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Volume One Number Two September 1996 |
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ANBP2 Progress Update ANBP2 is now fully functional in all of the five mainland states and also in a number of rural areas. To date almost 8000 patients have been screened with the initial blood pressure check and over 750 patients have been randomised to the Study. The rate of recruitment into the trial has picked up dramatically over the past three months due to the increase in number of nursing staff in the two pilot study states (Victoria and South Australia) and with increasing activity in New South Wales, Queensland and Western Australia.
The Figure shows the rate of subject recruitment to the trail with our target for 1996 aimed at reaching 2000 patients entered. The response from general practitioners to ANBP2 has been overwhelming. To date there are 457 general practitioners registered with the project from around 16 Divisions of General Practice around the country. The majority of these are from Victoria and South Australia, with recruitment only commencing in one or two divisions in the three new states. This response has been greater than our expectations and, I think, underlies the value and level of understanding that general practitioners have in the value of outcome research.
GP Involvement in ANBP2
*Note that NSW, QLD and WA have only recently been recruiting whilst VIC and SA have been involved since the pilot study.
Many of you reading this article will have had study nurses in your practices over the past months and we would be very greatful for your comments and feedback to pass on to other practitioners who may be thinking about participating in ANBP2. It is important that you have your say, so please do not hesitate to send information to us at the National Centre address or use our Toll Free Telephone number 1800 670 695.
Christopher Reid, Director ANBP2.
Facts from the Field - End-Point Monitoring One of the most difficult tasks in ANBP2 is the evaluation of study end-points. The end-point committee (Professors Trefor Morgan, Lindon Wing, Geoff Donnan, and John McNeil) are provided with information gleaned from the review of patient records by the Senior Research Nurses and are blinded as to the treatment group and identity of the patient. Your recording of information will be invaluable in the success of the project in terms of accurately identifying end-points when they occur. Over future issues we will present tips on recording information in your notes that will aid in the objective identification of study end-points.
Congestive Heart (Cardiac) Failure Material required to adequately identify CCF is as follows: 1. Hospital discharge diagnosis of cardiac failure OR 2. Characteristic chest X-ray appearance OR 3. At least 2 of the following 3 definite physical signs - crackles in lung fields - raised jugular venous pressure - ankle oedema In many instances, record reviews have revealed the statement "ankle oedema - ?CCF". If you suspect CCF then for it to be accurately identified at least 2 definite physical signs must be noted in the records. Hard evidence is even better if available eg., Chest X-ray appearance.
Patient Management Tip Remember - after a patient is randomised to a treatment regimen it is important that they stay in the same regimen. Work through the Steps as required to achieve goal blood pressure rather than crossing over. This will result in patient cross-over which will reduce the power of the study.
After Randomisation STEP DOWN - NOT ACROSS
Patient Management Issues Diuretics and Potassium Status There is evidence from case-control studies that the use of non-potassium-sparing diuretics in hypertensives is associated with an increased incidence of sudden death compared with those hypertensives who were receiving potassium-sparing diuretics or other regimens which did not include non-potassium-sparing diuretics (1,2). This association was probably more likely in subjects who already had evidence of cardiac disease or were at greater risk of having cardiac disease. The implication of this finding for patients who have been randomised to the 'diuretic' arm of ANBP2 is that you should be aware of your patients potassium status and take appropriate action if it is abnormal.
Low dose diuretics We wish to remind you that for subjects who are randomised to the DIURETIC arm of ANBP2 we are recommending commencing treatment with a 'low' dose of a thiazide or thiazide-like agent. This should help to minimise the adverse biochemical effects of the diuretic. What do we mean by a 'low' dose of a diuretic? In general 'low' doses of the thiazides or related agents used in the management of hypertension are half the usual recommended daily dose, although for some agents, e.g., indapamide, the usual daily dose is equivalent in potency terms to half that of the noire established agents particularly in relation to the biochemical effects. Our recommended starting daily doses for the available thiazide diuretics and related agents are: bendrofluazide (Aprinox) 2.5mg = 1/2 *5mg tablet chlorthalidone (Hygroton) 12.5mg = 1/2 *25mg tablet chlorothiazide (Chlotride) 250mg = 1/2 *500mg tablet hydrochlorothiazide (Dichlotride) 25mg = 1 *25mg or 1/2 *50mg tablet indapamide (Natrilix, Dapatabs) 2.5mg = 1 *2.5mg tablet methyclothiazide (Enduron) 2.5mg = 1 *2.5mg or 1/2 *5mg tablet metolazone (Diulo) 1.25mg = 1.2 *5mg tablet What about combination with a potassium-sparing agent? We are not currently recommending that you start with a combination agent which incorporates both a thiazide and a potassium-sparing agent. Rather we are suggesting that you monitor plasma potassium concentration at 1 month after starting treatment and institute an appropriate measure for those subjects in whom the plasma potassium concentration is below the reference range. One strategy in this situation would be to add a potassium-sparing agent and an alternative would be substitution of a combination agent. A more cumbersome alternative is to administer potassium supplement. So that you can continue the 'low' dose of the thiazide agent with a potassium-sparing drug, we would recommend: EITHER addition of amiloride 2.5 mg daily = 1/2 *5mg tablet (Kaluril) OR substitution with: hydrochlorothiazide 25mg plus amiloride 2.5mg daily = 1/2 *Amizide tablet or hydrochlorothiazide 25mg plus triamterene 50mg daily = 1 *Dyazide or Hydrene tablet
Monitoring Plasma Biochemistry For all subjects randomised into ANBP2, either in the diuretic or ACE inhibitor arm, it is wise to measure plasma electrolytes, urea and creatinine concentration about one month after starting therapy, and for subjects in the DIURETIC ARM also measure plasma urate and glucose. If an abnormality is detected, an appropriate strategy may need to be introduced with further biochemical monitoring at least at monthly intervals until a satisfactory situation has been produced. Once a stable and acceptable biochemical profile has been demonstrated, we would recommend checking plasma biochemistry at least annually.
Diuretic Arm For subjects randomised to the diuretic arm of the study, the possible biochemical abnormalities are: hyponatraemia hypokalaemia hypochloraemia alkalosis (usually with hypochloraemia) raised plasma urea and/or creatinine hyperuricaemia hypomagnesaemia hypercalcaemia
Hypnotraemia: The common problems requiring attention are: Usually present with some or all of the other biochemical abnormalities and indicates an excess loss of salt and water with continuing water intake. Recommended strategies are: EITHER Reduce diuretic dose, e.g., halve current dose (this may require giving the drug only on alternate days) and advise against excessive water intake. OR Cease diuretic and change to a drug from one of the classes in STEP 2 of the DIURETIC ARM
Hypokalaemia: Often present with some or all of the other biochemical abnormalities especially hypochloraemia alkalosis. Recommended strategies are: EITHER addition of amiloride 2.5mg daily = 1/2 *5mg tablet (Kaluril) OR substitution with: hydrochlorothiazide 25mg plus triamterene 50g daily = 1 *Dyazide or Hydrene tablet
Hypochloraemic alkalosis: This abnormality alone is usually not treated but does indicate that a biochemical effect of the diuretic is present. Usually partially corrected when either hyponatraemia and/or hypokalaemia is treated.
Raised plasma urea and/or creatinine: A raised plasma urea either with or without an increase in plasma creatinine usually indicates greater than expected volume depletion associated with the diuretic therapy. Recommended strategies are similar to those when hyponatraemia is present namely: EITHER Reduce diuretic dose, e.g., halve current dose (this may require giving the drug only on alternate days) and advise against excessive water intake. OR Cease diuretic and change to a drug from one of the classes in STEP 2 of the DIURETIC ARM.
Hyperuricaemia: There is always an increase in the plasma uric acid concentration when a thiazide diuretic is being taken, the magnitude of the increase being dependent on the diuretic dose. The clinical significance of the increase depends on the magnitude of the uric acid concentration and whether or not clinical gout has occurred. Recommended strategies are: If plasma uric acid > 0.60 mmol/l and/or the subject has not suffered from gout, ensure that the subject is on a low dose of diuretic and monitor plasma urate intermittently, e.g., every 6 months to ensure that it is not increasing. If plasma urate is 0.60mmol/l and/or the subject has suffered from gout: EITHER cease the diuretic and substitute with a drug from one of the classes in STEP 2 of the DIURETIC ARM. OR continue diuretic at same or current dose and add allopurinol in a daily dose sufficient to reduce plasma urate into the laboratory reference range preferably <0.40 mmol/l.
Hyperglycaemia: Thiazide diuretics and related agents may interfere with glucose tolerance and thus result in new clinical diabetes or in the worsening of glycaemic control with existing diabetes. Whether this effect will occur in a particular subject cannot be predicted. Recommended strategies are: EITHER cease the diuretic and substitute a drug from one of the classes in STEP 2 of the DIURETIC ARM OR continue the diuretic at half the current dose initially and observe whether glycaemic control improves to a satisfactory level; if so continue that dose of the diuretic. If glycaemic control does not improve with diuretic dose reduction, either cease the diuretic and substitute a drug from one of the classes in STEP 2 of the DIURETIC ARM or increase the current diabetic treatment regimen.
Who's Who in ANBP2 Dr David Gleave (top left), Regional Director, Western Australian Regional Centre. I graduated from Leeds University in 1982 and completed GP vocational training in the UK. I moved to Australia in 1988 - the year I married Gillian, who is a Canadian nurse. My first work in Australia was as a general practitioner in rural Queensland. We moved to Western Australia in 1989. I have spent most of the past five years employed as a GP by an Aboriginal health service in Carnarvon in the North-West of Western Australia. My interest in GP based research was stimulated by our attempts to test the effect of our activities in Carnarvon. It received a boost in 1995 when I enrolled in the Graduate Diploma in Family Medicine as an external student at Monash University and so was able to study research methods. I have an interest in medical education and have had the pleasure of being trainer to several superb trainees through the RACGP training program over the past five years. Currently I do sessional work as an External Clinical Tutor with the Perth-based RACGP training program. I consult part-time in a practice in Perth's northern suburbs. We have two children with a third expected any day now!
Marja Cehun (bottom right), Regional Nurse Victorian Regional Centre How often have we heard that? Well, over the part three decades, I was fortunate enough to fulfil my dreams and develop my nursing skills into a satisfying and interesting career. The nuns at St. Vincent's Hospital Melbourne ensured I had a thorough and disciplined training in general nursing. Romance and marriage overseas took care of the wanderlust, and the birth of three children gave me a very good grounding in midwifery and mothercraft. Accounting, budgeting, management and organisational skills became fine tuned through running a household and the successful development of time management and teamwork within our family unit enabled us to make the most of our time together at home and living and travelling overseas. Community health and education have been my main interests in nursing and the experience that I have gained over the past fifteen years in this field have culminated in my involvement with the ANBP2 team as one of the research nurses.
EDITOR'S NOTE: Congratulations to David and Gillian Gleave on the arrival of Annie Sarah born June 10, 1996
National Launch July 20, 1996 ANBP2's National Launch took place on Saturday, July 20, 1996 with an audience of over 300 general practitioners. The official launch was conducted by Dr David Graham, Head of the Pharmaceutical Benefits Scheme, who reinforced the role the Commonwealth Government is playing in the conduct of ANBP2. Dr Graham's opening focused on the need for outcome-based assessment of benefit of different types of therapies, particularly those which have a high impact on the public purse.
Dr Graham said that the government realised there would possibly be extra visits and expenses associated with the conduct of ANBP2, but the outcome of this type of study has a great potential to influence the direction that governments take and provide a sound basis and rationale for continued support of medication subsides. Professor Lindon Wing also spoke on the underlying principles of ANBP2 and how its implementation into normal function in general practice can be facilitated. The launch was conducted at the University of Sydney in association with the Merck Sharp & Dohme Continuing Education University Program Weekend. The launch also coincided with the establishment of the New South Wales Regional Centre and the commencement of activities in all five mainland states. ANBP2 Contacts |
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