The Food and Drugs Administration has updated prescribing information for the contraceptive patch (EVRA®) after studies found an increased risk of venous thromboembolism (VTE) when compared to combined oral contraceptive tablets (COCs).
According to information on the manufacturers website there have been four epidemiological studies comparing the patch to oral contraceptives. Two of these studies found no difference in risk while two have found an approximate doubling of risk.
The Summary of Product Characteristics (SPC) available in the UK states that, "currently there is no evidence to exclude that EVRA may be more thrombogenic than combined oral contraceptives". The SPC also states that this product should not be used in patients with a history of venous thromboembolism.
Action: When discussing contraceptive options, clinicians should ensure that patients are made aware of the increased risk of VTE with EVRA compared to COCs.
Addiction has published the results of a study comparing the effectiveness of varenicline with nicotine replacement for smoking cessation. The study also evaluated the safety and efficacy of varenicline in people with mental illness.
The study was conducted in a tobacco dependence clinic operated by the NHS and involved 412 patients. 208 received varenicline and 204 received NRT in addition to routine care including support sessions. There is no indication that the study was randomised or blinded.
The results of the study found a higher 4-week quit rate (72.1% with varenicline, 61.3% with NRT, difference 10.8% [95% CI 1.8% to 19.9%]). Significantly more patients in the varenicline group experienced side effects including nausea, disturbed sleep, vivid dreams, drowsiness and low mood/depression.
Varenicline has been reviewed by the National Institute for Health and Clinical Excellence (NICE) and has also been the subject of a safety review conducted by the Medicines Healthcare products Regulatory Agency (MHRA) in conjunction with the European authorities.
Action: Clinicians should follow current NICE and MHRA guidance. Varenicline is an option along with nicotine replacement therapy and bupropion, but its use should be avoided in patients with underlying mental illness.
Adapted from an article on the NPCi blog.
The British Medical Journal has published the results of a study that has linked calcium supplementation to an increased risk of cardiovascular events. This study has been widely reported in the media: BBC, The Times. It has also been covered on the NPCi blog and NHS Behind the Headlines article.
The study was a secondary analysis of a randomised placebo controlled trial involving 1,472 post-menopausal women. Patients were given 1,000mg of elemental calcium as citrate salt or matching placebo. Data were collected over five years for cardiovascular outcomes including death, myocardial infarction, angina, other chest pain, stroke and transient ischaemic attack. This was a secondary analysis of a study that was originally designed to assess the effects of calcium on bone density and fracture incidence.
The study found an increased risk of myocardial infarction (45 events versus 19 events, P=0.0099, RR 2.24 [95% CI 1.20 to 4.17]) and an increased risk in a composite end point of myocardial infarction, stroke, or sudden death (101 events versus 54 events, P=0.0075, RR 1.66 [95% CI 1.15 to 2.40]).
The study is open to some criticism however:
- Calcium supplementation did not include Vitamin D which is routine practice in the UK
- More patients in the calcium arm smoked at baseline (3.4% versus 2.6%)
- More patients in the calcium arm were former smokers at baseline (40.3% versus 37.2%)
- Events were self reported by patients, when these were verified a smaller number of events were confirmed
- It is a reasonably small population to follow up for 5 years
- It is a secondary analysis of a trial originally designed and powered to answer another question
The NPCi blog concludes that the decision to prescribe a calcium and vitamin D supplement should "take into account the patient's risk of CV disease and osteoporosis. Calcium supplementation alone should not generally be prescribed to postmenopausal women for fracture prevention".
Action: Clinicians should be aware of this study and the media coverage. The information and articles above will provide sufficient information to allow clinicians to discuss this topic with worried patients.
The results (login required) of the ENHANCE Study have found no significant difference between ezetimibe and simvastatin compared to simvastatin alone in patients with heterozygous familial hypercholesterolemia.
The results of this study were due to be presented later this year at a meeting of the American College of Cardiology but many of the results are already available in an attempt to "end speculation about the results of the study" according to the manufacturers.
The study recruited 720 patients with heterozygous familial hypercholesterolemia and randomised them to treatment with ezetimibe and simvastatin or simvastatin alone for a period of 2 years. The primary end point was the mean change in the intima media thickness as measured at three sites in the carotid arteries.
There was no statistical difference in the primary outcome, the components of the primary outcome or the secondary imaging end points. There were also no differences in cardiovascular event outcomes although the trial was not powered to assess these outcomes. Additional long-term cardiovascular outcome studies are on going but are not due for completion until 2011.
Action: Clinicians should be aware of this negative study. Current recommendations still apply, simvastatin 40mg remains first line and monotherapy with atorvastatin remains a suitable second line in patients who fail to reach the national cholesterol targets of 5mmol/L for total cholesterol or 3mmol/L for low-density lipoprotein (LDL-C).
The British Medical Journal (BMJ) has published several articles discussing approaches to preventing falls and fractures. Fiona Godlee, editor of the BMJ sets the articles in context in Editor's Choice by requesting that risk reductions are expressed as absolute reductions rather than relative reductions.
A research article that aimed to systematically review the evidence supporting multifactorial assessments and interventions to prevent falls examined data from 19 studies of variable quality. There was a trend to a lower fall risk but the result was not significant. Additionally, there were no differences in rates of admission to hospital, emergency department attendance or death.
The authors state that, "any benefits from this type of intervention might be smaller than previously supposed" however due to the limited quality of the studies it remains difficult to assess the impact of these interventions on the number of falls and fall related injuries. More large scale, high quality randomised controlled trials are required.
This edition also contains two analysis articles. The first discusses changing the focus of fracture prevention to fall prevention rather than treating bone mineral density and the second examines the evidence for treating bone mineral density at osteopenic levels rather than waiting for osteoporosis.
The first article notes the unreliable nature of bone densitometry and the fact that over 80% of low trauma fractures occur in people who do not have osteoporosis. The authors recommend that fracture prevention should focus upon prevention of falls rather than treatment of bone density since falling is the strongest risk factor for fractures and not osteoporosis.
The second article questions the marketing of drug treatments to reduce the risk of fracture in women with osteopenia. It is argued that the rationale for this position comes from questionable post-hoc analyses that overstate the benefits and downplay the side effects. It is recommended that treatment decisions are based on an assessment of the absolute risk of fracture. As fracture risk increases with age and falls it would seem that treating postmenopausal women based on the presence of osteopenia alone is inappropriate.
Action: Clinicians who are endeavouring to reduce rates of hip fracture will find these articles a useful summary of the current evidence. Interventions should target absolute fracture risk and include assessment and reduction of falls risk.