Withdrawal of peripheral vasodilators in primary care

Abstract

Aims

To investigate the use of peripheral vasodilators in selected practices in primary care and to observe the effect of withdrawing therapy in a sample of patients.

Methods

Patients receiving repeat prescriptions for peripheral vasodilators, identified from two practices in Grampian, were interviewed prior to and following withdrawal of therapy.

Results

Of the 35 patients, review of the continued need for therapy was documented in the medical notes of only one patient. Treatment was successfully withdrawn from 17 patients, generating considerable savings.

Conclusions

Review of peripheral vasodilators merits further attention in larger numbers of patients.

Introduction

Peripheral vascular disease occurs as a result of slowly progressing arteriosclerosis, with intermittent claudication, defined as ‘cramping discomfort in the calf clearly provoked by exercise and relieved by some minutes rest’, the commonest symptom [1]. Several agents, including naftidrofuryl and oxpentifylline, are marketed for the treatment of intermittent claudication. Standards for clinical trials of such agents have been proposed [2]. A parallel group, double-blind, placebo controlled design should be employed, with the main method of assessment of response centring on the measurement of pain free and absolute walking distances. Others have proposed guidelines for interpreting results of such trials [3]. Due to the large placebo response often obtained, a difference of less than 40% improvement between drug and placebo may be considered unimportant. Little evidence exists to support the efficacy of peripheral vasodilators according to these criteria.

Given this lack of evidence to support widespread prescribing of these agents, many have recommended restricting use to those patients with disabling symptoms [4–6]. In addition, treatment should initially be for a trial of 2 to 3 months followed by withdrawal to ascertain the need for continued use. The British National Formulary [7] has classified these agents as ‘less suitable for prescribing’ due to limited efficacy. The Audit Commission report of primary care prescribing estimated that restricted use would generate savings amounting to £8.8 million per annum in England and Wales [8].

This work aimed to investigate the use of peripheral vasodilators in selected practices in primary care and to observe the effect of withdrawing therapy in a sample of patients.

Method

The computer systems of two randomly selected general practices in Grampian were used to identify patients receiving repeat prescriptions for peripheral vasodilators. The following information was obtained from these patients' medical notes: age, peripheral vasodilator, dose, duration of therapy, indication, original prescriber and vascular investigations.

A list of patients receiving continuous therapy was circulated to all general practitioners for comment regarding suitability for domiciliary interview. Suitable patients were contacted in writing, explaining patient inclusion criteria and the likely involvement required. These patients were contacted by telephone to seek permission for interview, during which questions focused on knowledge of the peripheral vasodilator, duration of therapy, indication and smoking habits.

Following interview, all patients were contacted in writing and requested to cease therapy for a period of 2 months. Each patient was subsequently contacted by telephone and permission sought to repeat the domiciliary interview to determine the effect of withdrawing therapy.

Statistical analysis was performed using SPSS for Windows Release 6.0.

Results

Forty-five patients (0.4% of the combined lists) were prescribed peripheral vasodilators, 33 (73%) of whom were female and 12 (27%) male, with a median age of 74 years (range 36–88). The fate of these patients in this study is summarised in Figure 1.

Figure 1.

Flow chart indicating fate of patients during study.

Eight patients (18%) had not requested a prescription in the previous year, with the remaining 37 receiving continuous therapy. The most commonly prescribed agent was naftidrofuryl (27 patients) followed by oxerutins (8), inositol nicotinate (2) and oxpentifylline (1). One patient was receiving naftidrofuryl and oxerutins simultaneously.

The majority of patients (26, 70%) were receiving therapy for intermittent claudication. Further indications included varicose veins (3 patients), chilblains (3), gangrenous toes (1), cold hands and feet (1), and leg cramps (1). No indication was documented for four patients (11%). One of these had requested a trial of naftidrofuryl which had then continued without review for 13 years. Therapy had been initiated in primary care in 32 patients (87%), compared with five patients (13%) in secondary care.

The median duration of therapy was 3.5 years (range 0.5–17), with seven patients continuing for greater than 5 years. Review of the continued need for therapy was documented in the medical notes of only one patient (2%), where discontinuation had resulted in symptom recurrence.

The GPs deemed two patients unsuitable for interview due to reasons of old age and receiving chemotherapy. The remaining 35 all agreed to participate in the study. Patients were generally aware of the indication for therapy, citing ‘circulation’ (15 patients) or ‘leg pains’ (8). Two patients claimed therapy to be for ‘blood disorders’ and one for ‘blood clots’. Eleven patients (31%) continued to smoke despite repeated advice to stop.

Patient contact following cessation of therapy excluded one patient due to ill health. Of the remaining 34 patients, six (18%) had continued therapy and a further three refused to participate in the second interview. Complete data were thus available for 25 patients, eight of whom wished to restart therapy due to worsening of symptoms during this period. Treatment was successfully withdrawn from 17 patients (50%), generating annual cost savings of £2768. Duration of peripheral vasodilator therapy was considerably shorter in these patients as illustrated in Table 1.

Table 1.

Comparison of patients successfully stopping therapy with those refusing to stop or wishing to recommence.

Discussion

No previous published work in the UK provided data relating to peripheral vasodilator use in primary care. Naftidrofuryl was the most commonly prescribed agent, being used to treat intermittent claudication in the majority of patients. Further indications identified are outwith manufacturer's recommendations; the use of peripheral vasodilators for these indications is not based on the results of any published work. Despite the lack of evidence to support use in intermittent claudication, several sources [4–6] have acknowledged a limited role in those with disabling symptoms. It is, however, recommended that treatment should be for a period of 2 to 3 months followed by cessation of therapy to ascertain continued need for treatment. This study identified that these agents had been prescribed for considerable periods of time (median 3.5 years) without further review of therapy.

Although therapy was successfully withdrawn from many patients, some perceived a benefit, either refusing to stop therapy or expressing a desire to recommence treatment. These patients had been maintained on therapy for longer periods, reinforcing the need to review and attempt withdrawal at an early stage. This perceived benefit may have been due to a placebo effect as clinical trials have demonstrated increased walking distances in placebo control groups [9].

The results obtained in this study must be interpreted with caution. Cluster sampling was used to identify a relatively small sample of patients. These results are therefore not necessarily generalisable to all patients prescribed peripheral vasodilators in primary care. In addition, a large proportion of patients withdrew from the study at several points. In particular, six patients (18%) had not stopped therapy as instructed and a further three refused to take part in the second interview. Furthermore, this study was not designed as a randomised, double-blind placebo controlled withdrawal of therapy. Such a design would have eliminated many inherent biases, particularly observer bias at interview and would have provided useful information relating to placebo effect. The method used in this study was selected in an attempt to more closely reflect withdrawal of therapy in practice where no placebo agent could be prescribed.

Despite these limitations, this study indicates that regular review and withdrawal of peripheral vasodilators merits further attention in larger patient numbers.