Evidence for an age and gender bias in the secondary prevention of ischaemic heart disease in primary care

Abstract

Aims

To determine if a gender or age bias exists in the prescription of important secondary preventive therapies for ischaemic heart disease in primary care.

Methods

We identified 15 590 patients with ischaemic heart disease on the basis that they received a prescription for nitrate therapy over a 1-year period (September 1999 to August 2000) from the Eastern Region of the General Medical Services scheme in Ireland (population of 334 031), which provides free health service to those eligible patients in primary care. Odds ratios (OR) for the prescription of aspirin, β-blockers, statins, calcium channel antagonists and ACE inhibitors in women and in those aged> 65 years were determined.

Results

Female patients were less likely to receive a prescription for a β-blocker [OR = 0.84, 95% confidence interval (CI) = 0.79, 0.89, P < 0.001], aspirin (OR = 0.72, 95% CI = 0.67, 0.78, P < 0.001), and ACE inhibitors (OR = 0.83, 95% CI = 0.78, 0.89, P < 0.001) compared with their male counterparts. However, women were more likely to receive anxiolytic benzodiazepines (OR = 1.71, 95% CI = 1.59, 1.85, P < 0.001) compared with their male counterparts. Elderly patients (aged> 65 years) were less likely to receive aspirin (OR = 0.92, 95% CI = 0.85, 0.99, P < 0.001), β-blocker (OR = 0.66, 95% CI = 0.62, 0.71, P < 0.001) and a statin (OR = 0.5, 95% CI = 0.46, 0.53, P < 0.001).

Conclusions

An age and gender bias exists in the prescription of important secondary preventive therapies in primary care that may lead to increased mortality from ischaemic heart disease in these groups.

Introduction

The Cardiovascular Health Strategy Group was established in 1998 in Ireland to develop a strategic approach to reduce avoidable death and illness caused by cardiovascular disease [1]. It set out the blueprint for treating heart disease in Ireland, which has the third and sixth highest mortality rates world-wide for ischaemic heart disease for men and women, respectively [2]. Furthermore, the decline in ischaemic heart disease in Ireland has been slower in women compared with men [3]. The prescribing of aspirin [4], β-blockers [5], statins [6] and more recently ACE inhibitors [7] has been shown to be effective in the secondary prevention of coronary artery disease whilst the evidence regarding the benefits of calcium channel antagonists is equivocal [5]. However, there is evidence to suggest that a gender [8] and age [9] bias exists in the management of coronary heart disease. Little information is available regarding the existence of this bias in primary care, where the majority of patients with coronary heart disease are cared for. Nitrate prescribing has been shown to be a useful surrogate marker for coronary heart disease with a sensitivity (i.e. the percentage of patients with ischaemic heart disease who are prescribed nitrates) of approximately 73% and specificity (% of patients identified by nitrate therapy who actually have ischaemic heart disease) of 96% [10].

We wished to determine the adherence to established guidelines for the secondary prevention of ischaemic heart disease, and whether there exists a gender or age bias in the prescription of secondary preventive therapies in primary care.

Methods

The General Medical Services (GMS) scheme provides free health service to approximately 31% of the Irish population and has been described in detail elsewhere [11]. Eligibility for free health care is means-tested, and is confined to those who are unable without undue hardship to arrange general practitioner services for themselves and their dependants. All medicines are dispensed to such patients without charge. While the GMS population (1.24 million), comprising just over a third of the Irish population, cannot be regarded as representative of the general population, as socially disadvantaged persons, children and the elderly are over-represented, they nevertheless receive some 70% of all medicines prescribed in Irish general practice. Prescriptions are dispensed through community pharmacies operating within the scheme and a computer system is used for processing pharmacists’ claims, which in addition to providing details on prescription claims also contains, unlike Prescription Analysis and Cost (PACT) data, demographic data on patients such as age and sex. No information on diagnosis is recorded. All prescription items are coded according to the WHO Anatomical Therapeutic Chemical (ATC) classification system [12].

Ireland is divided into eight regions for the administration of health services. We examined the prescription database of the GMS from the largest region, the Eastern Regional Health Authority (population of 334 031 or 28% of the total GMS, which includes the counties of Dublin, Wicklow and Kildare) over a 12-month period (September 1999 to August 2000) and identified those patients who received a prescription for a nitrate (ATC code C01DA). We then examined the number of nitrate patients who received a prescription for a β-blocker, calcium channel antagonist, statin, aspirin, or ACE inhibitor over the study period. Logistic regression analysis was used to determine the odds ratios (ORs) for these medications for females compared with males. The ORs were adjusted for the effect of age. As depression and anxiety are associated with ischaemic heart disease [13, 14] and for comparison purposes we also determined ORs for noncardiovascular drugs including antidepressants, anxiolytic benzodiazepines (as defined in the British National Formulary [15]), nonsteroidal anti-inflammatory drugs, insulin and antiepileptic medications in this group of patients. One would not expect a gender difference in the prescription of medications such as insulin or antiepileptic medications where prescribing is not discretionary. A similar analysis was performed for elderly patients (i.e. those aged> 65 years). A control population (i.e. those who did not receive cardiovascular drugs over the study period and aged> 16 years) consisting of 191 311 (M : F 73 386 : 117 925, mean age M : F 44.7 ± 18.3 : 42.9 ± 18.9 years) was identified to compare the prescribing of such therapies.

Results

We identified a total of 15 590 patients (M : F 7751 : 7839, mean age M : F 65.5 ± 10.8 : 67.7 ± 10.9 years) who received at least one prescription for a nitrate preparation over this period of time. A total of 113 770 prescriptions were dispensed for nitrates, of which the majority were for isosorbide mononitrate (56.2%) followed by glyceryl trinitrate (38.5%) and isosorbide dinitrate (5.3%). The 1-year prevalence of nitrate prescribing rose from 11.6% (M : F 15.1 : 9.6%) in those aged> 55 years, to 12.3% (M : F 16.1 : 10.3%) in those aged> 65 years.

The number (and percentages) of patients who received a prescription for a β-blocker, calcium channel antagonist, statin, aspirin or ACE inhibitor are shown in Table 1. Using the χ² statistic, the gender difference was statistically significant (P < 0.001) for all of these medications. These differences were unaltered if one selected patients receiving a single nitrate prescription or those receiving chronic nitrate therapy (i.e.> 2 months nitrate therapy) over the study period for the analysis. ORs and 95% confidence intervals (CIs) for women receiving these medications were determined and are shown in Table 2. Women with ischaemic heart disease were less likely to receive a prescription for aspirin, calcium channel antagonists, β-blockers or ACE inhibitors, whilst there was no statistical difference in the prescription of statins when adjusted for age. The results of a similar analysis for noncardiovascular drugs are shown in Tables 3 and 4. Women receiving nitrates had higher odds of receiving an anxiolytic benzodiazepine (OR = 1.71, 95% CI = 1.59, 1.85), which was also to a much greater extent than in women in the control population (OR = 1.2, 95% CI = 1.16, 1.23, test for interaction, gender by cardiovascular disease, P < 0.001). In contrast, there was little difference in the prescription of antidepressants in women receiving nitrates (OR = 1.55, 95% CI = 1.43, 1.69, P < 0.001) when compared with the control population (OR = 1.46, 95% CI = 1.41, 1.50, P < 0.001). No gender difference was noted among patients prescribed nitrates in the prescription of therapy that is nondiscretionary, such as insulin or antiepileptic therapy (Tables 3 and 4).

Table 1.

Number (%) of nitrate patients who received a prescription for a β-blocker, calcium channel antagonist, statin, aspirin, or ACE inhibitor

	β-blocker (%)	Calcium channel antagonist (%)	Statin (%)	Aspirin (%)	ACE inhibitor (%)
All	6243 (40)	6034 (38.7)	4699 (30.1)	11425 (73.3)	5131 (32.9)
Male	3346 (43.2)	3112 (40)	2490 (32.1)	5952 (76.8)	2674 (34.5)
Female	2847 (37)*	2924 (37.3)*	2209 (28.2)*	5473 (69.8)*	2457 (31.3)*

^*Statistically different from male, P < 0.001).

Table 2.

Unadjusted and adjusted (for age) Odds ratios and 95% confidence intervals (CIs) for the prescription of β-blockers, calcium channel antagonists, statins, aspirin, warfarin and ACE inhibitors in women who received a prescription for nitrate therapy

Drug	Odds ratio (95% CI)	Adjusted Odds ratio (95% CI)
β-Blocker	0.77* (0.72, 0.82)	0.84* (0.79, 0.89)
Calcium channel antagonist	0.89* (0.83, 0.95)	0.89* (0.83, 0.95)
Statin	0.83* (0.77, 0.89)	0.97 (0.91, 1.05)
Aspirin	0.7* (0.65, 0.75)	0.72* (0.67, 0.78)
ACE inhibitor	0.87* (0.81, 0.93)	0.83* (0.78, 0.89)

^*P < 0.001.

Table 3.

Number (%) of nitrate patients who received a prescription for an antidepressant, benzodiazepine, insulin, antiepileptic, antiulcer drugs or NSAID

	Antidepressants	Benzodiazepines	NSAIDs	Anti-epileptics	Insulin
All	2858 (18.3)	3578 (22.4)	6199 (39.8)	649 (4.2)	317 (2)
Male	1179 (15.1)	1447 (18.6)	2889 (37.3)	321 (4.1)	157 (2)
Female	1679 (21.4)*	2131 (27.1)*	3310 (42.2)*	328 (4.2)	160 (2)

^*P < 0.001.

Table 4.

Unadjusted and adjusted (for age) Odds ratios (ORs) and 95% confidence intervals (CIs) for the prescription of antidepressants, benzodiazepines, insulin, antiepileptics, antiulcer drugs and NSAIDs in women who received a prescription for nitrate therapy

Drug	Unadjusted OR (95% CI)	Adjusted Odds ratio (95% CI)
Antidepressants	1.51* (1.4, 1.65)	1.55* (1.43, 1.69)
Benzodiazepines	1.63* (1.51, 1.75)	1.71* (1.59, 1.85)
NSAIDs	1.23* (1.15, 1.31)	1.26* (1.2, 1.34)
Antiepileptics	1.0 (0.86, 1.18)	1.1 (0.9, 1.24)
Insulin	1.0 (0.81, 1.26)	1.1 (0.88, 1.34)

^*P < 0.001.

In a separate analysis we found that the elderly who were prescribed nitrate therapy were less likely to be prescribed a β-blocker (OR = 0.66, 95% CI = 0.62, 0.71), statin (OR = 0.5, 95% CI = 0.46, 0.53) or aspirin (OR = 0.92, 95% CI = 0.85, 0.99) and were more likely to receive a prescription for a calcium channel antagonist (OR = 1.14, 95% CI = 1.1, 1.20) and ACE inhibitor (OR = 1.51, 95% CI = 1.41, 1.63).

Discussion

Our results suggest that there is a gender and age bias in the prescription of secondary preventive therapies. Differential prescribing patterns for women compared with men have been described for a number of diseases [16, 17]. Whilst coronary artery disease is the leading cause of death in women, with a mortality rate exceeding that for all neoplastic diseases combined [8], women do not usually list heart disease among the health problems they consider important [18]. The investigation and management of cardiovascular disease is different in women compared with men [19, 20]. Women are less likely to receive secondary prophylaxis with β-blockers or aspirin following a myocardial infarct [21] and have a higher risk of reinfarction [22] and unstable angina [23] following a myocardial infarct.

Research performed in primary care has shown that doctors’ interpretations of patients’ symptoms and conversational styles differ for men and women [24]. In the absence of evidence that patient choice accounts for gender differences in therapy [25], any differences in treatment between men and women at the level of primary care provides one with a valuable source of epidemiological information. Despite the fact that women use more health care services than men [26], our results suggest that women with ischaemic heart disease may receive significantly less secondary preventive therapies compared with their male counterparts, thus exposing them to a higher risk of myocardial infarction and death.

Since 1985 the mortality from ischaemic heart disease in Ireland has declined by 37% in men and by 30% in women. Similarly, the mortality from acute myocardial infarction has declined by 50% in men and 39% in women [3]. Lack of secondary preventive measures in women may be one reason for the slower decline in mortality seen in women. Increased prevention, diagnosis, and treatment efforts should be directed toward women in primary care.

One of the limitations of this study is the unavailability of a specific diagnosis of ischaemic heart disease in our population. However, whilst nitrate prescribing alone may be less sensitive than other methods of estimating the prevalence of ischaemic heart disease, its relatively high specificity means that the majority of patients who are prescribed nitrate therapy do indeed have established ischaemic heart disease. In addition, the prevalence of ischaemic heart disease in our population as estimated by nitrate prescriptions closely matches that reported in a recent epidemiological survey, which reported a prevalence of angina of 13% in men and 9% in women aged> 55 years [1]. Our results were unaltered whether patients with presumptive ischaemic heart disease were identified using acute or chronic nitrate therapy. While accepting that a diagnosis of ischaemic heart disease, based on the use of nitrates, may not be 100% accurate in this population, nonetheless the prescribers treating these patients believe their patients have ischaemic heart disease and should therefore prescribe appropriate secondary preventive therapy. Our data therefore reflect the reality of prescribing practice. Finally, the accuracy of our data was confirmed by the finding that no gender bias exists in the prescription of drugs that are not discretionary, such as insulin or antiepileptic therapy, in this group of patients.

A number of theories have been put forward to explain this differential care in women. As chest pain is more often associated with normal epicardial arteries in women than in men, physicians may believe that angina in women is less likely to be followed by serious cardiovascular events [27], and this may explain why physicians are more likely to attribute anginal symptoms in women to noncardiac causes [19]. Thus physicians may believe that angina is a benign symptom in women leading to less aggressive secondary preventive measures. Women are also less likely to attend cardiac rehabilitation following a myocardial infarct, which further reduces the opportunity to implement adequate secondary preventive measures that may have not have been performed in hospital [28].

Anxiety is common in patients with acute coronary syndromes, and may influence outcome, including sudden death in ischaemic heart disease [29]. Whilst anxiety is more commonly diagnosed in women [13], our results adjusted for this gender difference show a significantly greater use of anxiolytic benzodiazepines in women with established coronary heart disease. While the prescription of antidepressants is greater in women than in men, this was little affected by the presence of ischaemic heart disease. Our results may represent a gender bias in the perceived value of treating men and women with ischaemic heart disease, the former being given secondary prevention therapy and the latter offered symptomatic therapy.

We also found that the elderly were less likely to receive a statin, β-blocker or aspirin, suggesting that as previously noted [9], ageism also exists in our study population. This effect was even more significant in patients aged> 75 years. However, as older patients are more likely to have more severe disease and be treated medically rather than surgically, they would be expected to benefit more from important secondary preventive treatments. Whilst the reduced prescription of β-blockers in the elderly may be explained by a higher prevalence of chronic obstructive airways disease, the prescription of other secondary preventive therapies is more difficult to explain. Statin therapy has been shown to reduce coronary events and mortality in patients up to 75 years of age with average cholesterol [30]. One reason for the under-treatment of patients with statins may lie in the fact that current treatment guidelines stipulate an age limit of 75 years [31], or that older patients are largely excluded from major clinical trials [32], and as such will be under-represented in the evidence base used to determine clinical effectiveness. A recent exception is the Heart Protection Study, which included patients up to the age of 80 years [33]. It has also been suggested that implicit age-based prioritization policies are operating in health care [9]. As a result, physicians may exhibit caution when treating the elderly.

The overall prescribing of aspirin, β-blockers, ACE inhibitors and statins of 70%, 37%, 33% and 30%, respectively, compares with the recent EUROASPIRE II survey that reported that the use of aspirin was 86%, β-blockers 63%, ACE inhibitors 38% and lipid-lowering drugs 61% in patients with established coronary heart disease [34]. However, there has been a collective failure of medical practice in Europe to achieve the substantial potential among patients with coronary heart disease to reduce the risk of recurrent disease and death [35]. There is a need to improve the transfer of evidence gained from clinical trials to prescribers in an effective manner as there is evidence to suggest that the effectiveness of interventions aimed at improving drug-prescribing behaviours may be suboptimal [36]. Both women and the elderly need to be targeted to receive important secondary preventive therapy in an effort to reduce mortality.