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Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

J Clin Hypertens (Greenwich). 2010;12:666–677. ©2010 Wiley Periodicals, Inc.

Hypertensive patients with cardiovascular (CV) comorbidities are at increased risk, and cardiologists’ care should put particular emphasis on controlling blood pressure. Data on blood pressure treatment and control and drug utilization on a global scale, however, are scarce. Aiming to resolve this lack of information, the authors analyzed the data of International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients With Hypertension (i-SEARCH) to gain further insights into national and regional blood pressure control and antihypertensive pharmacotherapy prescribed in cardiology practice. A total of 22,282 patients with hypertension from 26 countries were enrolled in 2005/2006. A total of 18,652 patients were treated (mean age, 63.0±11.4 years; 52.2% male; mean body mass index, 28.9 kg/m2). Mean systolic blood pressure was 148.2±19.8 mm Hg and diastolic blood pressure was 86.7±11.6 mm Hg. Blood pressure was controlled in 8.3% of diabetic and 25.3% of nondiabetic patients (21.2% overall), with particularly good control rates in North and Latin America (28.0% and 30.6%, respectively). A total of 31.2% of patients were treated with 1, 39.7% with 2, and 29.1% with ≥3 drugs. β-Blockers were being used most frequently (47.9%), in both monotherapy and combination therapy despite low numbers of patients with respective compelling indications for their use. The present data illustrate the potential for an improvement of blood pressure treatment and control in daily cardiology practice.

Hypertension is responsible for the majority of CV morbidity and mortality worldwide1 and is one of the most important reasons for office visits to physicians.2 It has also been regarded as a barometer for the quality of a health care system.3 Despite the availability of a large number of effective and well-tolerated antihypertensive drugs,4 however, blood pressure (BP) control rates are not satisfactory on a national and global scale.5–8 This holds especially true for the general population in Europe compared with the Americas.9

Efforts to effectively improve BP control should be based on an in-depth knowledge of patient characteristics and the relative contribution of the treating physicians.10 Therefore, the role of physicians’ attitudes and practice patterns (detection, treatment, and management of hypertension) has received increased attention.3,11,12 We have recently reported results from a survey in 1259 primary care physicians worldwide,8 showing that (1) physicians tend to overestimate control rates; (2) physicians make only limited efforts to control BP at BP values close to normal, although the elevated CV risk of hypertension was acknowledged; and (3) there is a lack of awareness on the patient side, being responsible for the apparent mismatch between hypertension treatment efforts and control rates.8 An important but obviously largely neglected aspect of this, however, is the choice and intensity of antihypertensive treatments in routine care. To our knowledge, there are no or only regionally restricted major drug utilization studies that directly link the patient’s diagnosis to actual treatment patterns.13

In aiming to provide such data, we analyzed recent cross-sectional data from the International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients With Hypertension (i-SEARCH) to address the following questions: (1) What are the BP control rates in cardiology practice across a number of countries and regions worldwide; (2) what are the BP control rates in relation to concomitant CV risk factors and comorbidities; and (3) what kind of antihypertensive drug treatments are prescribed in relation to concomitant risk factors and disease.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Eligible patients were male and female outpatients, 18 years or older, treated by a cardiologist, with currently treated or newly diagnosed arterial hypertension, defined as a seated systolic/diastolic BP of ≥140/90 mm Hg by sphygmomanometry or automated validated devices after 5 minutes of rest on the day of the study visit. Patients with acute fever (>38°C), renal disease (serum creatinine >20 mg/L), or concomitant urinary tract infection; those receiving treatment with cimetidine; those having undertaken strenuous physical activity in the preceding 24 hours; and women who were pregnant or menstruating were ineligible (the study was conducted to assess the prevalence of microalbuminuria and these factors increase the likely presence of false-positive results for microalbuminuria). Institutional and ethical review board approval for the study was granted for all participating centers, and all patients gave written informed consent to study participation. The study was conducted in accordance with the ethical principles of the current Declaration of Helsinki and consistent with the International Conference on Harmonization Good Clinical Practice.

Study Design and Procedures

This was an international observational survey in which patients were evaluated during a single visit. To allow extrapolation of results to the broadest possible population, the physician selection procedure took into account geographic aspects in each country (West/East, South/North, urban/suburban/rural) and physician profile (office/hospital).

For the subsequent comparison of global hypertension control, participating countries were clustered into regions: Northern Europe (Belgium, Germany, Sweden, Switzerland), Southern Europe (Greece, Italy, Spain, Turkey), Europe (Northern and Southern Europe), North America (Canada), Middle East (Kuwait, Lebanon, Qatar, Saudi Arabia, United Arab Emirates), and Asia (Hong Kong, Indonesia, Korea, Singapore, Taiwan, Thailand, Vietnam).

At each site, consecutive patients fulfilling the eligibility criteria were invited to participate in the study. Once enrolled, the following measurements were carried out on each patient: heart rate, urinary albumin and creatinine concentrations, and waist and hip circumferences. Results from these assessments were entered on each patient’s case report form, together with demographic data, CV history, and presence of CV risk factors, comorbidities, symptoms and signs of CV disease, and current chronic drug therapy. Levels of cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, C-reactive protein, and serum creatinine were included if they were assessed fewer than 12 months ago.14

Definitions

BP control was defined as a random BP reading of ≤140/90 mm Hg in nondiabetic and ≤130/80 mm Hg in diabetic patients. CV comorbidities included a history of stroke, myocardial infarction (MI), coronary artery disease (CAD), left ventricular hypertrophy (Sokolov-Lyon index >35 mm), congestive heart failure, and atrial fibrillation. CV risk factors included diabetes mellitus, current smoking, known hyperlipidemia, a body mass index (BMI) >30 mg/m2, and a family history of CAD/MI. Diagnoses were based on the investigator’s assessment and were not further validated within this study.

Statistical Analyses

Population characteristics that included demographics, medical history, nature, duration and severity of disease, comorbidities, and current or no treatment were summarized into means and standard deviations (SDs) for continuous variables and percentages (95% confidence intervals [CIs]) for categoric data.

A linear model was used to estimate the least square means of BP or number of antihypertensive treatment drugs according to region, adjusted for age, sex, diabetes, or plus number of comorbidities. A logistic regression analysis was conducted to estimate the BP control rate (adjusted probabilities) according to region, adjusted for age, sex, and diabetes, using predictive marginal probabilities. Continuous variables are depicted as adjusted means (least squares means) ± SDs and categoric variables as percentages (95% CIs).

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Study Population and Physician Profile

The primary analysis population consisted of 18,652 patients receiving pharmacotherapy for the treatment of hypertension and who had a complete dataset for this analysis (91.3% of the total sample). Reflecting the global nature of this study, patients were enrolled from 26 countries in Northern (n=5655) and Southern Europe (n=6655), North America (n=1455), Latin America (n=1560), the Middle East (n=570), and Asia (n=2757). A total of 76.4% of physicians were cardiologists and 22.3% were internists. Just over a third (34.1%) of physicians were office-based only, 23.4% were hospital-based only, and 42.5% were both.

Patient Demographics and CV History

The demographics, laboratory values, and CV history of the primary analysis population by region and in total are summarized in Table I. Mean age was 63.0±11.4 years, 52.2% were men, mean BMI was 28.9±5.8 kg/m2, and mean waist circumference 99.5±14.3 cm. A total of 24.3% had type 2 diabetes with an average duration of 7.9±7.6 years, 24.2% had CAD, 28.1% had a respective family history of CAD, 48.7% had hyperlipidemia, and 37.9% were current/former smokers.

Table I.   Demographics and Cardiovascular History at Study Entry (Primary Analysis Population) by Region and in Total
 Total (N=18,652)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as mean ± SD or percentage (95% confidence interval). Abbreviations: AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CVD, cardiovascular disease; LVH, left ventricular hypertrophy; MAU, microalbuminuria; MI, myocardial infarction; PAD, peripheral arterial disease; SD, standard deviation; WC, waist circumference.

Demographic characteristics
 Age, y63.0±11.4 64.9±11.0 62.5±11.4 65.7±11.362.7±11.8 57.1±11.360.5±11.1
 Men 52.2 (51.5–52.9)53.0 (51.7–54.3)52.9 (51.7–54.1)56.3 (53.8–58.9)46.4 (43.9–48.9)61.0 (57.0–65.0)48.5 (46.6–50.3)
 BMI, kg/m228.9±5.8 29.7±6.7 29.2±5.1 30.2±6.528.4±4.9 29.8±5.425.9±4.1
 WC, cm99.5±14.3102.5±14.8100.9±13.6102.6±15.197.0±12.1102.5±14.389.5±10.5
Selected risk factors for CVD
 Diabetes, 24.3 (23.7–25.0)29.6 (28.3–30.8)20.7 (19.7–21.8)29.0 (26.7–31.4)19.8 (17.8–21.8)29.7 (25.7–33.6)21.2 (19.7–22.8)
 DM duration, y 7.9±7.6  8.2±8.2  8.1±7.2  9.1±8.0 8.8±8.3  7.8±6.1 5.9±6.0
 Family history of CAD28.1 (27.4–28.7)29.9 (28.7–31.1)25.3 (24.2–26.3)49.9 (47.3–52.5)30.3 (28.0–32.6)39.5 (35.4–43.5)15.8 (14.3–17.1)
 Current/former smoker37.9 (37.1–38.6)36.4 (35.1–37.7)41.8 (40.5–43.2)55.7 (53.0–58.4)28.6 (26.3–30.9)44.9 (39.8–50.0)28.5 (26.7–30.2)
 Hyperlipidemia 48.7 (47.9–49.5)53.0 (51.5–54.5)43.3 (41.9–44.8)64.4 (61.6–67.3)45.4 (42.8–48.0)56.1 (50.7–61.5)46.1 (44.2–48.0)
 MAU58.5 (57.8–59.2)54.3 (53.0–55.6)59.6 (58.4–60.8)53.8 (51.3–56.4)57.5 (55.1–60.0)71.6 (67.9–75.3)64.7 (63.0–66.5)
Comorbidities
 LVH14.3 (13.5–15.0)8.5 (7.2–9.8)16.0 (14.7–17.3)6.1 (3.4–8.8)15.0 (12.3–17.8)26.0 (20.6–31.4)16.8 (14.8–18.7)
 CAD24.2 (23.6–24.8)21.1 (20.0–22.1)23.0 (22.0–24.0)40.3 (37.8–42.8)19.9 (18.0–21.9)28.4 (24.6–32.2)26.4 (24.8–28.1)
 CHF6.0 (5.7–6.4)6.0 (5.4–6.7)6.6 (6.0–7.2)4.9 (3.8–6.0)4.1 (3.1–5.1)8.3 (6.0–10.5)6.0 (5.1–6.8)
 AF8.5 (8.1–9.0)9.3 (8.6–10.1)10.6 (9.9–11.4)11.4 (9.8–13.1)4.1 (3.1–5.1)4.5 (2.7–6.2)3.8 (3.1–4.5)
 History of MI31.2 (30.2–32.3)24.4 (22.7–26.1)34.1 (32.3–35.9)41.7 (38.2–45.2)27.1 (23.6–30.7)27.9 (22.7–33.1)37.2 (33.8–40.5)
 History of stroke4.6 (4.3–4.9)4.4 (3.9–4.9)4.7 (4.2–5.2)5.5 (4.3–6.7)4.6 (3.6–5.7)3.9 (2.3–5.5)4.4 (3.7–5.2)
 PAD4.5 (4.2–4.8)6.1 (5.4–6.7)5.0 (4.4–5.5)5.7 (4.5–6.9)2.6 (1.8–3.4)4.7 (2.9–6.5)0.5 (0.2–0.7)

The following differences between the 6 regions were noteworthy: BMI and waist circumference were substantially lower in Asia compared with other regions. The proportion of patients with diabetes was particularly low in patients from Southern Europe, Latin America, and Asia. A family history of CAD and smokers were highly prevalent in North America and the Middle East compared with the other countries. CAD and hyperlipidemia were particularly prevalent in North America.

Hypertension Control

Table II shows the hypertension control rate across the 6 regions, overall and separately, for patients with or without diabetes. Data were adjusted for differences in baseline characteristics as indicated. The patients showed a mean systolic BP of 148.2±19.8 mm Hg and a diastolic BP of 86.7±11.6 mm Hg with a mean duration of hypertension of 9.0± 7.5 years. In 21.2% of patients, overall BP was controlled, less so in patients with diabetes (8.3%) in whom lower BP targets applied (<130/80 mm Hg).

Table II.   Hypertension Control by Region and in Total
 Total (N=18,622)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as mean ± SD or percentage (95% confidence interval). Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure. aP<.0001 for comparison between regions. bAdjusted for age, sex, and diabetes mellitus. cAdjusted for age and sex.

Hypertension
 Duration, y  9.0±7.5  9.8±7.7a  8.4±6.6a 11.7±9.6a 10.5±8.9a  6.9±5.8a 7.47±6.5a
 SBP, mm Hgb148.2±19.8151.4±0.3a148.6±0.3144.4±0.5a,b140.9±0.5a,b156.6±0.9a,b145.5±0.4a,b
 DBP, mm Hgb 86.7±11.6 87.8±0.2a,b 87.1±0.2a,b 81.6±0.3a 83.3±0.3a 92.3±0.5a 84.6±0.3a
 SBP controlledb25.2 (24.6–25.8)17.5 (16.5–18.6)23.9 (22.9–25.0)32.5 (30.0–35.1)38.3 (35.9–40.7)12.2 (9.7–15.3)29.4 (27.7–31.1)
 DBP controlledb42.5 (41.8–43.3)35.3 (34.0–36.6)38.5 (37.3–39.8)61.9 (59.2–64.6)51.9 (49.3–54.5)26.5 (22.6–30.9)48.4 (46.4–50.4)
 BP controlledb21.2 (20.6–21.8)13.4 (12.5–14.4)19.6 (18.7–20.7)28.0 (25.6–30.5)30.6 (30.6–33.0)9.6 (7.4–12.5)24.3 (22.7–26.0)
Hypertension with diabetes, ≥130/80 mm Hg
 SBP controlledc12.9 (11.9–13.9)9.6 (8.3–11.2)12.0 (10.3–13.9)21.9 (18.2–26.2)17.0 (13.1–21.7)5.8 (3.0–10.8)17.2 (14.3–20.5)
 DBP controlledc23.4 (22.2–24.7)18.2 (16.4–20.2)17.8 (15.7–20.0)44.1 (39.2–49.0)23.9 (19.4–29.1)15.3 (10.0–22.7)32.9 (29.1–37.0)
 BP controlledc8.3 (7.5–9.1)5.4 (4.4–6.7)7.5 (6.2–9.1)17.5 (14.1–21.5)9.4 (6.5–13.2)5.8 (2.9–11.1)11.9 (9.5–14.8)
Hypertension without diabetes, ≥140/90 mm Hg
 SBP controlledc29.1 (28.4–29.9)21.0 (19.7–22.3)28.9 (27.6–30.2)36.6 (33.6–39.7)44.1 (41.3–46.9)15.2 (11.9–19.3)34.4 (32.4–36.5)
 DBP controlledc48.7 (47.8–49.5)41.8 (40.2–43.4)46.1 (44.6–47.5)66.6 (63.5–69.5)60.5 (57.6–63.2)31.4 (26.5–36.7)54.0 (51.9–56.2)
 BP controlledc25.3 (24.6–26.0)17.4 (16.3–18.7)25.3 (24.1–26.6)32.8 (30.0–35.8)38.8 (36.1–41.6)12.0 (9.0–15.8)30.3 (28.4–32.3)

Differences between regions were considerable for control rates, which were higher in North and Latin America (28.0/30.6%) compared with the other countries, of which Europe (19.6%) and the Middle East (9.6%) had particularly low control rates. Consistent with this, mean BP readings were lower/higher in these respective countries.

Table III shows BP control rates in participating countries worldwide. Even after adjusting for age, sex, and diabetes, differences were substantial, with particularly high control rates in Hong Kong (51.8% [95% CI, 40.3–63.1]) and Korea (39.9% [95% CI, 34.3–45.8]). Low control rates were observed in Lebanon (1.7% [95% CI, 0.8–3.8]) and Vietnam (8.0% [95% CI, 5.9–10.7]).

Table III.   Blood Pressure Control Rates in Participating Countries Worldwidea
CountryCrude Odds Ratio (95% CI)Adjusted Odds Ratio (95% CI)
  1. Abbreviation: CI, confidence interval. aPrevalence rates are crude and adjusted for differences in age, sex, and the presence of diabetes.

Belgium19.8 (16.4–23.2)17.9 (15.0–21.3)
Canada28.5 (26.2–30.9)28.0 (25.6–30.5)
Germany11.8 (10.9–12.9)11.7 (10.7–12.7)
Greece24.1 (22.3–25.9)21.5 (19.8–23.3)
Hong Kong53.9 (72.8–64.9)51.8 (40.3–63.1)
Indonesia14.2 (11.3–17.2)12.5 (10.1–15.4)
Italy23.9 (20.4–27.4)21.7 (18.6–25.3)
Korea42.9 (37.1–48.7)39.9 (34.3–45.9)
Kuwait00
Lebanon1.8 (0.4–3.3)1.7 (0.8–3.8)
Mexico29.2 (25.3–33.1)28.9 (25.1–33.0)
Peru38.4 (33.8–42.9)35.7 (31.3–40.4)
Qatar00
Saudi Arabia18.2 (9.6–26.8)17.3 (10.2–27.9)
Singapore22.3 (14.6–30.0)22.3 (15.4–31.1)
Spain22.2 (20.3–24.0)20.9 (19.1–22.8)
Sweden21.7 (17.6–25.7)19.3 (15.8–23.4)
Switzerland22.4 (17.6–27.2)20.1 (15.9–24.9)
Taiwan34.1 (30.8–37.4)32.0 (28.9–35.4)
Thailand28.2 (24.3–32.0)28.5 (24.6–32.7)
Turkey16.9 (15.0–18.7)15.0 (13.4–16.8)
United Arab Emirates34.0 (24.6–43.6)35.6 (26.2–46.4)
Vietnam9.7 (6.9–12.5)8.0 (5.9–10.7)

Hypertension Control in Relation to Concomitant Risk Factors and Comorbidity

BP control decreased with increasing numbers of risk factors overall and in most regions worldwide (23.5% in patients with 1 risk factor and 13.6% in patients with ≥3 risk factors) (Table IV). While patients with prior myocardial infarction had particularly good BP control (24.4% vs 17.9%), control rates decreased in the presence of left ventricular hypertrophy and were essentially unchanged in patients with atrial fibrillation or prior stroke. Overall, the degree of control increased with increasing numbers of comorbid diseases.

Table IV.   Blood Pressure Control With Respect to Concomitant Risk Factors and Comorbidity, Adjusted for Age, Sex, and Diabetes Mellitus
 Total (n=18,652)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as percentage (95% confidence interval).

No. of risk factors
 123.5 (22.5–24.6)14.3 (13.2–16.5)22.4 (20.7–24.2)26.5 (22.5–31.0)33.3 (29.6–37.3)10.7 (6.8–16.4)30.9 (28.1–33.9)
 218.9 (17.8–20.0)11.3 (9.8–13.0)17.3 (15.5–19.3)24.9 (21.0–29.1)29.6 (25.3–34.2)8.3 (5.0–13.7)21.4 (18.2–24.9)
 ≥313.6 (12.3–14.9)8.1 (6.5–10.0)10.2 (8.3–12.5)23.3 (19.2–27.9)15.9 (11.3–21.9)6.8 (3.3–13.2)19.4 (14.3–25.7)
Stroke
 (−)21.2 (20.6–21.9)13.2 (12.3–14.2)19.7 (18.7–20.8)28.3 (25.8–30.8)30.7 (28.3–33.1)9.6 (7.3–12.6)24.1 (22.5–25.8)
 (+)20.7 (17.9–23.5)16.7 (12.3–22.1)17.5 (13.5–22.5)24.0 (15.7–35.0)27.1 (17.9–38.7)16.5 (5.3–40.7)26.8 (19.6–35.5)
Myocardial infarction
 (−)17.9 (16.8–18.9)11.4 (10.0–13.0)16.2 (14.4–18.1)27.5 (23.4–32.1)29.6 (25.4–34.2)6.2 (3.5–10.6)21.4 (18.4–25.2)
 (+)24.4 (22.5–26.3)16.8 (13.8–20.3)22.2 (19.0–25.7)31.9 (26.6–37.7)26.5 (20.0–34.4)14.3 (7.2–26.3)23.1 (18.5–28.4)
Atrial fibrillation
 (−)21.2 (20.5–21.8)13.4 (12.5–14.4)19.4 (18.3–20.5)27.6 (25.1–30.3)30.7 (28.3–33.1)10.3 (7.8–13.4)24.4 (22.7–26.1)
 (+)21.1 (19.0–23.2)11.5 (8.9–14.6)22.3 (19.0–25.9)31.1 (24.2–38.9)26.5 (17.2–38.5)NA24.3 (16.9–33.5)
Left ventricular hypertrophy
 (−)20.7 (19.7–21.7)11.9 (10.4–13.7)20.7 (19.1–22.4)25.6 (20.6–31.3)30.7 (26.9–34.7)5.1 (2.6–9.5)20.7 (18.4–23.1)
 (+)15.5 (13.3–17.7)10.4 (6.3–16.8)11.7 (8.9–15.1)4.5 (0.6–26.6)26.7 (18.7–36.6)3.3 (0.8–12.6)17.3 (12.8–22.9)
No. of comorbid diseases
 120.8 (19.5–22.1)13.6 (11.6–15.9)18.5 (16.4–20.8)30.3 (25.4–35.6)27.9 (23.0–33.4)5.4 (2.6–10.9)24.2 (20.9–27.8)
 222.9 (21.2–24.7)15.5 (12.8–18.7)22.2 (19.3–25.5)29.5 (24.4–35.3)27.4 (20.8–35.1)11.3 (5.1–23.1)21.4 (17.2–26.2)
 ≥322.3 (19.3–25.2)17.6 (12.7–23.8)17.8 (13.8–22.6)29.9 (20.9–40.7)33.7 (21.7–48.3)13.0 (4.2–33.7)21.5 (14.7–30.2)

Number and Type of Antihypertensive Agents

Table V shows the number of antihypertensive agents according to control of hypertension and presence of diabetes, CV risk factors, and disease. A total of 31.2% of patients were treated with 1, 39.7% with 2, and 29.1% with ≥3 drugs. The degree of combination therapy use was higher in North America, Asia, and the Middle East.

Table V.   Medical Treatment in Patients With Hypertension by Region and in Total
 Total (N=18,652)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as percentage (95% confidence interval). Abbreviations: CI, confidence interval; SD, standard deviation. aAdjusted for age, sex, diabetes mellitus, and number of comorbidities. bP<.0001 for comparison of respective regions vs rest of the world. cP<.05 for comparison of respective regions vs rest of the world. dP<.01 for comparison of respective regions vs rest of the world. eAdjusted for age, sex, and number of comorbidities. fAdjusted for age, sex, and diabetes mellitus.

Any antihypertensive treatment
 1 druga31.2 (30.5–31.8)32.2 (30.9–33.5)b30.7 (29.6–31.9)27.4 (25.1–29.9)c30.4 (28.1–32.8)23.5 (20.0–27.5)d25.5 (23.9–27.2)b
 2 drugsa39.7 (39.0–40.4)35.7 (34.5–37.0)b40.8 (39.5–42.0)c39.0 (36.5–41.6)40.9 (38.4–43.4)40.5 (36.2–44.9)44.5 (42.6–46.4)b
 ≥3 drugsa29.1 (28.4–29.8)29.9 (28.7–31.3)b,d26.2 (25.0–27.3)b31.4 (29.0–33.9)d26.5 (24.3–28.8)34.1 (29.9–38.6)d28.1 (26.4–29.8)
No. of agents
 Uncontrolled hypertensiona2.1±0.9 2.1±0.0d2.1±0.0 2.2±0.0d2.1±0.02.2±0.0c0.1±0.0
 Controlled hypertensiona2.0±0.9 2.2±0.0d 2.0±0.0d2.2±0.12.1±0.02.2±0.12.2±0.0
 With diabetese2.3±1.02.3±0.02.2±0.0 2.5±0.1b 2.1±0.1d2.3±0.12.3±0.0
 Without diabetese2.0±0.92.0±0.0 1.9±0.0b2.0±0.02.0±0.0 2.1±0.1d2.0±0.0c
No. of risk factors
 1a2.0±0.92.1±0.0 2.0±0.0d2.1±0.12.1±0.02.1±0.12.1±0.0
 2a2.2±1.02.2±0.02.1±0.02.2±0.12.1±0.12.3±0.12.2±0.0
 ≥3a2.3±1.02.3±0.02.2±0.02.3±0.12.2±0.12.3±0.12.2±0.1
No. of comorbidities
 1f2.2±0.92.4±0.0c2.3±0.0c2.4±0.1c2.3±0.12.2±0.12.3±0.0
 2f2.3±0.92.4±0.0c2.4±0.02.4±0.12.3±0.12.4±0.12.2±0.1d
 ≥3f2.6±0.92.7±0.1c2.6±0.12.7±0.1 2.3±0.1d2.9±0.22.4±0.1c

There was a trend toward more medication use with increasing numbers of risk factors and comorbidity; differences between countries were negligible, however. The only considerable difference was in Northern Europe, where there was slightly more use of medications.

Antihypertensive Drug Treatment

The majority of patients receiving antihypertensive drugs received β-blockers (47.9%), followed by angiotensin-converting enzyme (ACE) inhibitors (42.3%). β-Blocker use was particularly frequent in Northern Europe (61.7%) and the Middle East (51.5%). ACE inhibitor use was more frequent in Southern Europe (42.7%) and North (47.6%) and Latin (44.3%) America.

Frequent drug–drug combinations included any combinations with β-blockers and ACE inhibitors/angiotensin receptor blockers (ARBs). Frequent drug–drug combinations utilized either ACE inhibitors/ARBs together with thiazide diuretics or calcium channel blockers (CCBs). Differences between regions were substantial, with less frequent use of renin-angiotensin system–based combinations in Asia (Table VI).

Table VI.   Medical Treatment in Patients With Hypertension Per Drug Class, Adjusted for Age, Sex, Diabetes Mellitus, and Number of Comorbidities
 Total (N=18,652)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as percentage (95% confidence interval. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β-blocker; CCB, calcium channel blocker; CI, confidence interval; NA, not applicable.

Antihypertensive agent
 Loop diuretic9.5 (9.1–10.0)8.5 (7.8–9.3)8.2 (7.5–8.9)4.9 (4.0–5.9)4.4 (3.5–5.4)8.6 (6.4–11.4)6.4 (5.5–7.3)
 Thiazide diuretic30.8 (30.2–31.5)27.9 (26.7–29.2)30.9 (29.7–32.1)42.1 (39.5–44.8)38.2 (35.8–40.7)34.4 (30.3–38.8)25.7 (24.1–27.4)
 ACEI42.3 (41.6–43.0)45.5 (44.1–46.8)42.7 (41.5–44.0)47.6 (45.0–50.3)44.3 (41.8–46.9)31.3 (27.3–35.6)32.5 (30.7–34.3)
 ARB35.9 (35.2–36.6)29.6 (28.4–30.9)41.3 (40.0–42.5)31.2 (29.0–33.9)36.1 (33.7–38.6)47.2 (42.8–51.6)34.4 (32.6–36.2)
 BB47.9 (47.1–48.6)61.7 (60.3–63.0)39.7 (38.4–40.9)42.0 (39.4–44.7)39.3 (36.8–41.8)51.1 (46.6–55.6)47.9 (46.0–49.9)
 CCB36.0 (35.3–36.6)29.4 (28.2–30.7)32.0 (30.8–33.2)42.0 (39.4–44.6)35.4 (33.0–37.8)38.7 (34.4–43.2)55.1 (53.2–57.0)
Dual combinations of antihypertensive agent
 Thiazide diuretic + ACEI13.0 (12.6–13.5)13.2 (12.3–14.1)13.0 (12.1–13.8)17.7 (15.8–19.8)15.0 (13.3–16.9)8.9 (6.6–11.8)8.8 (7.8–10.0)
 CCB + ACEI12.8 (12.4–13.3)12.7 (11.8–13.6)11.9 (11.1–12.7)17.2 (15.3–19.2)11.7 (10.2–13.5)10.4 (8.0–13.4)12.5 (11.3–13.8)
 CCB + BB14.7 (14.2–15.2)15.9 (14.9–16.8)9.6 (8.9–10.4)16.4 (14.6–18.4)12.0 (10.5–13.8)13.9 (11.1–17.2)23.4 (21.8–25.2)
 Thiazide diuretic + ARB13.6 (13.2–14.1)11.6 (10.8–12.5)15.1 (14.2–16.0)15.5 (13.7–17.5)17.4 (15.6–19.4)20.9 (17.5–24.8)9.7 (8.6–10.9)
 CCB + ARB12.1 (11.6–12.5)8.3 (7.6–9.0)12.1 (11.2–12.9)13.3 (11.6–15.1)10.6 (9.2–12.3)14.6 (11.7–18.1)17.6 (16.1–19.1)
 Thiazide diuretic + loop diuretic0.9 (0.7–1.0)1.1 (0.9–1.5)0.5 (0.3–0.7)0.6 (0.3–1.0)0.2 (0.1–0.6)NA0.4 (0.2–0.7)
 BB + ACEI19.2 (18.6–19.8)24.3 (23.2–25.5)16.0 (15.1–17.0)17.9 (16.1–20.0)13.9 (12.2–15.8)15.2 (12.3–18.6)12.6 (11.5–13.9)
 BB + ARB14.2 (13.7–14.7)14.8 (13.9–15.8)13.0 (12.1–13.8)12.1 (10.5–13.9)12.5 (10.9–14.3)20.2 (16.9–24.0)14.8 (13.5–16.2)
 BB + thiazide diuretic13.7 (13.2–14.2)16.0 (15.0–17.0)11.1 (10.4–11.9)15.4 (13.6–17.4)15.5 (13.7–17.4)17.5 (14.3–21.2)11.5 (10.4–12.8)
 Loop diuretic + ACEI4.8 (4.5–5.1)4.6 (4.0–5.1)3.6 (3.2–4.1)2.3 (1.8–3.1)1.9 (1.3–2.6)3.5 (2.3–5.4)2.4 (2.0–3.0)
 Loop diuretic + BB5.2 (4.8–5.5)5.5 (4.9–6.1)3.3 (2.9–3.8)2.5 (1.9–3.3)2.1 (1.5–2.9)3.9 (2.6–5.9)2.8 (2.3–3.4)
 ACEI + ARB2.3 (2.1–2.5)2.3 (1.9–2.7)2.3 (1.9–2.7)3.7 (2.8–4.7)1.4 (0.9–2.1)1.3 (0.6–2.7)0.7 (0.4–1.1)
 Loop diuretic + ARB3.3 (3.1–3.6)2.8 (2.4–3.2)3.0 (2.6–3.4)1.8 (1.3–2.5)1.4 (1.0–2.1)4.0 (2.7–6.1)2.0 (1.5–2.5)

Medication Use in Patients With or Without Diabetes

The average number of drugs used in patients with diabetes was 2.3±1.0 and in those without diabetes was 2.0±0.9 (Table V). Table VII compares the use of different antihypertensive drug classes in patients with and without diabetes. Overall, all drug classes were used more frequently in patients with diabetes, except for thiazide diuretics (and ARBs); however, ACE inhibitors, loop diuretics, and CCBs were used particularly frequently in these patients.

Table VII.   Antihypertensive Drug Class Prescription in Patients With or Without Diabetes Mellitus by Region and in Total, Adjusted for Age, Sex, and Number of Comorbidities
 Total (N=18,652)Europe (North) (n=5655)Europe (South) (n=6655)North America (n=1455)Latin America (n=1560)Middle East (n=570)Asia (n=2757)
  1. Values are expressed as percentage (95% confidence interval). Abbreviations: ACE, angiotensin-converting enzyme; DM, diabetes mellitus.

Loop diuretic
 DM (−)7.9 (7.46–8.4)7.1 (6.4–8.0)7.1 (6.4–7.9)3.2 (2.4–4.2)3.7 (2.8–4.9)9.3 (6.6–13.1)5.7 (4.8–6.7)
 DM (+)14.3 (13.2–15.3)13.8 (12.1–15.6)12.9 (11.2–14.9)11.1 (8.5–14.4)7.0 (4.7–10.4)9.7 (5.9–15.5)9.2 (7.1–11.8)
Thiazide diuretic
 DM (−)30.6 (29.8–31.4)26.8 (25.4–28.3)30.6 (29.3–31.9)42.1 (39.0–45.3)38.8 (36.1–41.6)35.6 (30.7–40.9)25.8 (24.0–27.7)
 DM (+)32.0 (30.6–33.4)31.0 (28.8–33.4)31.8 (29.3–34.5)42.2 (37.5–47.1)35.3 (30.1–40.9)31.3 (24.1–39.5)25.2 (21.8–28.9)
ACE inhibitor
 DM (−)39.9 (39.1–40.7)41.7 (40.1–43.3)41.4 (40.0–42.8)43.3 (40.2–46.4)43.7 (40.9–46.6)28.9 (24.4–33.9)31.3 (29.4–33.3)
 DM (+)49.6 (47.9–50.9)56.1 (53.6–58.5)46.7 (43.9–49.5)59.1 (54.3–63.9)44.7 (39.2–50.4)39.4 (31.7–47.7)35.6 (31.8–39.6)
Angiotensin receptor blocker
 DM (−)35.4 (34.6–36.2)29.8 (28.3–31.2)40.8 (39.4–42.2)30.1 (27.3–33.0)35.8 (33.2–38.6)46.8 (41.6–52.0)32.3 (30.3–34.3)
 DM (+)37.0 (35.6–38.4)29.7 (27.5–32.1)42.6 (39.9–45.4)34.9 (30.4–39.7)36.8 (31.6–42.5)48.2 (40.1–56.4)42.0 (38.0–46.0)
β-Blocker
 DM (−)46.9 (46.0–47.7)61.7 (60.1–63.3)38.7 (37.3–40.1)41.4 (38.2–44.5)38.1 (35.3–40.9)52.5 (47.1–57.8)46.9 (44.8–49.1)
 DM (+)50.8 (49.3–52.3)61.8 (59.3–64.2)43.1 (40.3–46.0)44.3 (39.4–49.2)43.2 (37.6–49.0)48.8 (40.4–57.2)50.9 (46.7–55.0)
Calcium channel blocker
 DM (−)34.9 (34.1–35.7)28.8 (27.4–30.3)32.0 (28.7–31.3)39.7 (36.6–42.8)33.5 (30.9–36.2)36.8 (31.8–42.1)54.9 (52.8–57.0)
 DM (+)39.9 (38.4–41.3)31.8 (29.6–34.2)39.1 (36.4–41.9)48.4 (43.6–53.3)42.0 (36.5–47.7)44.3 (36.3–52.6)54.8 (50.7–58.8)

Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

The present study provides a global picture of hypertension treatment and control in cardiology practice. This is important because cardiologists often treat patients with more advanced CV disease in which an intervention is particularly effective in improving prognosis. The key findings of the present study are that: (1) BP control is at best just above 50% (Hong Kong 51.8%) globally, but in the majority of countries it is markedly lower; (2) control rates in diabetic patients are substantially worse (8.3%) than in nondiabetic patients (25.3%); (3) control rates do not substantially differ with respect to comorbid risk factors and disease; (4) about one third of patients received monotherapy, dual therapy, and triple combination therapy, respectively; and (5) frequent use of β-blockers was noted, despite the fact that only a subset of patients had compelling indications for their use and despite the recent debate on the long-term CV risk of β-blocker usage in antihypertensive treatment.15

Hypertension Control Rates

The present analysis of the global i-SEARCH study shows low BP control rates, findings that are in line with data from previous epidemiologic studies in the general population and primary care.5,6,9,16 The study further expands the knowledge on hypertension treatment and control, specifically in the clinical cardiology setting, data that are thus far only available from selected observations. Silber and colleagues17 reported a control rate of 35.3% from random office BP measurements and 27.6% from long-term BP measurements, rates that are higher than those from the present analysis, where only 11.7% (95% CI, 10.7–12.7) of patients had controlled BP. The observed differences are likely due to the fact that diabetes was not considered in the analysis when defining BP targets. Considering the lower threshold of BP for diabetic patients (<130/80 mm Hg), only 8.3% of patients had controlled BP, while 25.3% of nondiabetic patients met the BP goal of <140/90 mm Hg.

Previous publications on hypertension control have been limited to only a few countries6,9 and usually have reported data from a combined analysis of different epidemiologic studies with substantial differences in methodology.5,6,9,16 In contrast, our data provide an analysis from a global sample of patients recruited within one single study and during a short period. It confirms the high level of BP control in North America, as has been previously reported.6,9 Reasons for this difference are largely speculative; however, and it may be argued that guidelines of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)18 specifically address hypertension treatment for office-based physicians and give clear advice on how to start with antihypertensive treatment and how to proceed when control is not achieved. On the other hand, some regard the guidance of the European Society of Hypertension/European Society of Cardiology (ESH/ESC)4 to be less practice-oriented, and choice of drugs to initiate or optimize therapy are largely at the discretion of the treating physician. The present study may confirm this notion by showing that thiazide diuretic use (as recommended by JNC 7) is indeed higher in North and Latin America (42% and 38% vs 28% in Northern Europe) but also shows that monotherapy is more frequently escalated to combination therapy (73% and 70% vs 68% in Northern Europe). While the choice of drug may not be particularly important, the precise instruction on how to start and escalate therapy may be.

Hypertension Treatment: The Dominance of β-Blocker Use

Although there was a large variation in the use of different drug classes among cardiologists participating in this survey, β-blockers and renin-angiotensin system–blocking agents were frequently 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 CCBs and diuretics are first-line drugs for 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 patients with 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.19 The more surprising finding is the frequent use of β-blockers in this survey. A recent drug-utilization study investigated the use of antihypertensive drugs in 6 countries throughout Europe.20 Finnish and Swedish patients received β-blockers in 25% of cases, with a substantially lower use in Denmark (10%). Our finding might, therefore, in part, indicate an inclination of cardiologists to prescribe drugs with known CV benefits, rather than strictly following hypertension treatment guidelines.4 In comparison with other antihypertensive drugs, however, the effect of β-blockers is less optimal, with a raised risk of stroke. Hence, it has been suggested that β-blockers should not remain the first choice in the treatment of primary hypertension.21

Considerable Burden of Avoidable Complications and Costs

The average age of patients in the present study was 63 years, and patients had considerable comorbidity reflected by the presence of diabetes (24%), CAD (24%), and history of MI (31%). These patients are at considerable risk for further CV events, and hypertension is an essential component of treatment that would result in a considerable lowering of risk. In their costing report,22 NICE illustrated that lowering BP to 140/90 mm Hg would result in a 42% to 44% reduction of stroke and 33% to 35% reduction of ischemic heart disease in the age group documented in i-SEARCH. Assuming that a 9% stroke risk reduction and 4% ischemic heart disease risk reduction would be achievable by intensifying therapy (dual and triple-combination therapy instead of monotherapy), they calculated that this would result in £222 million savings for the British Health Care System.

Limitations

Despite the comprehensive and global nature of this cross-sectional survey, a few limitations of this study deserve mentioning: (1) BP measurements were obtained after at least 5 minutes of rest by sphygmomanometry or automated validated devices. It should be noted, however, that this was a naturalistic study in routine care with no monitor carrying out quality assurance and, thus, it was not feasible to quantify to what degree doctors complied with the rules. In particular, it is not possible to indicate whether doctors based their hypertension indication on one or more measurements. (2) The relation of BMI, waist circumference, and hypertension may differ across regions of the world and is quite complex.23 We, therefore, have not considered these measures to adjust our data. (3) Because to report drug utilization was only a secondary aim of our study and because it would make the data even more complex, we obtained no data on substances used (instead of drug classes), the doses used, and the dosing schedule, and on compliance (which would have required a longitudinal approach).

Conclusions

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

The present survey illustrates the potential for an improvement of BP control in daily practice. BP readings were on average too high and not tailored toward an increased risk, such as for patients with diabetes and further concomitant CV morbidity. This would result in considerable reductions of morbidity and would lead to further costs savings despite the initially higher drug costs. The global view also allows comparing country and patient characteristics with respect to hypertension treatment and control and may thus allow intensifying efforts to control BP, which have frequently been largely unsuccessful in the past.

Acknowledgments and disclosures:  The authors would like to thank Sam Zhong for statistical support provided. The study was supported by Sanofi-Aventis, Paris, France. MT and WDP are employees of the sponsors of the study. PB, MB, MV, BVK, and UT have been consulting for Sanofi-Aventis and received speaker honoraria and research support.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
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