Journals Watch - Stroke and cancers

Too busy to catch up on the research? Let Dr Raj Thakkar update you.

Thrombolysis with alteplase after acute ischaemic stroke N Engl J Med 2008; 359: 1,317-29
Acute cerebral events should be considered as a medical emergency and this was reiterated in the latest NICE guidelines on stroke and TIA.

In part, this is so patients may be considered for thrombolysis. Some centres, however, have ceased thrombolysing patients with acute ischaemic strokes because of adverse outcomes, mainly bleeding. This study looked at the use of alteplase in patients with acute stroke 3-4.5 hours after onset of symptoms.

Thrombolysis after acute ischaemic stroke reduces disability at 90 days if administered promptly

After CT, 821 appropriate patients were randomised to either alteplase 0.9mg/kg or placebo. The primary end-point was disability at 90 days. Other measures included death and symptomatic intracranial haemorrhage.

Median alteplase administration time was three hours 59 minutes. Alteplase conferred reduced disability and therefore a more favourable outcome compared with placebo (52.4 per cent versus 45.2 per cent; odds ratio, 1.34) although the 95 per cent confidence interval was very close to 1.00.

Alteplase, perhaps predictably, caused more intracranial haemorrhage than placebo (27.0 per cent versus 17.6 per cent) although mortality did not differ between the two groups.

Alteplase can reduce disability in selected patients; this study has reiterated how important it is that we, as GPs, treat acute stroke as urgently as we do an MI.

Combination therapy for urinary tract symptoms Mayo Clin Proc 2008; 83: 1,002-10
Lower urinary tract symptoms (LUTS) can significantly impact on our patients' quality of life. A quick, low-risk management strategy without having to refer to secondary care could provide an acceptable and cost-effective outcome.

In this study the researchers assessed whether extended-release oxybutynin conferred an additional benefit when combined with an alpha1-blocker (tamsulosin).

A total of 420 men over the age of 45 with LUTS were enrolled into this double-blind study and followed up for a 12-week period. They were randomised to receive tamsulosin combined with either extended-release oxybutynin 10mg or placebo.

A number of end-points were measured including post-void volume and flow rates, and International Prostate Symptom Score (IPSS). The combination of tamsulosin and oxybutynin significantly improved patients' IPSS score after eight and 12 weeks of treatment.

Residual volume comparisons were not statistically significant. Nevertheless, the authors suggest that combination therapy offers greater efficacy than tamsulosin monotherapy without adverse side-effects or compromising safety.

Intensive lipid lowering in aortic stenosis  N Engl J Med 2008; 359: 1,343-56
In the presence of ventricular dysfunction, aortic stenosis can have a poorer prognosis than many cancers. In addition to cardiac failure, aortic stenosis also increases the risk of cardiovascular events.

There has been some evidence that high lipid concentrations may increase the risk of aortic stenosis. Lipid lowering therapy may therefore reduce the gradient across the aortic valve and, intuitively, reduce the need for surgery and reduce morbidity and mortality.

This randomised controlled study aimed to show whether intensive lipid lowering therapy reduces the incidence of cardiovascular events/procedures globally, cardiac failure, the need for aortic valve surgery and procedures such as coronary bypass grafting or stenting.

A cohort of 1,873 patients with mild-to-moderate asymptomatic aortic stenosis were randomised to either simvastatin 40mg plus 10mg ezetimibe or placebo and followed up for over four years. There was no overall difference between the two groups in the global cardiovascular event rate or the need for aortic valve replacement.

Lipid lowering did reduce the number of ischaemic events but significantly increased the cancer rate (p=0.01).

More data are needed to establish whether there is a causal link between lipid lowering therapy and cancer. We should not, however, use these drugs to improve outcomes in patients with aortic stenosis unless there is another indication to do so.

The risk of breast cancer in BRCA1 mutation carriers J Natl Cancer Inst 2008 doi:10.1093/jnci/djn313
There has been much data recently on the affect of HRT on cardiovascular disease and cancer. Traditional teaching suggests HRT increases the risk of breast cancer, but what about the small percentage of patients who have the BRCA1 gene? This case-control study involved 472 postmenopausal women with the BRCA1 gene and aimed to discover whether HRT influenced their risk of breast cancer. Perhaps unexpectedly, HRT reduced the risk of breast cancer (OR 0.58, CI 0.35-0.96). This effect was shown to be estrogenic in origin.

The saga with HRT continues as the water becomes even muddier. More trials and clear protocols are required to guide doctors.

Wood dust exposure and the risk of cancers in males  Occup Environ Med 2008; 65: 647-54
This US study aimed to confirm whether wood dust does indeed increase the risk of cancers of the upper aero-digestive tract and respiratory cancers.

The case-control study involved more than 1,500 men with a variety of cancers (oral, oropharyngeal, nasal cavity, nasopharyngeal, hypopharyngeal, laryngeal, lung, tracheal, oesophagus and gastric cardia) and took into account smoking history.

Wood dust was found to increase the risk of the upper respiratory and digestive cancers by 32 per cent (OR 1.32, CI 1.01-1.77) and lung cancer by 69 per cent (OR 1.69, CI 1.20-2.36). Risk was particularly found in patients known to have been exposed to wood dust for more than 20 years.

Dust exposure was not found to be a risk factor for oesophageal and gastric cancers. Not surprisingly, the combination of wood dust exposure and smoking further increased the risk of cancer compared with those who had never smoked.

Dr Thakkar is a GP in Wooburn Green, Buckinghamshire, and a member of our team who regularly review journals.

The quick study

  • Thrombolysis with alteplase after acute stroke can reduce disability. Lower urinary tract symptoms may be improved by oxybutynin and tamsulosin combination therapy.
  • Lipid lowering reduced the number of ischaemic events but increased the risk of cancer in patients with aortic stenosis.
  • HRT reduced the risk of breast cancer in post-menopausal women with the BRCA1 gene.
  • Upper respiratory and digestive cancers were increased by occupational exposure to wood dust.

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