Brendan Buckley, European Centre for Clinical Trials in Rare Diseases, University College Cork, Lancaster Hall, 6 Little Hanover Street, Cork, Ireland E-mail: email@example.com
In Ireland, cardiovascular disease is a major cause of death. However, blood pressure (BP) goal achievement is unsatisfactory. The authors aimed to document BP control and increase awareness. A total of 1534 patients were enrolled in the study, with a mean age of 64.7±11.9 years (53.8% women). Duration of hypertension was 8.7±7.7 years, and 14.6% had diabetes, 13.8% had coronary artery disease, and 40.5% were taking antihypertensive monotherapy. β-Blockers (39.8%), angiotensin-converting enzyme inhibitors (32.2%), and angiotensin receptor blockers (22.0%) were prescribed most frequently. Mean BP was 136.0±6.1 mm Hg/89.5±5.0 mm Hg in nondiabetic patients (48.6% <140/90 mm Hg) and 131.0±7.4 mm Hg/81.7±4.6 mm Hg in diabetic patients (16.7% <130/80 mm Hg). Diet, exercise, and lifestyle modifications (63.5%) were frequently recommended. Increased patient awareness and compliance together with the adherence of physicians to current guidelines and greater willingness to take action in patients with uncontrolled hypertension should help in improving BP control and thus reduce cardiovascular risk.
High blood pressure (BP) is a major risk factor for cardiovascular (CV) disease and affects about 30% of the adult population in the United States and Canada as well as up to 50% of adults in European countries.1 It is the leading cause of death globally, with more than 7 million deaths attributed to CV disease each year.2
Although many different effective drugs and drug classes are available,3 control rates are low.4 While between 40% and 50% of treated patients are well controlled in North America, control rates in Europe and Asian countries can be as low as 20%. This control rate is only the tip of the iceberg, however, as illustrated by a recent survey in primary care in Germany in which many patients with hypertension were previously undiagnosed.5 Many patients are underdiagnosed and undertreated in a primary care setting. A recent global survey has shown that this relates to partial inertia toward tight BP control on both the patient and physician side.6 As illustrated by a number of recent surveys in the United States, about one third of patients whose BP values are consistently above goal levels do not have medication started, changed, or increased.7–9 It can be overcome, however, as a recent article nicely summarized.10
By contrast with the situation in the United States, Europe, and the United Kingdom, there are limited contemporary data on the distribution of BP, the prevalence of hypertension, and the problem of treatment inertia in the ethnically and culturally more homogenous Irish population. This is more surprising since CV disease remains the primary cause of death in Ireland, although there is a positive trend for improvement.11 On the basis of data from England,12 it can be estimated that at least 50% of the population aged 50 years and older are hypertensive in Ireland. This estimate is further supported by data from the Cork and Kerry Heart Disease study, which documented a hypertension prevalence of 47% (480 of 1018 patients) for both men and women in primary care in 1997,13 with an age-dependent increase from an age of 50 until 69 years. Of these hypertensive patients, 38% (182 of 480) were known to be hypertensive and treated accordingly and less than half of these patients (41%) (74 of 182) had their BP controlled when being treated. The most recent data have been obtained in the 2007 Survey of Lifestyle, Attitudes, and Nutrition in Ireland (SLÁN) project in which 6 of 10 respondents had high BP, of which 6 of 10 were not taking medication and of which 7 of 10 were not controlled to BP levels <140/90 mm Hg (http://www.dohc.ie/publications/slan07_report.html).
Therefore, hypertension is one of the most common problems that Irish general practitioners have to manage and they are faced with considerable challenges when trying to adequately control BP.14 This was the rationale to set up the “i-target Ireland” Blood Pressure Goal Program, which was designed to collect data on the rate of BP control in patients with essential hypertension currently receiving antihypertensive treatment. The primary objective of the survey was to determine the proportion of hypertensive patients not achieving their BP goals on current treatment. Further objectives were to increase the awareness of the importance of BP goals set by international guidelines.
Patients and Methods
This was a cross-sectional survey conducted in primary care practices throughout Ireland. To recruit general practices, a conditioned random sample of 300 centers was drawn from a nationwide database. Physicians were asked to provide data of 20 consecutive patients in their care who were diagnosed with essential hypertension and had been receiving treatment with antihypertensive monotherapy or combination agents. The protocol and survey material was reviewed by the research ethics committee of the Cork Teaching Hospitals. Informed consent was obtained from each patient prior to enrollment.
Physicians completed a questionnaire during patients’ single routine visit to the practices. The following data were collected: (1) demographics: age, sex, duration of hypertension (years/months), smoking status, current office BP readings, and the date of visit. (2) Comorbidities: diabetes mellitus, metabolic syndrome, peripheral arterial disease, diabetic nephropathy, history of atrial fibrillation, history of myocardial infarction, obesity, coronary artery disease, congestive heart failure, history of stroke, other, or none of these. To ensure consistency across practices, comorbidity definitions and diagnostic criteria were provided along with the questionnaire. (3) Information on lifestyle modifications recommended in the past: weight loss, stop smoking, exercise, diet, other, or none. (4) Current antihypertensive medication. (5) BP targets with reference to use of specific BP guidelines and whether BP goals had been achieved in that patient. (6) The action that physicians deemed necessary to take in case BP goal was not achieved: increase dose, add another drug, prescribe combination therapy, prescribe new agent in monotherapy, lifestyle modification, or none.
BP control was defined as having the current BP measurement <140/90 mm Hg in nondiabetic patients and <130/80 mm Hg in diabetic patients in accordance with the guidance of the European Society of Hypertension/European Society of Cardiology (ESH/ESC) 2007. For each patient, physician-defined targets were compared with the values obtained during the BP measurement on the survey day. BP measurements were performed in accordance with recent recommendations.15 Readings, however, were only obtained once.
Statistical analysis was performed descriptively and was interpreted in an explorative way.
Of the initially contacted 300 primary care physicians, 76 agreed to participate (response rate, 25.3%). A total of 1542 patients were recruited in the study; 8 patients were excluded from the analysis due to nonadherence to the protocol (eg, nonhypertensive/no antihypertensive treatment). Therefore the final total sample size was 1534 (99.5%). These patients were the basis for the following analyses.
Participating patients had a mean age of 64.7±11.9 years, with 53.8% being women. All patients were hypertensive (inclusion criterion), with a mean duration of hypertension of 8.7±7.7 years. Mean current BP readings were 139.4±17.5 mm Hg systolic and 81.1±10.0 mm Hg diastolic.
Comorbidities in Treated Hypertensive Patients
Figure 1 displays the comorbidity burden of hypertensive patients included in the study. Diabetes mellitus was the most frequent comorbidity (14.6%), followed by coronary artery disease (13.8%) and a history of atrial fibrillation (8.0%). A total of 66.4% of patients had at least 1 comorbidity and 26.3% had ≥2 comorbidities. Furthermore, 13.1% were current smokers, and 7.4% had the metabolic syndrome.
BP Goal Achievement
Of this cohort, 48.6% of nondiabetic patients achieved BP target of <140/90 mm Hg and only 16.7% of patients with diabetes were controlled using the goal of <130/80 mm Hg recommended in the ESH/ESC guidelines (Figure 2). Given that more than 2 of 3 (83.3%) patients with hypertension and diabetes had uncontrolled BP underlines that BP goal achievement was highly dependent on whether a patient was diabetic or not.
BP goal achievement was also assessed based on individual (not as per guideline) targets set by physicians: 40.1% of nondiabetic and 54.7% of diabetic patients were perceived to be adequately controlled despite a proportion of these patients missing the guideline-recommended BP goals. Therefore BP goal achievement was underestimated in nondiabetic (40.6% vs 48.6%; Δ=−8.0%) and grossly overestimated in diabetic patients (54.7% vs 16.7%; Δ=−38.0%).
Antihypertensive Drug Utilization
A total of 40.5% of patients were taking monotherapy and 59.5% received either free or fixed combinations of antihypertensive drugs (Figure 3). Renin-angiotensin system (RAS)–blocking agents were most frequently used (32.2% angiotensin-converting enzyme [ACE] inhibitors and 22.0% angiotensin receptor blockers [ARBs]). A total of 39.8% of patients received β-blockers. Combinations of diuretics with ACE inhibitors or ARBs were chosen in 6.6% and 8.0% of patients, respectively. ACE inhibitors together with calcium channel blockers (CCBs) were used in 1.2% of patients.
Use of Guidelines
In the present survey, most Irish physicians indicated use of the British Hypertension Society Guidelines to a large extent (54%), followed by the guidance of the ESH/ESC (38%). Six percent referred to even more localized guidance (including no guidance), and only 2% to those of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).
Action Taken to Control BP
Figure 4 displays the actions that physicians took when faced with uncontrolled BP. In the top panel, the total number of patients is displayed. For 57.5% of these patients, no action was taken because the physician considered the BP to be on target (which did not mean guideline goals were met). In the bottom panel, only patients with uncontrolled BP (using the physicians’ perspective) are displayed. The most frequent recommendations were diet, exercise, and lifestyle modifications (63.5%). In 20.2% of patients, the dose of antihypertensive drug was increased and 17.4% of patients were reviewed, referred, encouraged to comply, or had ambulatory BP measurement performed.
A recent global survey of 1259 primary care physicians in 17 countries worldwide reported a gap between clinical practice and recent recommendations in hypertension management.6 The survey showed that physicians believed that 62% of their patients had their BP controlled and 86% said they agreed with the guideline-recommended BP goals, but 41% still aimed to reduce BP to unspecified “acceptable” levels only. The present survey essentially confirms these observations for Ireland, a country that did not take part in the global survey. BP goals enforced by recent guidelines16–18 were well-known, but patients were allowed to have higher BP readings in many cases. This is the more alarming finding, as data from the recent European Union Heart Index have shown that Ireland ranks 16 out of 29 countries, owing to not meeting the requirements for quick access to heart treatment.19 The authors suggested that there should be a stronger emphasis on cardiac prevention, such as a national screening program, BP monitoring, and compulsory exercise in schools.
BP Goal Achievement
The Kilkenny Health Project carried out a baseline population health examination study in County Kilkenny from 1985 to 1992.20 Risk factors were compatible with the high mortality rates in Ireland at that time. BP levels were also high. Average levels were 146/79 mm Hg in men and 142/78 mm Hg in women. The prevalence of hypertension (at that time defined as either ≥160 mm Hg systolic and/or ≥95 mm Hg diastolic, or taking antihypertensive treatment) ranged from 8% in men aged 35 to 44 years to 40% in men aged 55 to 64 years and from 4% to 52% in women. Previous data from primary care are available from the Cork and Kerry Heart Disease study (1997)13 in which prevalence of hypertension was 47%. A total of 38% were taking antihypertensive medication and only 41% of these patients were actually controlled <140/90 mm Hg. Studies in different countries, however, have shown that BP control rates may be as low as 18.0% (Taiwan), 19.8% (Turkey), or 21.8% (Mexico), but may even reach 53.1% (United States) or 55.7% (Japan) in other countries.4
Although the numbers are not directly comparable, the data from the present study document an improvement in BP control, with 48.6% of nondiabetic patients reaching BP values <140/90 mm Hg. Diabetic patients, however, are controlled to a much lesser extent, with 83.3% having a BP reading >130/80 mm Hg on the day of the survey. While these measurements were usually carried out once and actual values may have been influenced by the study setting, the situation is clearly not acceptable given that every further reduction can reduce morbidity and mortality to a considerable extent.21 Indeed, even a 2-mm Hg lower usual systolic BP would involve about 10% lower stroke mortality and about 7% lower mortality from ischemic heart disease or other vascular causes in middle age on a population level.21
Given that multiple risk factors merge into the absolute CV risk of a given patient, the control rates mentioned above are certainly optimistic estimates of appropriate BP control in the Irish population. Guidelines such as those from the ESH/ESC 200716 highlight the need for a risk-adapted approach to BP control. Multiple risks including organ damage, diabetes, and established cardiovascular and renovascular disease lower the targets for BP control and will thus increase the number of patients who currently have uncontrolled BP. Therefore, a vital role of physicians in primary care is the assessment of CV risk together with an adapted–BP-lowering strategy.
Antihypertensive Drug Utilization
Although there was a large variation in the use of different drug classes among physicians participating in this survey, β-blockers and RAS-blocking agents were heavily used in general, although current evidence assigns a class 2 recommendation for β-blockers only. The recent 2006 National Institute for Health and Clinical Excellence (NICE) guidance on hypertension states that calcium channel blockers and diuretics are first-line drugs in hypertensive patients 55 years and older while ACE inhibitors should be used in patients younger than 55 years. The British Hypertension Society (BHS) considers β-blockers to be indicated in myocardial infarction and stable heart failure (compelling indication). In patients with diabetes or the metabolic syndrome, β-blockers have been documented to either promote the development of diabetes or a worsening of blood sugar control. An excellent overview has summarized the evidence for or against the use of β-blockers.22
The more surprising is the frequent use of β-blockers in Ireland. A recent drug utilization study investigated the use of antihypertensive drugs in 6 countries throughout Europe.3 Finnish and Swedish patients received β-blockers in 25% of cases, with a substantially lower use in Denmark (10%). Compelling indications16 may account in part for the frequent use of β-blockers in Ireland such as previous myocardial infarction (7.2%), angina pectoris (coronary artery disease 13.8%), history of atrial fibrillation (8.0%), and congestive heart failure (3.2%). The use of RAS-blocking agents was between 42% and 60%, which is well compatible with the data obtained in Ireland (54.3%).
A total of 40.5% of patients received antihypertensive monotherapy, although the majority of patients had uncontrolled BP despite being on treatment. Guidelines like the ones of the ESH/ESH 200716 recommend to escalate to combination therapy after full-dose monotherapy has failed or as first-line therapy in patients with marked BP elevation (systolic >160 mm Hg or diastolic > 100 mm Hg) and/or high or very high CV risk. In patients with uncontrolled hypertension, however, only 19% either received an additional drug or combination was prescribed in the present survey.
Overall treatment rates with monotherapy or combination therapy are comparable for Ireland and the United States, for example, where 42% of patients receive only 1 drug while the rest receive any drug combination.23 The necessary escalation of drug therapy into drug-drug combinations is, however, not well appreciated by physicians in this Irish survey. Bramlage and colleagues6 reported that physicians from a variety of countries in Europe indicated a switch to combination therapy in 74% of patients where monotherapy failed (51% would receive additional treatment, 23% would receive fixed-dose combinations).
Use of Guidelines
Guidance for the treatment of hypertension can be obtained from various sources.16–18 International guidelines, however, are not able to consider local laws and regulations and the reimbursement situation in a certain country. Guidance is also frequently tailored for specialists in hypertension treatment and not so much directed toward general practitioners who may need more straight recommendations to consider in their daily complex task of screening and treating patients for all sorts of diseases. There are initiatives in certain European countries to adapt guidelines for general practitioners aiming at simplifying treatment schemes and improving control rates. In the United States, where guidelines such as JNC 7, which are recently directed toward primary care providers, give clear instructions on which drug class is to be used as initial therapy and the selection of drugs for the compelling indications, control rates in treated hypertensive patients are particularly good.
Physicians in Ireland tended to adhere to British Hypertension Guidelines in the past because Ireland doesn’t have its own national hypertension guideline. Indeed, in the present survey, most Irish physicians indicated use of the British Hypertension Society Guidelines (54%). These numbers are compatible with data from a global survey,6 which indicated that local guidelines are most commonly used (32% for the subset of European countries). Given that these guidelines generally recommend BP goals of <140/90 mm Hg and <130/80 mm Hg in diabetic patients, while most patients do not achieve this goal, it can be questioned whether these actually meet the needs for most physicians. This, in turn, raises the question of whether control rates would improve if Ireland had its national guideline. Based on the aforementioned lack of quick access to heart treatment and the need for a stronger emphasis on cardiac prevention,19 together with the fact that CV disease remains the primary cause of death in Ireland,11 there is an apparent need for a guideline that considers the specific morbidity burden and access to health care in Ireland.
Action Taken to Control BP
The action to be taken if BP control is not sufficient is obvious and steps to take should be illustrated in all guidelines.16–18 BP control rates in clinical trials approach 80%,24,25 and from this perspective it is not clear why BP control is as low as 20% to 30% in several primary care studies,5 including the present one. The setting of a clinical trial, however, is characterized by a pre-selection phase that enforces compliance on the patient side, where patients and physicians are tightly monitored, physicians follow rigorous protocols, and treatment duration is in many cases shortened. The situation in primary care is characterized by much lesser control. Inappropriate patient education leads to lack of understanding the consequences of uncontrolled BP, thus patients either forget to pick up their prescription or to take their medication. Physicians on the other hand are satisfied by near-normal BP control, usually treating multimorbid patients with a number of different drugs and indications. To up-titrate medication is obviously not enough to get a patient’s BP to goal.
Physicians in the present survey largely refer to diet, exercise, and lifestyle modification if BP is not controlled (63.5%) on monotherapy or combination therapy. While these are principally beneficial and important measures to support the adjustment of BP, they have proven to be largely ineffective in clinical practice. On the other hand, dose is increased in 20.2% of cases, another drug added in 11.1%, a combination prescribed in 7.3%, and a new agent installed in 5.2% (total 43.8%). Given that BP goals are not achieved to a large extent, diet, exercise, and lifestyle changes alone are clearly not the optimal therapeutic choices for patients taking failing antihypertensive monotherapy.
These facts have been well recognized in Ireland, and “Heartwatch” is a currently running secondary prevention program in Ireland involving almost 13,000 patients in general practice with the aim of reducing morbidity and mortality due to CV disease. After 1-year progress of the program, a statistically significant improvement in the control of (identifiable) risk factors (systolic BP, diastolic BP, total cholesterol, low-density lipoprotein cholesterol, and smoking) was reported, indicating benefits for patients directly involved. An improvement in systolic BP was reported in 22.8% of patients, and an improvement in diastolic BP was reported in 47.8% of patients.26
Another step forward in the prevention of CV disease and in improving BP control in Ireland, particularly in diabetic patients, would be a close cooperation of general practitioners in primary care with specialists. To improve the cooperation, triggers have to be defined that result in a referral if certain BP goals are not achieved in a given period.
The interpretation of the current survey is limited by the fact that the BP readings have only been obtained once (in-office). This may have resulted in an on-average slightly higher BP reading but would not qualitatively change the low control rates. Further, there is no information regarding the dose of the drugs prescribed, which may interfere with the degree of BP control. Although adherence and persistence are key issues in antihypertensive management, these parameters have likewise not been obtained due to the cross-sectional design. A strength of the study is the cross-sectional design with a considerable number of general practices throughout Ireland, which should provide a realistic estimate of BP control in Ireland. The response rate of 25.3% is higher as in similar surveys27 but may still overestimate the proportion of patients treated to target.
BP control while taking antihypertensive treatment in primary care in Ireland is not optimal or in line with guideline-provided goals since less than half (48%) of nondiabetic patients and less than one third (18%) of diabetics achieved BP goal. The reasons for this discrepancy are multidimensional. One aspect is the type and dose of antihypertensive treatment prescribed. There is room for improvement using fixed combinations of well-tolerated drugs with a high persistence on treatment. Another aspect is to embed the effort to reduce BP into a more comprehensive approach to prevent the incidence of CV disease. An increase in patients’ awareness and compliance together with an increased adherence of physicians to current guidelines should help in reducing the long-term CV consequences of hypertension.
Disclosures: This study was funded by an unrestricted educational grant provided by Sanofi-Aventis Ireland. The preparation of the manuscript was supported by a grant from Sanofi-Aventis Ireland to PB. All authors take full responsibility for the content of the article, the interpretation of the data, preparation, review, and approval of the manuscript. BB, ES, NC, TF, PB, and IJP have been participants at advisory board meetings at Sanofi-Aventis. ET is a former employee of Sanofi-Aventis Ireland.