Prescribing Advice for GPs

Ivabradine in Heart Failure?

August 31, 2010 at 9:29 am | In Prescribing Extra - Drugs |  Print | No Comments

The Lancet has published the results of the SHIFT study which aimed to assess the effect of heart rate reduction using ivabradine (Procoralan^®) in patients with heart failure. The results of this study have been reported in the general media (BBC).

The study recruited and treated 6,505 participants in symptomatic heart failure (NYHA II-IV) with an ejection fraction of 35% or less. They were all in sinus rhythm with a pulse rate of at least 70 beats per minute. Participants were on stable background treatment which included a beta-blocker, if tolerated. Treatment was randomly assigned to ivabradine titrated to a maximum of 7·5 mg twice daily or matching placebo.

The primary outcome of the study was a composite of cardiovascular death or hospital admission for worsening heart failure. Mean follow up was 22.9 months.

793/3,241 (24%) patients in the ivabradine group and 937/3,264 (29%) of those taking placebo had a primary endpoint event (HR 0·82, 95% CI 0·75-0·90, p<0·0001, NNT ~24). The difference was mainly driven by a reductions in the rate of hospital admission for heart failure (21% with placebo versus 16% with ivabradine, HR 0·74, 0·66-0·83; p<0·0001, NNT ~21) and death due to heart failure (5% with placebo versus 3% with ivabradine, HR 0·74, 0·58-0·94, p=0·014, NNT ~88). A greater number of patients treated with ivabradine reported bradycardia (5% versus 1%) and visual disturbances (3% versus 1%).

The authors of the study conclude that, “our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure “. However, an editorial in the same issue of the Lancet and the British Heart Foundation both call for further research to assess the place in therapy for ivabradine.

It should be noted that ivabradine is not currently licensed for use in heart failure and that at the current cost of £39.00 for 28 days of treatment it would cost approximately £84,000 to treat 88 patient in order to prevent one death due to heart failure.

Action: Clinicians should be aware of this study. Pending additional research it would be wise to use the recently updated the Heart Failure Clinical Guideline produced by the National Institute for Health and Clinical Excellence.

MeReC Extra 46

August 19, 2010 at 1:05 pm | In Prescribing Extra - Drugs |  Print | No Comments

The National Prescribing Centre has published MeReC Extra 46 (PDF) which discusses the place in therapy for simvastatin 80mg daily and the increased risk of cancer observed with angiotensin receptor blockers (ARBs).

The first section notes that earlier this year regulatory authorities drew attention to the increased risk of myopathy with simvastatin at a daily dose of 80mg. This advice is then placed into context with a review of the current Lipid Modification guidance issued by the National Institute for Health and Clinical Excellence (NICE). Statin doses and lipid targets (or the lack of them) are detailed for primary prevention, secondary prevention and acute coronary syndrome (ACS). Clinicians are also reminded that when treatment appears ineffective it is worthwhile checking how concordant the patient is in taking their treatment.

The second section discusses the results of a recent meta-analysis that identified an increased rate of new cancer diagnoses in patients taking ARBs in randomised controlled trials. Although the absolute risk increase is small (1.2% over 4 years) the large number of patients potentially involved means that this information deserves some consideration. Clinicians are advised to review prescribing of ARBs on an individual patient basis. Angiotensin converting enzyme (ACE) inhibitors have more robust efficacy and safety data and may be a suitable alternative.

Action: Clinicians who prescribe statins or ARBs will find this information useful and informative.

Drug Safety Update – August 2010

August 10, 2010 at 9:45 am | In Prescribing Extra - Drugs |  Print | No Comments

The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for August 2010 (PDF).

This issue contains drug safety advice relating to QT and PR prolongation with saquinavir (Invirase^®). Clinicians should be aware of this issue and avoid using saquinavir in patients at high risk of cardiac arrhythmias, and in patients using other drugs that may cause QT and/or PR interval prolongation. In patients already taking saquinavir care should be taken to avoid using other drugs that may cause QT and/or PR interval prolongation.

In the stop press section clinicians are reminded that:

• Modafinil is only recommended for the treatment of narcolepsy. It should not be used to treat excessive sleepiness associated with obstructive sleep apnoea or chronic shift work sleep disorder.
• Rosiglitazone should not be used in patients with a history of heart failure or acute coronary syndrome. It should also be avoided in patients with a history of ischaemic heart disease and only used in combination with insulin under specialist supervision. This reminder is as a result of continued assessment of the drugs safety profile.
• topical ketoprofen is associated with an increased risk of photosensitivity reactions. Patients should be advised to protect their skin from sunlight while using the product and for two weeks after. They should also stop treatment immediately if any skin reaction develops

Action: Clinicians will find this publication to be a useful review of current issues in drug safety.

Calcium supplements link to heart attacks

August 3, 2010 at 3:07 pm | In Prescribing Extra - Drugs |  Print | No Comments

The British Medical Journal has published the results of a meta-analysis that has identified an increased risk of heart attacks in people taking calcium supplements. This analysis has been reported in the general media (BBC).

The analysis identified 15 trials, 5 with patient level data involving 8,151 participants with a median follow up period of 3.6 years and 11 with trial level data involving 11,921 participants with a mean duration of 4.0 years.

The analysis of patient level data found an increased risk of myocardial infarction (Hazard ratio 1.31, 95% CI 1.02 – 1.67, p=0.035) with a similar risk identified in the trial level data (Relative risk 1.27, 95% CI 1.01 – 1.59, p=0.038). There were also non-significant increases in strokes and deaths.

The authors conclude, “Calcium supplements (without co-administered vitamin D) are associated with an increased risk of myocardial infarction” and they urge a review of practice in the management of osteoporosis.

It should be noted that this analysis reviewed calcium supplement against placebo. Vitamin D is known to reduce mortality and as such trials including vitamin D were only included in the analysis if both study groups were treated with vitamin D; this applied to just one study in the 15 analysed.

Using the figures reported in the 11 trial analysis, there were 166 myocardial infarctions among 6,116 participants taking the calcium supplement (absolute risk of 2.71%) versus 130 myocardial infarctions in 5805 participants in the placebo group (absolute risk of 2.24%). This means that if 213 patients are treated with calcium instead of placebo for a period of 4 years 1 patient will be caused to have a heart attack (NNH = 213).

Action: Clinicians should be aware of this study and the media coverage. It would seem prudent to change patients from supplements that only contain calcium to those that also contain vitamin D or to discuss dietary changes to ensure adequate intake of calcium.

Lipitor tablets getting smaller

July 26, 2010 at 1:58 pm | In Prescribing Extra - Drugs |  Print | No Comments

The manufacturer of atorvastatin (Lipitor^®) has written to doctors informing them that smaller round tablets will replace the existing oval shaped tablets across the range of strengths for atorvastatin.

A change in the manufacturing process has allowed the tablets to be made smaller. There will also be some changes to the tablet markings and the product packaging.

Action: Clinicians should be aware of the change and patients can be reassured that the active ingredient is unchanged.

Source: Personal communication