2002, Volume 09, Issue 08, pages 425-492

Biotechnology and cardiovascular medicine – a hazy past and bright future? Melinda Swann, Adam Raman, Michael KirchengastFrom such successful beginnings, the biotechnology sector has since gone on to have a rather hazy past, for which there are many plausible explanations. In March 2000, the sector was grossly overvalued and, since then, investors’ aversion to the area has flourished due to the perceived risk they felt they were taking. This has led to the growth of many biotechnology companies being stunted since access to capital has become more difficult – studies, especially long-term survival trials in cardiovascular medicine.

The Impact of Nicorandil in Angina (IONA) study A report from a British Cardiac Society Satellite Symposium, 2002 Angina pectoris is not a benign disease: it is associated with significant morbidity and mortality and it affects more than 10% of men over the age of 60 years.

This study looks at how well cardiovascular risk factors were being controlled in a high-risk group of patients awaiting coronary artery bypass surgery. It shows significant short falls in the implementation of currently advocated strategies.

This article explains how general practitioners can diagnose and treat heart failure in primary care. Diagnosis is difficult and four diagnostic tests – the electrocardiogram, chest x-ray, blood test for natriuretic peptides and echocardiography – are recommended as being of particular value in confirming the diagnosis in primary care.
A six-step treatment strategy is then given advising i) confirming the diagnosis, ii) excluding other treatable causes of heart failure, iii) giving general advice to the patient, iv) starting treatment with a diuretic, v) then adding an angiotensin-converting enzyme inhibitor, and, vi) finally adding a beta blocker. A 10-point plan explaining in detail how to start beta blockers in primary care concludes the article.

Pleuritic chest pain and hypoxia – a diagnostic dilemma Sanjiv Mahadeva, Pulak Sahay, Richard V Lewis Pulmonary thromboembolism (PE) is notoriously difficult to diagnose since it commonly presents in a non-specific manner. Only 15–30% of the patients identified at post-mortem as having a massive PE have been diagnosed correctly prior to death.1,2 However, large studies have shown that certain clinical symptoms and features such as dyspnoea, tachypnoea, pleuritic chest pain with a normal chest radiograph and a low PaO2 are present in more than 90% of patients with PE.2 Clinicians in a district hospital setting have to rely on these features, especially when facilities for detailed imaging such as computerised tomography (CT) or pulmonary angiography are not available. Occasionally, certain other diseases can mimic the clinical picture of PE and lead to delay in instituting appropriate treatment. We present two patients with symptoms and clinical investigations which were highly suggestive of acute PE but who turned out to have very different diagnoses in the end.

A new extended-release (XL) formulation of fluvastatin has been developed for once daily treatment of primary hypercholesterolaemia. This study was designed to determine the safety and effect of fluvastatin XL 80 mg on a range of lipid parameters compared with the immediate-release (IR) formulation of fluvastatin 40 mg. In a multicentre, double-blind study, 555 patients with primary hypercholesterolaemia (Fredrickson types IIa or IIb) were randomised to 24 weeks treatment with fluvastatin XL 80 mg or IR 40 mg, each given once daily at bedtime. The study found the least square mean reduction in LDL-C after 24 weeks treatment was 32.6% in the fluvastatin XL 80 mg group (n=312) and 23.9% in the fluvastatin IR 40 mg group (n=165), an 8.7% between-treatment difference (95% confidence interval: 6.5%, 10.9%) in favour of the XL formulation (p<0.001). A higher proportion of patients in the fluvastatin XL 80 mg group achieved ≥ 35% reductions in low-density lipoprotein cholesterol (42.3% vs. 13.3%). High-density lipoprotein cholesterol levels were increased by 9.1% and 7.0%, respectively in the XL and IR groups; median triglyceride levels fell by 19% and 13%, respectively. Tolerability was comparable in the two groups, and there were no laboratory safety concerns. The study concluded that fluvastatin XL 80 mg once daily is safe as a starting dose and effectively lowers low-density lipoprotein cholesterol and triglyceride levels in patients with primary hypercholesterolaemia.

This study investigated the effect of orlistat on weight loss and serum lipid parameters in obese patients with hypercholesterolaemia. A total of 215 adult obese patients (body mass index ≥30 kg/m2) with hypercholesterolaemia (total plasma cholesterol ≥6.5 mmol/L or plasma low density lipoprotein cholesterol ≥4.2 mmol/L) were recruited for screening at 12 out-patient clinics in the UK. Of these, 142 patients were randomised to receive double-blind treatment for 24 weeks with orlistat 120 mg (n=71) or placebo (n=71) three times daily in combination with a mildly hypocaloric diet. Patients completing the double-blind phase (orlistat n=42, placebo n=55) were eligible to enter a further 28-week open-label phase and received orlistat 120 mg three times daily in combination with the hypocaloric diet. Mean weight loss after 24 weeks was 4.4 kg (4.4%) in the orlistat group vs. 2.6 kg (2.5%) with placebo (p<0.01). At the end of the double-blind phase, 44.0% of orlistat-treated patients vs. 18.0% of placebo recipients had lost ≥5% of their initial body weight (p<0.001), and 7.6% vs. 4.2% had lost ≥10% (p=NS). Patients who continued on orlistat during the open-label phase had a mean weight loss of 4.97 kg (4.86%) after 52 weeks. Patients who switched to orlistat had a mean weight loss of 4.28 kg (4.23%). Orlistat was associated with significantly greater reductions than placebo in plasma total cholesterol (-10.88 + 1.36% vs. -3.25 + 1.33%; p<0.001) and LDL-cholesterol (-14.14 + 2.68% vs. -3.68 + 3.61%; p<0.05) during the double-blind phase. Despite similar weight loss at the end of the 52-week period, patients who remained on orlistat throughout the study had greater improvements in plasma lipid concentrations than patients who switched to orlistat after 24 weeks. Orlistat, in combination with a mildly hypocaloric diet, promotes clinically meaningful weight loss and improvements in lipid concentrations in obese patients with hypercholesterolaemia.

Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiovascular disorder with a prevalence of one in 500 in the general population. It is believed to be a disease of the cardiac sarcomere and is caused by a variety of mutations in genes responsible for sarcomeric contractile proteins. It is characterised macroscopically by myocardial hypertrophy and microscopically by myocyte fibrosis and disarray. Most patients tend to present with functional limitation and symptoms such as palpitation, chest pain or syncope. The underlying mechanisms involved are complex, multiple and not yet fully understood. Further clarification of these mechanisms may enable improvements in current symptom control or the development of new avenues of therapy. A small but significant proportion of patients suffer sudden cardiac death and this can be the initial presentation of the condition. In fact, HCM is the commonest cause of sudden death among individuals below the age of 30 years. The identification of this high-risk cohort remains the most important aspect of HCM management, particularly in light of growing evidence of the effectiveness of prophylactic strategies.

THE CHOLESTEROL MANAGEMENT DEBATES ESC debate Motion 1: "This house believes that lowering current cholesterol targets will have additional benefits to CV risk management" Motion 2: "This house believes that the benefits of raising HDL warrant its introduction as another lipid variable to target." The lower the better. The real benefits of lowering cholesterol even further The Atlantic divide in coronary prevention PCCS debate Motion 1: "This house believes that current government policy is leading to the erosion of clinical judgement, exemplified by the CHD National Service Framework." Motion 2: "This house believes that optimal management of cholesterol is a relief, not a burden." The National Service Framework for CHD – Big Brother or helpful guide? A stitch in time – counting the cost of optimal CHD prevention