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Pharmacological prevention of cardiac risk in claudicants with ischaemic heart disease

F. Torella S. Washington A. Cooper A.D. Parry C.N. McCollum
Academic Surgery Unit, South Manchester University Hospital, Manchester, U.K.
Correspondence to: F. Torella, 5 Hall Lane, Kelsall, Nr Tarporley, Cheshire, CW6 0QY Email: FCMTDR@aol.com

Introduction

Keywords: Ischaemic heart disease, peripheral vascular disease, secondary prevention
Surg J R Coll Surg Edinb Irel., 1 October 2003, 296-298

Background: Claudicants rarely progress to critical limb ischaemia but have a threefold increase in mortality, mainly due to cardiac disease. Antithrombotic therapy, beta blockers, ACE inhibitors and statins have been shown to reduce mortality and cardiovascular morbidity in patients with ischaemic heart disease. Aim: To investigate secondary pharmacological prevention of ischaemic heart disease in claudicants. Materials and Methods: We prospectively recorded comorbidity and drug treatment in 89 patients (67 men and 22 women) with a history of ischaemic heart disease recruited in a supervised exercise and lifestyle modification programme to improve claudication distance and prognosis. Results: Of the 89 cases, 40 had a history of angina only and 49 of myocardial infarction. Sixteen (18%) had diabetes, 47 (53%) had hypercholesterolaemia and 52 (58%) were hypertensive. Antithrombotic therapy was prescribed to 61 patients (68.5%), 64 (72%) with a history of myocardial infarction and 27 (67.5%) with angina only (p = 1). Beta-blockers were prescribed to 12 (13.5%) patients only, seven (15%) with a history of myocardial infarction and five (12.5%) with angina only (p = 1). Of the 47 patients with hypercholesterolaemia, 29 (62%) were on a statin. Conclusion: Secondary pharmacological prevention of ischaemic heart disease in claudicants remains suboptimal, with only two thirds of patients receiving antithrombotic therapy and a small minority receiving beta blockers. Pharmacological prevention in claudicants should improve to reduce cardiac morbidity and mortality

INTRODUCTION
Intermittent claudication is a common symptom of diffuse atherosclerosis. Its prevalence increases with age, affecting up to 25% of the population over the age of 85 years.¹ The prognosis of limb in claudicants is good, with only a minority progressing to critical ischaemia and amputation. Peripheral vascular disease, however, is a marker of generalised atherosclerosis, resulting in high mortality rates secondary to myocardial infarction and stroke.^2-3

Lifestyle modifications, including smoking cessation, weight control and exercise, are widely advocated to reduce cardiovascular morbidity and mortality. Furthermore, a number of pharmacological interventions have been shown to prolong life or decrease the incidence of cardiac events in patients with overt ischaemic heart disease and should be offered to claudicants with a history of angina or myocardial infarction.

Antithrombotic therapy with antiplatelet agents is a mainstay of pharmacological risk prevention, which should be offered to all claudicants unless contraindicated.4 Beta adrenergic receptors blockers have clearly been shown to prolong life after myocardial infarction or a diagnosis of cardiac failure. According to the National Institute for Clinical Excellence, appropriate therapy should be offered to all patients with these conditions.^5-9

Even in cases of mild angina, beta blockade reduces the number of ischaemic episodes during daily activity.¹⁰ Claudicants with hypercholesterolaemia should also be offered treatment with statins, which have also been shown to reduce the incidence of cardiac events after myocardial infarction.¹¹ The aim of this study was to investigate current pharmacological prevention practice in claudicants with a clinical diagnosis of ischaemic heart disease in Britain.

METHODS
We reviewed prospectively collected databases including 525 claudicants recruited in a lifestyle modification and supervised exercise programme from May 1997 to June 2001. The programme was run by a specialist nurse in our tertiary vascular unit serving a large population in the North West of England. Eighty-nine patients (17%) with a clinical diagnosis of ischaemic heart disease were identified. Demographics, cardiovascular comorbidity and drug treatment on the day of recruitment into the programme, were recorded.

Continuous variables were presented with means and standard deviations (SDs). Categorical data were presented with proportions, percentages and 95% confidence intervals (CIs), and compared with either the chi squared test (with a continuity correction) or the Fisher’s exact test.

RESULTS

Demographics and comorbidity
Of the 89 cases studied, 67 (77%) were men and 20 (23%) women. Forty (46%) had a history of angina only and 49 (54%) of myocardial infarction. Of the 49 with a history of myocardial infarction, 29 (59%) also had angina. The mean age (SD) was 68 (9) years: 67 (10) years in those with angina only 68 (7) years in those with a history of myocardial infarction. Sixteen (18%) had diabetes, 47 (53%) had hypercholesterolaemia and 52 (58%) were hypertensive.

Pharmacological treatment
Antithrombotic therapy (antiplatelet agents or warfarin) was prescribed to 61 patients (68.5%; 95%CI = 58-77%): 27 (67.5%) with angina only and 34 (72%) with a history of myocardial infarction (p = 1). Beta blockers were prescribed to 12 (13.5%; 95%CI = 8-22%) patients only: five (12.5%) with angina only and seven (15%) with a history of myocardial infarction (p = 1). Of the 47 patients with hypercholesterolaemia (random cholesterol equal to or greater than 5.5 mmol/L), only 29 (62%; 95%CI = 47-74%) were on a statin: 12/20 (60%) of those with angina only and 17/27 (63%) of those with a history of myocardial infarction (p = 1). Additional cardiac medications included calcium channel blockers in 29 patients (33%: 95%CI = 28-48%), ACE inhibitors in 26 (29%; 95%CI = 24-43%) and ‘other’ (usually nitrates or antiarrhythmic agents) in 39 (44%; 95%CI = 34-54%), with similar use by patients with angina or a history of myocardial infarction.

DISCUSSION
Of our 89 claudicants with ischaemic heart disease, only two thirds were on antithromboitc therapy and a small minority was on beta blockers. Furthermore, only two thirds of patients with raised cholesterol were on statins. There were no differences in pharmacological treatment between claudicants with angina only and those with a history of myocardial infarction.

To our knowledge, this is the first report on pharmacological preventive practice in UK claudicants with ischaemic heart disease. Our results are remarkably similar to those of a recent study from Canada, showing a poor preventive practices in patients admitted to hospital for peripheral vascular surgery, and indicate suboptimal treatment.¹²

There is little argument against the need for appropriate antithrombotic therapy in these patients. The Heart Protection Study demonstrated that statins reduce mortality by one third in patients with peripheral vascular disease regardless of cholesterolaemia, but our patients were recruited before the publication of this evidence.¹³ Few clinicians, however, would argue against the use of cholesterol lowering drugs in those with a random cholesterol concentration equal to or greater than 5.5mmol/L, with current guidelines recommending a statin after acute myocardial infarction.⁹

Peripheral vascular disease has often been cited as a relative contra-indication to beta blockade which, in some cases, could decrease blood flow to the limbs to a critical level. This concern is based on occasional reports of adverse events or small studies demonstrating a decrease in perfusion to peripheral tissues.^14-18 Other authors have failed to demonstrate a reduction in blood flow or worsening of symptoms by beta blockers. A recent review concluded that beta blockade is not necessarily contraindicated, in the presence of peripheral vascular disease.^19,20,21 New cardioselective beta blockers with additional vasodilator properties are now available.^22-24 These products could constitute a viable alternative to traditional agents with a potential beneficial effect on symptoms of peripheral vascular disease. Even in the presence of mild side effects, however, beta blockers may still be indicated in claudicants with ischaemic heart disease due to the overwhelming evidence on their efficacy in preventing cardiac adverse events.^5-10 Further benefits of beta blockers include a reduction of peri-operative myocardial ischaemia and cardiac complications in high-risk patients undergoing peripheral vascular surgery, and an increase in medium-term survival for moderate risk patients undergoing any major surgery.^25-27 In addition to beta blockers and antithrombotic therapy, ACE inhibitors are also recommended after myocardial infarction but less than half of our patients were on these drugs.⁹

In conclusion, this study showed that preventive practices in the UK need to be improved to reduce cardiac mortality among claudicants with ischaemic heart disease. In view of the high prevalence of asymptomatic coronary atherosclerosis in these patients, it would also be appropriate to investigate the effect of additional pharmacological treatments, such as beta blockade, on cardiac risk in claudicants without overt ischaemic heart disease. This evaluation should be conducted by adequately powered randomised trials, with accurate recording of compliance, side effects, walking distances and quality of life.

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