Clinical articles

Familial hypercholesterolaemia is a common genetic disorder that remains under-recognised. At present a simple genetic test is not available, although targeted genetic screening is being piloted in the UK. Recognition and treatment of this condition could help prevent many incidences of coronary heart disease. This article provides an overview of the pathophysiology, epidemiology, diagnosis and treatment of familial hypercholestrolaemia.

Low-density lipoprotein (LDL)-apheresis is the treatment of choice in homozygous familial hypercholesterolaemia as well as various other severe dyslipidaemic conditions. However, it appears to be under utilised in the UK. This article reviews the recent advances in (LDL)-apheresis techniques, as well as the beneficial effects and clinical outcomes of this therapeutic modality.

Anticoagulant therapy plays a key role in pharmacological reperfusion therapy for acute ST segment elevation myocardial infarction (STEMI). Until recently, the established role of unfractionated heparin (UFH) was unquestioned, but large trials with new agents including factor Xa inhibitors, direct thrombin inhibitors, and in particular, low molecular weight heparins (LMWHs), have shown potential advantages compared with UFH. This paper reviews the evidence base for the newer anticoagulants, with a focus on LMWH including the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment – Thrombolysis in Myocardial Infarction (ExTRACT TIMI)-25 study, which found that enoxaparin when appropriately adjusted for weight, age and renal function, provided superior net clinical benefit (balancing efficacy and safety) compared with UFH. In addition, new data from higher risk subgroups (the elderly, those with renal dysfunction or undergoing early coronary intervention) and the efficacy and safety of using concurrent clopidogrel are discussed to illustrate how these data may be integrated into contemporary practice.

Data from 101 practices that had completed a survey of cholesterol target achievement using rosuvastatin in routine general practice were pooled to assess effectiveness at a national level. A total of 10,396 patients, who had total cholesterol (TC) measured prior to, and on, rosuvastatin 10 mg daily, were included in the analysis. Of these, 6,375 patients had not received a statin prior to rosuvastatin. The remainder had been switched from another statin.

Significant reductions were observed in TC (28%) and low-density lipoprotein cholesterol (40%) when comparing prior to and on rosuvastatin 10 mg (p<0.001). A significantly greater proportion of patients achieved the General Medical Services (GMS) Quality and Outcomes Framework (QOF) target of TC ≤5 mmol/L with rosuvastatin 10 mg compared with prior to rosuvastatin (81% vs. 19%; p<0.0001). Of the 580 patients who had failed to reach target on atorvastatin 10 mg daily, 70% reached target on rosuvastatin 10 mg. Similarly, 68% of 246 patients who had failed to reach target on simvastatin 40 mg daily reached target on rosuvastatin 10 mg.

General practitioners across the UK also substantially achieved other national and international cholesterol targets in patients treated with rosuvastatin 10 mg, including second line to simvastatin 40 mg and where higher doses of other statins had failed to reach target.

The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) showed that addition of eplerenone to optimal medical therapy reduced morbidity and mortality in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. This international study also showed that the addition of eplerenone reduced the number and duration of rehospitalisations for heart failure. A budget impact model has been developed to estimate the effect of adding eplerenone to standard care in the UK. The model is based on the results of the EPHESUS study, UK epidemiological data, UK drug acquisition costs and National Health Service (NHS) hospital in-patient costs and average length of stay for England. All costs are expressed in pounds sterling.

It estimates the incremental costs and benefits of adding eplerenone to standard care in heart failure resulting from myocardial infarction, from the perspective of NHS healthcare decision makers over a three-year period.

The model shows that if all eligible patients are treated with eplerenone the estimated cost per life year saved is £6,730 in year three. In a primary care trust with a population of 250,000, this level of treatment results in a reduction of 46 bed days for rehospitalisations due to heart failure, at a cost per bed day avoided of £1,469. With hospital in-patient care the biggest single healthcare cost in heart failure, reduction in hospitalisation is a key priority within the NHS in the UK. Models such as the one described here enable the budgetary consequences of using a new drug to be identified and clarify the role of drug treatment in delivering NHS priorities.

Achieving a lower heart rate is important in treating angina. Established approaches include the use of beta blockers and certain calcium channel blockers. However, the use of these drugs may be limited by side effects or contraindications. Ivabradine (Procoralan®) is a novel agent that lowers heart rate through selective I(f) channel inhibition, acting specifically on the sinus node. We present a consecutive series of 30 patients initiated on ivabradine, within a district general hospital (DGH) setting. The aim of this study was to identify the heart rate-lowering and symptom-control properties of ivabradine, while monitoring adverse effects. Heart rate was measured on a baseline electrocardiogram (ECG) prior to starting ivabradine, and then within a 12-month follow-up period. The results identified a mean (standard deviation) 10 (14) beats per minute (bpm) decrease achieved on ivabradine (p<0.001), with greatest reduction in heart rate in those with a resting heart rate over 80 bpm prior to starting treatment (p<0.05), and in patients on a 5 mg twice-daily dosing regimen at follow-up (p<0.05). In parallel, the majority of patients reported favourable symptom benefit (21/30), and low rate of adverse events with discontinuation rate of only 2/30 felt directly related to the drug itself. We believe this to be the first report of using this novel drug in a ‘real-world’ DGH setting. The findings add confidence in using this anti-anginal agent in appropriate patients, and furthermore support conducting studies involving multiple centres, to further define and assess ivabradine in the clinical setting of angina.

A 63-year-old gentleman presented with palpitations and a sensation of chest fullness. He had previously undergone laparoscopic oesophageal fundoplication.

Dextrocardia is a rare anomaly with an estimated prevalence of about one in 10,000. The incidence of coronary artery disease is the same as in the general population. We report two cases of successful percutaneous treatment of coronary stenoses and aim to highlight some of the additional technical challenges that such patients present to the Interventional Cardiologist.

A 60-year-old male was admitted acutely unwell with prolonged ischaemic chest pain. Seven weeks earlier he had undergone percutaneous coronary intervention (PCI) following admission with an acute coronary syndrome (ACS). Two paclitaxel-eluting stents to his left anterior descending (LAD) artery (2.75 x 32 mm, 2.75 x 16 mm), a 3 x 12 mm Tecnic stent to his obtuse marginal artery and 3.5 x 9 mm Tecnic stent to his proximal circumflex artery were inserted. The patient received intravenous heparin plus abciximab and an excellent angiographic result was achieved (figure 1A). He was discharged home on six months’ dual antiplatelet therapy.

Although cardiac electrostimulation was recognised centuries ago, the technology of implantable heart rhythm monitoring and therapeutic devices has only been established in the last few decades. Recent advances in such technology have led to simpler implantation techniques, greater patient convenience with smaller device sizes, extended battery longevity, increased device safety and reliability, and improved clinical outcomes.