News Forum

GPs with an interest in cardiovascular disease review papers of significance from research teams across the world.

Clopidogrel dosing for patients having PCI
Immediate angioplasty after thrombolysis
VTE risk in the acute hospital care setting
Aspirin sensitivity in patients having PCI
Treating patients with type-2 diabetes
LDL cholesterol and the development of CHD
GP and patient beliefs about causes of obesity

Clopidogrel dosing for patients having PCI
Angiolillo DJ, Costa MA, Shoemaker SB et al. Am J Cardiol 2008; 101: 440-5
Patients who undergo percutaneous coronary intervention (PCI) are prescribed clopidogrel to reduce their risk of stent thrombosis. Recent guidelines have advocated increasing the dose of clopidogrel from the standard 75mg to 150mg/day in high-risk patients (defined as those achieving less than 50 per cent platelet inhibition).
It is known that patients with diabetes are more resistant to the effects of clopidogrel than age-matched non-diabetics. As such, patients from the Optimising Anti-Platelet Therapy in Diabetes Mellitus (OPTIMUS) trial participated in this study.
Using assays, platelet inhibition increased by more than 13 per cent with the higher dose of clopidogrel, although the degree of inhibition was variable. Further work with real endpoint data may be required to demonstrate an advantage in all patients with diabetes who have undergone PCI. Although the cost implications of increased clopidogrel prescribing may be far reaching, it may prove highly cost-effective in the long term.
Dr Raj Thakkar is a GP in Wooburn Green, Buckinghamshire, and a hospital practitioner in echocardiography at Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust


Immediate angioplasty after thrombolysis
Di Mario C, Dudek D, Piscione F et al. Lancet 2007; 371: 559-68
In an ideal world, patients who experience acute ST-elevation MI (STEMI) will be treated by primary angioplasty.
Delayed health-seeking behaviour, poor access and lack of resources may act to prevent a patient from receiving definitive treatment. Once the 90-minute window of opportunity has passed, thrombolysis is the treatment of choice. Guidelines on short-term management beyond thrombolysis are lacking.
The CARESS-in-AMI trial aimed to address this question by randomising patients with STEMI who had been treated with combined abciximab and reteplase to transfer for percutaneous coronary intervention (PCI) or standard medical therapy.
Six hundred patients under the age of 75 years were included in this open prospective European study. The outcome measures included death, reinfarction or refractory ischaemia at 30 days post-MI.
Patients who received immediate PCI were significantly less likely to experience an adverse health outcome (13), compared with 32 in the standard medical therapy group.
Resources are required to educate patients to seek help early when experiencing symptoms consistent with MI and to fund facilities to provide a robust PCI service. RT


VTE risk in the acute hospital care setting
Cohen AT, Tapson VF, Bergmann J-F et al. Lancet 2008; 371: 387-94
Pulmonary emobolism (PE) accounts for 5-10 per cent of deaths in hospitalised patients. Although DVT is found in nearly 50 per cent of patients with PE, a high proportion of patients have no symptoms of DVT.
In this study, researchers investigated the risk prevalence of venous thromboembolism in the acute hospital care setting and tried to determine the proportion of at-risk patients who receive effective prophylaxis. They studied 68,183 patients from 32 countries and six continents.
They report that in the UK, 37 per cent of at-risk medical patients and 74 per cent of at-risk surgical patients received the prophylaxis recommended by the American College of Chest Physicians. Practice-based commissioners working on care pathways for community-based DVT diagnosis using D-dimers and primary care access to Dopplers should ask acute trusts about protocols for preventing DVT, especially in medical and elderly care patients. An audit of DVT prophylaxis in patients with congestive cardiac failure is a good place to start.
Dr Vasa Gnanapragasam is a GP with an interest in cardiology in Sutton, Surrey


Aspirin sensitivity in patients having PCI
Rossini R, Angiolillo DJ, Musumeci G et al. Am J Cardiol 2008; 101: 786-9
Aspirin alone, or in combination with clopidogrel, is the antiplatelet treatment of choice for the management of atherothrombotic vascular disease. Aspirin-allergic patients who require percutaneous coronary intervention (PCI) may benefit from a rapid desensitisation protocol that allows them to overcome this problem.
From October 2005 to September 2006, 1,014 consecutive patients requiring coronary angiography were studied. Of these, 26 had aspirin sensitivity, either through respiratory (asthma and/or rhinitis) or cutaneous (urticaria and/or angioedema) manifestations. None of the patients had previously had an anaphylactic reaction.
These patients were commenced on a novel desensitisation protocol, involving incremental doses of aspirin (1mg, 5mg, 10mg, 20mg, 40mg and 100mg) given over a 5.5-hour period, without pre-treatment with antihistamines or corticosteroids.
The procedure was performed before angiography in all cases except those requiring primary PCI, in whom it was performed before discharge. The protocol was immediately successful in 23 out of 26 patients and continued to be successful through to one year of follow-up in all but one patient, who developed a peptic ulcer. The authors have demonstrated a safe and practical way of overcoming aspirin sensitivity under controlled conditions in patients with coronary artery disease who require effective antiplatelet therapy.
- Dr Aung Myat, specialist registrar in cardiology, United Lincolnshire Hospitals NHS Trust


Treating patients with type-2 diabetes
Goede P, Lund-Andersen H, Parving HH, Pedersen O. N Engl J Med 2008; 358: 580-91
The landmark Diabetes Control and Complications Trial confirmed that better glycaemic control reduces the risk of diabetic retinopathy, nephropathy and neuropathy.
This paper refers to a relatively small study of 160 patients with diabetes and microalbuminuria. The authors compared deaths from any cause and from cardiovascular causes in patients randomised to intensive and conventional therapy.
The intensive therapy group was assigned a target HBA1C of <6.5 per cent, fasting cholesterol of <4.5 mmol/L, fasting serum triglyceride level of <1.7mmol/L and BP of <130/80mmHg. In this group, deaths from cardiovascular causes and any cause were reduced.
The most striking figure from this study was that 50 per cent of the 80 patients in the conventional therapy group died during the follow-up period, whereas only 24 of the 80 patients in the intensive group died. Will studies like this influence changes to the nGMS targets? VG


LDL cholesterol and the development of CHD
Sandhu MS, Waterworth DM, Debenham SL et al. Lancet 2008; 371: 483-91
LDL cholesterol is known to have a causal association with the development and propagation of CHD. The authors of this study set out to find novel genetic determinants of variation in LDL concentrations that would offer greater understanding of its metabolism and regulation.
In total, more than 16,000 white European men and women, including replication studies, were genotyped from six independent populations in the UK and Switzerland. Standard lipid profiles were also derived from study participants.
The authors demonstrated a gene locus associated with LDL concentration on chromosome 1p13.3 through the identification of three single nucleotide polymorphisms located there.
Genetic variants at this locus were able to explain about 1 per cent of the variation in LDL concentration. Other studies have shown this locus to have a statistical association with CHD, enhancing the link between cholesterol levels and CHD.

The investigators now plan to test whether this association is found in non-European populations from Africa and Asia. They will refine the signal to determine whether the locus could explain certain phenotypes, such as familial hypercholesterolaemia. Gene therapy is soon to reach our shores, so these results might help to identify novel therapeutic targets for CHD. AM


GP and patient beliefs about causes of obesity
Ogden J, Flanagan Z. Patient Educ Couns 2008; 71: 72-8
GPs play an increasingly important part in achieving sustainable weight reduction in obese patients. Success rates, however, remain poor. Research has shown that to some extent, this failure can be attributed to a negative attitude held by GPs regarding their own role in obesity management.
These authors explored this phenomenon through a questionnaire-based study dealing with causes of, and solutions to, the problem of obesity. The study compared the opinions of 73 GPs with those of 311 lay people.
There was a significant mismatch between the beliefs of GPs, who held to a more behavioural model of obesity, and those of lay people, who endorsed a more biological approach.
This meant the GPs were ambivalent about medication, surgery, counselling, policy changes and seeing the GP to treat obesity. They were often reluctant to refer patients for further treatment. In essence, there is mounting evidence to suggest that GPs do not believe obesity belongs in the medical domain.
The authors believe that too much emphasis is being put on coherence, whereby a given solution must tie in with a preordained cause; this underestimates the potential contribution of solutions that do not directly address the cause. They advise GPs to change their beliefs or consider whether solutions need always address causality. AM.

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