☀️     🌓

Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog


In 2000, the HOPE Study1 was published in the New England Journal of Medicine.

This study has been followed up for a further two and a half years with about two thirds of the original trial population in the HOPE - The Ongoing Outcomes Study2 (or Hope-TOO). During this open label follow up, patients were assessed for the same outcomes as the original HOPE Study, but of course the placebo arm patients were no longer denied ramipril therapy.

Around 70% of patients in both arms of the study were taking an ACE Inhibitor over the course of the study extension, with over 90% of taking ramipril. The overall effect was that the event rates in the two arms paralleled each other as the effects of the drug in the placebo arm now matched the effects in the active arm.

This study doesn't really add any further evidence but it does increase our confidence that the benefits of ramipril seen under trial conditions can be extended into a more open environment, such as primary care.

Action: ACE Inhibitor use is recommended in patients with hypertension and those who are at high cardiovascular risk. They are also of benefit in protecting renal function in patients with diabetes. Ramipril is a first line ACE Inhibitor.


  1. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med 2000;342:145-53.
  2. Long-term effects of ramipril on cardiovascular events and on diabetes. HOPE/HOPE-TOO Study Investigators. Circulation 2005;112:1339-1346.

Share 'HOPE-TOO' on Email Share 'HOPE-TOO' on Delicious Share 'HOPE-TOO' on Digg Share 'HOPE-TOO' on Facebook Share 'HOPE-TOO' on reddit Share 'HOPE-TOO' on Twitter


The Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA) was made available early via the Lancet website late last week. The media have already picked up on this new study with the BBC and newspapers like the Telegraph reporting the headline findings of the trial.

Action: The outcomes of the study could be entirely driven by greater reductions in blood pressure that occurred in the Amlodipine arm. Until NICE release their new Guideline prescribers should continue to use the current NICE Hypertension Guideline. For more detail, read on.


Detail: This study was started about 6 years ago and compared the blood pressure lowering effects of Atenolol with Bendroflumethiazide to those of Amlodipine with Perindopril. The Primary Outcome of the trial was Non fatal MI (including silent MI) and fatal CHD. There was no statistical difference between the two arms of the study in this endpoint.

Where there was a statistical difference in the secondary outcomes, perhaps it would have been expected. For example there was less peripheral arterial disease and development of diabetes in the Amlodipine and Perindopril arm. This is to be expected due to the peripheral vasodilation effects of Amlodipine and Perindopril compared to Atenolol and Bendroflumethiazide. And we already know about the diabetes risk posed by the combination of Beta-blockers and Diuretics.

Some purists may be critical of the trial on two points, firstly that the Atenolol comparator arm is not reflective of current practice (the dose of Atenolol could be titrated to 100mg) and the fact that a post-hoc analysis was conducted that shows benefit for the Amlodipine arm (but this analysis was not defined at the start of the study). If these limitations in the study are accepted does it add anything new to the body of evidence in Hypertension?

At the same time the paper was released by the Lancet, they released another paper investigating the role of blood pressure and other variables in the results. This was perhaps seen as necessary because there was a difference in the blood pressures of the two arms of 2.7/1.9mmHg in favour of the Amlodipine arm. There were also favourable differences, towards the Amlodipine arm, for BMI, Triglyceride, creatinine, blood glucose and HDL.

Overall, this investigation found that correcting for these variables reduced the differences by about half for coronary events and by just under half for stroke events, and that neither were statistically significant after the correction.

NICE have released a statement detailing a collaborative project with the British Hypertension Society to review the BHS and NICE Hypertension guidelines following publication of this study. This process is likely to take six months.

Action: A detailed appraisal of the study reveals that it doesn't really add a great deal to our current knowledge. The outcomes of the study could be entirely driven by greater reductions in blood pressure that occurred in the Amlodipine arm. Until NICE release their new Guideline prescribers should continue to use the current NICE Hypertension Guideline.


  1. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a mulitcentre randomised controlled study. ASCOT Investigators Lancet 2005;366:895-906.
  2. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). ASCOT Investigators Lancet 2005;366:907-903.

Share 'ASCOT - BPLA' on Email Share 'ASCOT - BPLA' on Delicious Share 'ASCOT - BPLA' on Digg Share 'ASCOT - BPLA' on Facebook Share 'ASCOT - BPLA' on reddit Share 'ASCOT - BPLA' on Twitter


Fosavance has been launched by MSD. This product contains Alendronate 70mg and colecalciferol 70micrograms in a once a week tablet. It will be priced at the same level as Fosamax, that is an NHS List price of £22.80 for 4 tablets.

It is licensed for the treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency. Further information is available in the Summary of Product Characteristics.

At present, Bisphosphonates (like Alendronate) are recommended for use in addition to a suitable Calcium and Vitamin D supplement. This product is being promoted based upon the fact that population data in the UK shows that the vast majority of people obtain sufficient calcium from their diet. The exception to this appears to be female patients who are aged over 65 and who live alone.

This product is an attempt at patent extension by the manufacturers of Fosamax as the patent is due to expire very soon. The place for this product remains unclear at present as supplementation with Calcium and Vitamin D supplements is the current empirical treatment.

Additionally, it may be difficult to assess the risk of Vitamin D insufficiency in order to comply with the product license. The skin produces Vitamin D naturally during exposure to sunlight.

Action: This product should not be used in preference to standard treatment (Calcium and Vitamin D supplement with or without a Bisphosphonate) until further data can demonstrate that Calcium supplementation is not required in patients who have already suffered an osteoporotic bone fracture, especially as patients with "postmenopausal osteoporosis" are likely to be female patients who are over 65 and living alone.

Share 'Fosavance' on Email Share 'Fosavance' on Delicious Share 'Fosavance' on Digg Share 'Fosavance' on Facebook Share 'Fosavance' on reddit Share 'Fosavance' on Twitter

QOF Data Available Online

The Department of Health have released a breakdown of the QOF data that has been collected in the last financial year as part of the GP contract.

The data available so far gives information on the prevalence of the diseases covered by the GMS Clinical Domains and also a breakdown of the points achieved by each Primary Care Trust.

Ideally, these two reports should be viewed together as points achievement may be associated with prevalence - the more people there are in a locality with a disease the harder it may be to attain maximum points.

The two reports are available in Adobe Acrobat format, to read them download the free Acrobat Reader.

Share 'QOF Data Available Online' on Email Share 'QOF Data Available Online' on Delicious Share 'QOF Data Available Online' on Digg Share 'QOF Data Available Online' on Facebook Share 'QOF Data Available Online' on reddit Share 'QOF Data Available Online' on Twitter

Type II Diabetes

Diabetes is a relatively common and very serious disease. The treatment of diabetes tends to focus upon the diagnostic measures for the disease, those of blood sugar assessment. Despite this the United Kingdom Prospective Diabetes Study1 (UKPDS) has shown the tight blood sugar control should be a secondary target to tight blood pressure control.

Tight blood pressure control was found to contribute to reductions in deaths from long term complications, strokes and serious deterioration in vision. Tight blood glucose control contributes to a reduction in eye disease and renal damage. It is clear from this that the focus should be upon saving lives not purely preserving renal function and vision.

Another key finding of UKPDS was that in addition to the glucose benefits of Metformin there are additional reductions in the risk of myocardial infarction in comparison to other anti-diabetic agents. Metformin should therefore be the first line anti-diabetic drug in all patients with Type II Diabetes.

NICE appraised the place of the Glitazones in August 2003. This appraisal recommended the use of Glitazones when patients cannot tolerate or are contraindicated to either Metformin or Sulphonyureas. Since this appraisal the evidence supporting the use of Glitazones has grown beyond demonstrated effects in lowering blood sugar. Given that Sulphonylureas tend to cause weight gain as they cause insulin secretion and therefore stimulate appetite, perhaps a more pragmatic approach should now be used when HbA1c remains sub-optimal.

  1. Metformin for all patients, titrate to maximum tolerated dose
  2. If BMI < 25 Kg/M2 use a Sulphonylurea (Glicalazide or Glipizide)
  3. If BMI > 25 Kg/M2 use a Glitazone (Pioglitazone or Rosiglitazone)
  4. Refer for, or initiate Insulin (Triple therapy is licensed but not recommended for Primary Care. The combination carries extra risks for Heart Failure and Hypoglycaemia and therefore requires close monitoring

Action: Prescribers should aim to control blood pressure in preference to blood glucose in patients with Type II Diabetes.

Treatment of blood glucose should be initially managed with Metformin in all patients with type II Diabetes.


  1. United Kingdom Prospective Diabetes Study

Share 'Type II Diabetes' on Email Share 'Type II Diabetes' on Delicious Share 'Type II Diabetes' on Digg Share 'Type II Diabetes' on Facebook Share 'Type II Diabetes' on reddit Share 'Type II Diabetes' on Twitter

Newer Posts »

Prescribing Advice for GPs is powered by ClassicPress.
Subscribe for Free to our RSS or Atom Feeds for New Entries.