Clinical articles

NAUTILUS (The multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL cholesterol) was an open label, uncontrolled, phase IIIb study. The study population included a total of 566 patients with dyslipidaemia and low high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L [< 40 mg/dL] in men and < 1.2 mmol/L [< 46 mg/dL] in women) who were inadequately controlled by diet alone. Patients received once-daily treatment with prolonged release nicotinic acid (Niaspan^{®; target dose 2,000 mg/day), added to existing regimens for 15 weeks. At baseline, 40.5% of patients were receiving an HMG-CoA reductase inhibitor (statin), mostly simvastatin or atorvastatin.}

Patients taking and not taking concomitant statin therapy reported a similar incidence of all-cause adverse events (AE) of 64.6% vs. 57.9%, respectively, treatment- related AE (54.6% vs. 47.2%), all-cause serious AE (3.9% vs. 3.6%), treatment-related serious AE (0.9% vs. 0.3%), and withdrawals for AE (17.5% in each group). The incidence of flushing was similar in patients with and without statin treatment (45.0% vs. 40.1%), as was the proportion of patients withdrawing because of flushing (8.7% vs. 10.4%). Only about one quarter of patients flushed more than five times. There was no sign of serious hepatic or muscle toxicity. The addition of prolonged-release nicotinic acid markedly raised HDL cholesterol levels irrespective of statin treatment; it was well tolerated and effective when combined with a statin in patients with dyslipidaemia.

Older patients are often at high risk for cardiovascular disease. Low high-density lipoprotein (HDL) cholesterol is an independent risk factor for cardiovascular disease. Prolonged-release nicotinic acid (Niaspan^®) is a once-daily formulation of nicotinic acid with improved tolerability compared with the immediate-release formulation. It may be used to correct low levels of HDL cholesterol. NAUTILUS (the multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL cholesterol) evaluated prolonged-release nicotinic acid at doses of up to 2,000 mg/day once daily in 566 patients, of whom 33.6% were aged > 65 years.

A similar incidence of adverse events (AE) was observed following 15 weeks of prolonged-release nicotinic acid treatment in older vs. younger patients for all-cause AE (55.3% vs. 63.3%) and for treatment-related AE (46.3% vs. 52.1%). Most AE were related to flushing, which also occurred at similar frequency in older and younger patients (39.5% vs. 43.4%).

Gastrointestinal AE were the most common AE apart from flushing, and occurred in 12.1% of older patients and 14.4% of younger patients. Serious AE were uncommon. There was no hepatotoxicity or serious muscle toxicity. Marked improvements in indices of atherogenic dyslipidaemia were observed (increases from baseline in HDL cholesterol of 26% in older and 21% in younger patients and decreases in triglycerides of 16% and 9%, respectively).

Prolonged-release nicotinic acid is well tolerated and effective in older patients, and is suitable for correction of low HDL cholesterol in this population.

Heart failure has a comparable prognosis to many cancers and accounts for approximately 4% of deaths in the UK. Despite its poor prognosis, few patients have access to specialist palliative care services. The National Institute for Health and Clinical Excellence (NICE) acknowledges that the palliative care needs of patients with heart failure and their informal carers are not currently being met. Its recently published guidance recommends the development of an effective multidisciplinary service model for such patients.

Thrombolytic therapy in the management of acute myocardial infarction (MI) shows true evidence of benefit. Administration of a thrombolytic saves about 30 lives per 1,000 in those presenting within six hours of symptom onset but only 20 lives per 1,000 when patients receive treatment between six and 12 hours after symptom onset. After 12 hours there appears to be only a small and statistically uncertain benefit.

The aim in thrombolysis should be to increase the number of patients who achieve TIMI grade 3 flow as soon as possible after the occlusive event. Additional benefit in improving thrombolysis, particularly in reducing 30-day mortality, has been shown by adding the antiplatelet agent, aspirin, to thrombolytic therapy. The addition of a second antiplatelet agent, such as clopidogrel, has been shown to be of benefit in other, less immediately severe atherothrombotic manifestations (unstable angina and non-ST-elevation MI) and looks to be a promising development in the management of acute ST-elevation MI. The potential advantages of dual antiplatelet therapy in this setting, investigated in the recently published CLARITY study, are discussed.

A 75-year-old gentleman presented to his general practitioner with palpitations and dizziness. A 24-hour Holter monitor confirmed the diagnosis of paroxysmal sustained atrial flutter and episodes of less organised rhythm, that were thought to be atrial fibrillation. His symptoms failed to improve on combination treatment with digoxin and bisoprolol. He was referred for flutter ablation. Our aim was to replace the above pharmacological agents with a class 1C drug. The patient was not taking warfarin. A transoesophageal echocardiogram (TOE) was therefore arranged to exclude left atrial thrombus, prior to performing the ablation.

In 1993, a 61-year-old man underwent balloon angioplasty to the left anterior descending artery (LAD) after an anterior myocardial infarction. Repeat angiography in 1997 after a recurrence of symptoms revealed a severe proximal LAD stenosis, and this was again treated by balloon angioplasty. Two months later, the LAD had occluded and a 16 mm bare stainless steel stent (Nir®) was implanted with a 3 mm balloon (figure 1). Four months afterwards, angiography revealed severe in-stent restenosis (figure 2) and he was referred for coronary artery bypass grafting; the left internal mammary artery (LIMA) was grafted to the LAD.

He remained symptom-free for six years until 2004, when his angina recurred. Repeat coronary angiography demonstrated spontaneous regression of the previously stenosed LAD stent, which was now widely patent (figure 3). The LIMA graft had involuted. A new stenosis in a large obtuse marginal branch was treated with a drug-eluting stent.

This article describes the evaluation of a new postgraduate diploma in cardiology course run by the Bradford City Teaching Primary Care Trust.

Heart failure is a common condition, characterised by poor prognosis. Despite evidence that effective treatment improves symptoms and prognosis, management remains sub-optimal. General practitioners (GPs) have a key role in the assessment and treatment of patients with heart failure. This study was designed to ascertain the knowledge and attitude of GPs towards the management of heart failure.

Anonymised questionnaires were sent to 355 GPs in the Nottingham area in May 2003 and 227 (64%) responded. The mean (standard deviation) age of respondents was 45 (7) years and they had been in general practice for 15 (7.6) years. The questionnaires found that 223/227 (98%) of GPs were aware that angiotensin- converting enzyme (ACE) inhibitors have been shown in clinical trials to reduce mortality in heart failure; 155/224 (69%) were aware that beta blockers reduced mortality in heart failure; 53/225 (23.3%) believed diuretics improved prognosis. Almost 60% routinely initiated ACE inhibitors but 26% expressed concerns about their side effects and so were less likely to initiate this treatment.

Most GPs seemed able to manage heart failure effectively and ACE inhibitor prescription for patients with chronic heart failure (CHF) is now well established within primary care. Knowledge and prescription rates for the remaining effective therapies remain low.

Miniaturisation of machines has allowed echocardiography to be performed in the community as well as anywhere in the hospital. It has led to an expansion of the types of study performed: ultrasonic stethoscope, screening and focused studies, and standard echocardiograms. In expert hands, results compare favourably with standard studies on full systems. With focused studies, abnormalities may be missed in areas of the heart that are not imaged. For screening studies, the negative predictive accuracy is high while the positive predictive accuracy is lower.

Portable echocardiography can save time and costs, but it is essential that studies are requested and performed within a tightly controlled clinical setting. Operators should be trained appropriately and be part of a broad echocardiography service that includes quality control, continuing education and expert supervision.

Familial hypercholesterolaemia (FH) affects about one in 500 in the UK population. There are no symptoms or signs of raised cholesterol in children and so individuals can only be identified by screening, usually as a ‘cascade’ from known probands. Once identified, such children should be treated to prevent premature atherosclerosis.