholesterol (LDL-C) levels by 18% and triglycerides by 26%, and to raise high-density lipoprotein cholesterol (HDL-C) levels by 20% (placebo adjusted) for a 24-week period.
The product contains 1,000 mg of nicotinic acid and 20 mg of laropiprant per modified-release tablet. The starting dose is one tablet daily; after four weeks, patients should be advanced to the maintenance dose of two tablets once daily.
US approval for dronedarone for AF patients
The US Food and Drug Administration (FDA) has approved dronedarone (Multaq®) 400 mg for patients with atrial fibrillation (AF) or atrial flutter (AFL) as a new treatment option to help improve current management of their disease. Dronedarone is the first drug to be approved in the US that has shown a clinical benefit to reduce cardiovascular hospitalisation in patients with AF/AFL.
The anti-arrhythmic agent is indicated to reduce the risk of cardiovascular hospitalisation in patients with paroxysmal or persistent AF or AFL, with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted. Associated cardiovascular risk factors include age over 70 years, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction <40%.
The FDA approval is based on five international, multi-centre, randomised clinical trials involving nearly 6,300 patients, including the ATHENA study, which showed that dronedarone 400 mg twice daily, in addition to standard therapy, reduced the combined end point of cardiovascular hospitalisation or death from any cause by 24% (p<0.001) when compared to placebo, meeting the study’s primary end point.
Clarification: NICE guidance on type 2 diabetes
The news item entitled ‘New NICE guidelines on new treatments for type 2 diabetes’ in the last issue (Br J Cardiol 2009;16:163) may have given the impression that the National Institute for Health and Clinical Excellence (NICE) only suggested DPP4-inhibitors be considered in the third-line position (as an add-on metformin and sulphonylurea) for the treatment of type 2 diabetes. In fact, the guideline also recommended consideration in the second-line position as an alternative to sulphonylurea in patients at significant risk of hypoglycaemia or its consequences, or in patients at significant risk of hypoglycaemia or its consequences, or in patients intolerant of or contraindicated to sulphonylureas. Additionally, of the two DPP4-inhibitors currently available, only sitagliptin is licensed for third-line use.
Full details of the guidance (NICE short clinical guides 87) are available on line at: www.nice.org.uk/CG87.
Hypertension tool available based on national guidance
Software is now available to help primary care professionals make hypertension treatment decisions according to National Institute of Health and Clinical Excellence (NICE)/British Hypertension Society (BHS) guidance.
Key features of the program, which has been developed by the Department of Medicines Management at Keele University with the support of an unrestricted educational grant from Takeda, include: treatment and lifestyle recommendations based on NICE/BHS algorithms and guidance; visual aids and personalised materials to support patient discussion, such as a cardiovascular risk assessment. Patients can also take away a personal report summarising their consultation and can be tracked over subsequent clinic visits.
The software will be kept up-to-date by automatic on-line update. Healthcare professionals who would like a free
copy should contact Simon Thomas at Keele University by email: firstname.lastname@example.org or by phoning
Prasugrel recommended by NICE for appropriate patients
The National Institute for Health and Clinical Excellence (NICE) has published a Final Appraisal Determination (FAD) for prasugrel (Efient®).
This states that prasugrel in combination with aspirin is recommended as an option for preventing atherothrombotic events in patients with acute coronary syndrome (ACS) having percutaneous coronary intervention (PCI) only when: immediate PCI for ST-segment-elevation myocardial infarction (STEMI) is necessary; or stent thrombosis has occurred during clopidogrel treatment; or the patient has diabetes mellitus. People currently receiving prasugrel for treatment of acute coronary syndromes whose circumstances do not meet these criteria should have the option to continue therapy until they and their clinicians consider it appropriate to stop.
Patients who have experienced the most severe form of ACS are among those who will benefit from prasugrel. The NICE committee evaluated the cost-effectiveness of prasugrel based on data from the TRITON-TIMI 38 trial. It concluded that the advantage of the new drug over clopidogrel “was plausible” in all patients with STEMI and in all patients with diabetes.
The committee acknowledged that formulations of generic clopidogrel were nearing the market, and the price of clopidogrel would change once generic formulations were made available. It recommended that the guidance on prasugrel should therefore be reviewed in one year’s time when any substantial change to the nationally available price of clopidogrel could be considered.
Further information on the guidance can be found at www.nice.org.uk