Abstract
For patients with newly diagnosed hypertension, angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first‐line therapies. There is, however, no real‐life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL‐M) vs ACE inhibitors in real‐world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL‐M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL‐M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL‐M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors.
The European Society of Hypertension and other groups have published guidelines for the diagnosis of hypertension and recommendations for selecting the most appropriate treatment strategy.1 For patients with newly diagnosed hypertension, initiation of antihypertensive therapy with renin angiotensin system (RAS)–blocking agents has emerged as an attractive first step to control blood pressure (BP).1, 2 However, real‐life data on the relative clinical effectiveness and drug tolerability of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors are scarce. It therefore appears necessary to evaluate clinical differences between the two classes of drugs in order to identify variations in clinical effectiveness and drug tolerability.
Clinical trial data such as those from the randomized controlled study published by Bönner and colleagues3 suggest an increased efficacy of the ARB azilsartan medoxomil (AZL‐M) compared with the widely used ACE inhibitor ramipril. At a mean baseline BP of 161.1±7.9/94.9±9.0 mm Hg, there was a substantial decrease in systolic BP (SBP) with 40 mg of AZL‐M (20.6±0.95 mm Hg), while treatment with 10 mg of ramipril resulted in a mean decrease in SBP of 12.2±0.95 mm Hg (P<.001). Adverse events (AEs) leading to discontinuation were less frequent with 40 mg of AZL‐M (2.4%) than with 10 mg of ramipril (4.8%).
This led us to hypothesize that the initial decision on whether to initiate therapy with an ACE inhibitor or an ARB as a first‐line treatment for hypertension may have significant implications for the patient. For this reason we analyzed the dataset of the Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY) registry, in which approximately one third of patients had newly diagnosed hypertension at baseline for the relative effectiveness and tolerability of both classes of drug.
Methods
The EARLY registry is a prospective, observational, national, multicenter registry with a follow‐up of 12 months. Details of the study protocol have been published previously.4 The protocol was approved by the independent international ethics committee in Freiburg and the ethics committee of the State Medical Council of Rheinland Pfalz, Germany. All patients enrolled in the registry provided written informed consent.
Selection of Sites and Patients
The registry was established in primary care offices in Germany. Centers were selected from a database maintained at the Institut für Herzinfarktforschung, Ludwigshafen. The selection was made in order to achieve a representative overview of the treatment of hypertension in Germany.
Adult patients (18 years and older) with essential hypertension were included on a consecutive basis. In addition to having provided written informed consent, they also had to fulfil the following criteria: (1) either taken no antihypertensive treatment prior to inclusion or taking a non–RAS‐based antihypertensive monotherapy, and (2) monotherapy of AZL‐M or any ACE inhibitor was initiated at baseline. Patients were excluded from participation if they: (1) received antihypertensive drugs for an indication other than hypertension (eg, β‐blockers or diuretics for heart failure), (2) had a history of alcohol, drug abuse, or illegal drug addiction (expected lack of compliance with registry requirements), (3) had a life expectancy <1 year, (4) were pregnant or breast feeding, or (5) were participating in other trials or registries. In addition, patients with contraindications as to the summary of product characteristics of AZL‐M or the ACE inhibitors chosen were not included.
At the baseline visit, patients were assigned to the ACE inhibitor or AZL‐M groups with or without a continuation of the prior antihypertensive medication (no prior treatment in those with newly diagnosed hypertension) and this decision was at the physician's discretion.
Statistical Analysis
Continuous variables were summarized using descriptive statistics (absolute numbers, means plus standard deviations, or medians with 25th and 75th percentiles), as appropriate. Categorical data were described by the number and percentage of patients in each category. Comparisons between treatment groups were performed using a Pearson's chi‐square test for categorical variables or the Kruskal‐Wallis test for continuous measurements.
To assess differences in BP between groups that differ at baseline we employed two multivariate models (Table 3). Model 1 consisted of adjustment according to SBP/diastolic BP (DBP) at baseline. Model 2 considered the following: age, sex, and diabetes, in addition to model 1 (SBP/DBP at baseline). We further considered including stroke and chronic kidney disease but refrained from doing so because of the lack of a clinical impact of prior stroke and the lack of a predefined and consistent definition for chronic kidney disease. P values ≤.05 were considered significant. All P values given are the result of two‐sided tests. Statistical analysis was performed using SAS 9.2 software (SAS Institute, Inc, Cary, NC).
Table 3.
Safety of AZL‐M and ACE Inhibitors During 1 Year of Follow‐Up
| Newly Diagnosed Hypertension (n=1153) | Established Hypertension (n=1929) | P Value | AZL‐M (Newly Diagnosed) (n=789) | ACE Inhibitor (Newly Diagnosed) (n=364) | P Value | |
|---|---|---|---|---|---|---|
| Patients without an AE, % | 93.5 | 92.7 | .40 | 92.8 | 95.1 | .14 |
| Patients with an AE, % | 6.5 | 7.3 | .40 | 7.2 | 4.9 | .14 |
| Laboratory values | ||||||
| ∆ HbA1c, % | 0.00±0.87 | 0.04±0.99 | .76 | 0.04±0.91 | −0.11±0.78 | .20 |
| ∆ Fasting glucose, mg/dL | 3.34±76.62 | 2.07±19.28 | <.05 | 5.84±90.74 | −2.54±18.59 | .75 |
| ∆ Creatinine, mg/dL | 0.05±0.19 | −0.06±0.98 | .18 | 0.06±0.19 | 0.03±0.19 | .51 |
| ∆ Potassium, mmol/L | 0.02±0.48 | 0.03±0.48 | .86 | 0.01±0.45 | 0.05±0.56 | .60 |
| ∆ eGFR, mL/min/1.73‐m2 | −2.41±10.85 | −0.92±13.53 | .11 | −2.91±10.37 | −1.26±11.89 | .67 |
Abbreviations: AE, adverse event; ACE, angiotensin‐converting enzyme; AZL‐M, azilsartan medoxomil; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin.
Results
Patient Flow
Between January 2012 and February 2013, a total of 3849 patients were included in the EARLY registry (Figure), of which 1419 had newly diagnosed and 2430 established hypertension. The 12‐month follow‐up was completed by 3082 patients (1153 newly diagnosed, 1929 established hypertension). The mean age of these patients with a 12‐month follow‐up was 59.6 (±12.9) years, 48.1% were women, and the mean body weight was 83.0 (±15.6) kg (Table 1).
Figure 1.
Patient flow chart.
Table 1.
Characteristics of Patients After 12‐Month Follow‐Up
| Total (N=3082) | Newly Diagnosed Hypertension (n=1153) | Established Hypertension (n=1929) | P Value | AZL‐M (Newly Diagnosed) (n=789) | ACE Inhibitor (Newly Diagnosed) (n=364) | P Value | |
|---|---|---|---|---|---|---|---|
| Age, y | 59.6±12.9 | 56.0±12.7 | 61.7±12.6 | <.0001 | 56.3±12.2 | 55.2±13.7 | .35 |
| Women, % | 48.1 | 44.2 | 50.4 | <.001 | 45.1 | 42.3 | .37 |
| Body weight, kg | 83.0±15.6 | 83.3±15.9 | 82.8±15.4 | .46 | 83.5±16.1 | 82.9±15.5 | .85 |
| Hypertension | |||||||
| Office SBP, mm Hg | 159.3±16.9 | 161.5±15.8 | 157.9±17.3 | <.0001 | 162.5±16.0 | 159.4±15.2 | <.001 |
| Office DBP, mm Hg | 93.5±10.4 | 95.1±9.7 | 92.6±10.7 | <.0001 | 95.6±9.7 | 94.0±9.6 | <.05 |
| Mean BP, mm Hg | 115.4±10.8 | 117.3±9.8 | 114.4±11.2 | <.0001 | 117.9±10.0 | 115.8±9.4 | <.01 |
| Pulse pressure, mm Hg | 65.8±15.2 | 66.4±14.9 | 65.4±15.4 | <.01 | 66.9±14.8 | 65.4±15.0 | <.05 |
| BP <140/90 mm Hg, % | 5.9 | 2.3 | 8.0 | <.0001 | 2.5 | 1.9 | .52 |
| Hypertension grade | |||||||
| High normal | 3.9 | 1.7 | 5.2 | <.0001 | 2.2 | 1.8 | .59 |
| Grade 1 | 32.9 | 28.4 | 35.6 | <.0001 | 24.8 | 33.3 | <.001 |
| Any EOD | 63.3 | 56.1 | 66.1 | <.05 | 52.8 | 61.5 | .26 |
| No EOD | 36.7 | 43.9 | 33.9 | <.05 | 47.2 | 38.5 | .26 |
| Grade 2 | 43.1 | 48.4 | 40.0 | <.0001 | 49.3 | 45.5 | .18 |
| Grade 3 | 18.1 | 20.9 | 16.4 | <.01 | 23.2 | 19.0 | .07 |
| Elderly (65–79 y) | 31.5 | 22.1 | 37.1 | <.0001 | 22.8 | 20.6 | .40 |
| SBP 140–159 mm Hg, % | 37.1 | 36.1 | 37.5 | .69 | 31.7 | 46.7 | <.05 |
| SBP ≥160 mm Hg, % | 54.6 | 61.2 | 52.3 | <.05 | 66.1 | 49.3 | <.05 |
| Elderly (≥80 y) | 5.0 | 2.5 | 6.3 | <.0001 | 2.2 | 3.3 | .25 |
| SBP 140–159 mm Hg, % | 34.4 | 24.1 | 36.9 | .19 | 23.5 | 25.0 | .93 |
| SBP ≥160 mm Hg, % | 55.6 | 72.4 | 51.6 | <.05 | 76.5 | 66.7 | .56 |
| Comorbidity | |||||||
| Diabetes, % | 19.8 | 13.3 | 23.7 | <.0001 | 13.1 | 13.8 | .74 |
| Heart failure, % | 5.8 | 2.3 | 7.8 | <.0001 | 2.7 | 1.6 | .29 |
| CAD, % | 9.8 | 4.9 | 12.7 | <.0001 | 4.6 | 5.8 | .38 |
| Prior stroke/TIA, % | 2.5 | 1.8 | 3.0 | .05 | 1.9 | 1.6 | .77 |
| PAD, % | 3.2 | 2.2 | 3.8 | <.05 | 2.0 | 2.5 | .63 |
| COPD, % | 8.2 | 7.7 | 8.6 | .41 | 7.7 | 7.7 | .99 |
| Renal function | |||||||
| Known renal disease, % | 3.4 | 1.4 | 4.7 | <.0001 | 1.3 | 1.6 | .61 |
| Microalbuminuria, % | 6.7 | 4.3 | 7.9 | <.05 | 5.0 | 2.8 | .30 |
Abbreviations: AZL‐M, azilsartan medoxomil; BP, blood pressure; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; SD, standard deviation; TIA, transient ischemic attack. Values are indicated in percentage, median (interquartile range), or mean±standard deviation. End‐organ damage (EOD) was defined as any of the following: diabetes, heart failure, coronary artery disease (CAD), stroke, peripheral artery disease (PAD), known renal disease, microalbuminuria, or left ventricular hypertrophy.
Baseline Characteristics
As shown in Table 1, compared with patients with established hypertension, the newly diagnosed group was younger and had higher SBP, DBP, mean BP, and pulse pressure. Furthermore, greater proportions of these patients were classified as having grade 2 or 3 hypertension. There was a lower proportion of elderly (65 to 79 years) and very elderly (80 years and older) patients in the newly diagnosed group, with an SBP ≥160 mm Hg being more frequent among these patients in comparison to those with established hypertension (P<.05 for both age groups). Apart from chronic obstructive pulmonary disease, the prevalence of all comorbidities was significantly lower in patients with newly diagnosed hypertension.
Among the 1153 newly diagnosed patients who completed the 12‐month follow‐up, 789 received AZL‐M and 364 received an ACE inhibitor (Table 1). At baseline, the AZL‐M group had higher mean SBP, DBP, and pulse pressure than the ACE inhibitor group. The proportion of patients with grade 1 hypertension was lower in the AZL‐M group (24.8% vs 33.3%; P<.001). Among elderly patients, an SBP of 140 mm Hg to 159 mm Hg was more frequent in the ACE inhibitor group (46.7% vs 31.7%; P<.05), while an SBP ≥160 mm Hg was more frequent in the AZL‐M group (66.1% vs 49.3%; P<.05). All other baseline characteristics were similar between the two treatment groups.
BP‐Lowering Effectiveness
Using the raw unadjusted data, decreases at 12 months from baseline in SBP, DBP, mean BP, pulse pressure, and heart rate were numerically higher in the newly diagnosed group compared with the established group (Table 2). The proportion of patients who achieved a BP target of <140/90 mm Hg was also greater in the newly diagnosed group (62.1%) relative to the established group (58.4%; P<.05). Following adjustments for baseline SBP/DBP (model 1), and adjustments for baseline SBP/DBP, age, sex, and diabetes (model 2), decreases in SBP, mean BP, and pulse pressure, but not DBP were significantly greater in the newly diagnosed group. Using model 1, the newly diagnosed group was found to have a greater decline in heart rate, and target BP control was achieved more frequently than in the established group (62.8% vs 58.1%; P<.05). In model 2, heart rate and the percentage of target BP control were not significantly different between the newly diagnosed (61.7%) and the established group (58.9%, P=.15).
Table 2.
Blood Pressure Reductions: Comparison of Treatment Groups in Patients After 12‐Month Follow‐Up
| Newly Diagnosed Hypertension (n=1153) | Established Hypertension (n=1929) | P Value | AZL‐M (Newly Diagnosed) (n=789) | ACE Inhibitor (Newly Diagnosed) (n=364) | P Value | |
|---|---|---|---|---|---|---|
| Raw data (unadjusted), mean/% (95% CI) | ||||||
| Δ SBP, mm Hg | 28.4 (27.3–29.5) | 22.9 (22.0–23.7) | <.0001 | 29.9 (28.6–31.2) | 25.2 (23.3–27.1) | <.0001 |
| Δ DBP, mm Hg | 14.0 (13.3–14.6) | 11.7 (11.1–12.2) | <.0001 | 14.8 (14.0–15.6) | 12.1 (11.0–13.3) | <.001 |
| Δ Mean BP, mm Hg | 18.8 (18.1–19.5) | 15.4 (14.8–16.0) | <.0001 | 19.8 (19.0–20.7) | 16.5 (15.3–17.7) | <.0001 |
| Δ Pulse pressure, mm Hg | 14.4 (13.5–5.4) | 11.2 (10.5–12.0) | <.0001 | 15.1 (13.9–16.2) | 13.0 (11.3–14.7) | <.05 |
| Δ Heart rate, beats per min | 3.9 (3.2–4.5) | 2.5 (2.0–3.0) | <.001 | 4.0 (3.2–4.8) | 3.5 (2.5–4.6) | .75 |
| BP <140/90 mm Hg, % | 62.1 (59.3–65.0) | 58.4 (56.1–60.6) | <.05 | 64.8 (61.4–68.2) | 56.3 (51.1–61.5) | <.01 |
| Model 1 (adjusted), mean/% (95% CI) | ||||||
| Δ SBP, mm Hg | 26.4 (25.7–27.7) | 24.0 (23.5–24.6) | <.0001 | 29.0 (28.2–29.8) | 27.1 (25.8–28.3) | <.05 |
| Δ DBP, mm Hg | 12.6 (12.2–13.1) | 12.4 (12.1–12.8) | .58 | 14.4 (13.8–14.9) | 13.1 (12.3–13.9) | <.05 |
| Δ Mean BP, mm Hg | 17.2 (16.8–17.7) | 16.3 (16.0–16.7) | <.01 | 19.2 (18.7–19.8) | 17.8 (17.0–18.6) | <.01 |
| Δ Pulse pressure, mm Hg | 13.8 (13.2–14.5) | 11.6 (11.1–12.1) | <.0001 | 14.6 (13.9–15.4) | 13.9 (12.8–15.1) | .31 |
| Δ Heart rate, beats per min | 3.4 (2.9–3.8) | 2.8 (2.4–3.1) | <.05 | 3.8 (3.3–4.4) | 4.1 (3.2–4.9) | .61 |
| BP <140/90 mm Hg, % | 62.8 (60.0–65.6) | 58.1 (55.9–60.3) | <.05 | 65.0 (61.6–68.2) | 56.0 (50.8–61.0) | <.01 |
| Model 2 (adjusted), mean/% (95% CI) | ||||||
| Δ SBP, mm Hg | 26.0 (25.2–26.7) | 24.3 (23.8–24.9) | <.001 | 29.0 (28.2–29.8) | 27.0 (25.8–28.2) | <.01 |
| Δ DBP, mm Hg | 12.6 (12.2–13.1) | 12.5 (12.1–12.8) | .56 | 14.3 (13.8–14.9) | 13.1 (12.3–13.9) | <.05 |
| Δ Mean BP, mm Hg | 17.1 (16.6–17.6) | 16.4 (16.0–16.8) | <.05 | 19.2 (18.7–19.8) | 17.7 (16.9–18.5) | <.01 |
| Δ Pulse pressure, mm Hg | 13.3 (12.7–14.0) | 11.9 (11.4–12.4) | <.001 | 14.7 (13.9–15.4) | 13.9 (12.8–15.0) | .25 |
| Δ Heart rate, beats per min | 3.4 (2.7–4.0) | 2.8 (2.3–3.3) | .14 | 3.8 (3.3–4.4) | 4.0 (3.2–4.8) | .66 |
| BP <140/90 mm Hg, % | 61.7 (58.8–64.6) | 58.9 (56.7–61.2) | .15 | 65.1 (61.7–68.4) | 56.0 (50.8–61.1) | <.01 |
Abbreviations: ACE, angiotensin‐converting enzyme; AZL‐M, azilsartan medoxomil; CI, confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure. To illustrate the adjusted changes in blood pressure (BP), three pretreatment BP values were chosen representing the three borders between four quartiles; model 1: adjusted for SBP/DBP at baseline; model 2: adjusted for SBP/DBP at baseline (model 1), age, sex, and diabetes.
Among patients with newly diagnosed hypertension, the raw unadjusted data demonstrated that decreases from baseline at 12 months in SBP, DBP, mean BP, and pulse pressure were significantly greater in the AZL‐M group compared with the ACE inhibitor group (Table 2). In addition, attainment of target BP levels was more frequent in the AZL‐M group (64.8% vs 56.3%; P<.01). Using models 1 and 2, reductions in SBP, DBP, and mean BP were still more pronounced in the AZL‐M group. The proportion of patients with target BP levels was also significantly greater in the AZL‐M group analyzed using model 1 (65.0% vs 56.0%; P<.01) and model 2 (65.1% vs 56.0%; P<.01). Thus, treatment with the ARB AZL‐M was more effective than that with ACE inhibitors.
Safety of Antihypertension Drug Treatment During 12‐Month Follow‐Up
Adverse events (AEs) that occurred in the first year after baseline evaluation were recorded. AEs were documented in 6.5% of patients with newly diagnosed hypertension (n=1153) and 7.3% of patients with established hypertension (n=1 929; P=.40) (Table 3). Overall, 0.3% of patients with newly diagnosed hypertension died (0.4% in the established hypertension group) while none experienced stroke (0.1% for established hypertension). Among those with newly diagnosed hypertension, the proportion of patients treated with AZL‐M and ACE inhibitors experiencing an AE during 1 year were comparable (7.2% and 4.9%, respectively, P=.14). In patients with newly diagnosed hypertension, 0.5% died in the AZL‐M group and none in the ACE inhibitor group (no strokes in either group).
Laboratory testing revealed that changes in glycated hemoglobin, creatinine, potassium, and estimated glomerular filtration rate during the follow‐up were not significantly different between groups (Table 3). Fasting glucose level increased slightly more in the newly diagnosed group (P<.05); however, the variability of the data was extremely high. There were also no significant differences in laboratory values between the AZL‐M and ACE inhibitor treatment groups in patients with newly diagnosed hypertension.
Discussion
The present study explored the clinical characteristics between patients with newly diagnosed vs established hypertension and compared the efficacy and safety of the ARB AZL‐M with the efficacy and safety of ACE inhibitors. The newly diagnosed patient group was younger and had higher BP values. Following 12 months of antihypertensive treatment, these patients displayed greater reductions from baseline in SBP, mean BP, and pulse pressure compared with patients with established hypertension.
Despite the availability of effective and safe antihypertensive drugs, at least 40% of hypertensive patients continue to experience unacceptably high BP.5 Poor adherence to treatment strategies has been suggested as a main contributor for uncontrolled hypertension. Indeed, it has been reported that only 25% of patients with newly initiated treatment redeem their first prescription, and among those who do, the rate of discontinuation during the first year is approximately 50%.6, 7, 8 Selection of the optimal first‐line antihypertensive regimen with respect to efficacy and tolerability is known to positively influence both treatment compliance and persistence.1, 9, 10 Several studies suggest that targeting the RAS with ACE inhibitors or ARBs is associated with the greatest antihypertensive therapy persistence.6, 10, 11, 12 In the present study, a similar proportion of newly diagnosed patients and those with established hypertension persisted with the initially prescribed therapy during the 12‐month follow‐up.
Data obtained for the newly diagnosed patients who were assigned to AZL‐M or an ACE inhibitor at baseline demonstrate that treatment persistence up to the 12‐month follow‐up was similar for the groups. The proportion of newly diagnosed patients who achieved target BP control was 9% higher in the AZL‐M group compared with the ACE inhibitor group. This finding is consistent with a retrospective assessment of real‐life data by Petrella and colleagues12 where after 9 months of treatment with newly initiated monotherapy, BP targets were met by 28% and 27% of patients receiving ARBs and ACE inhibitors, respectively. Interestingly, the same report stated that ARB‐based dual therapy resulted in a significantly higher rate of BP control compared with non–ARB‐based dual therapy; however, it should be noted that AZL‐M was not available at the time the study was conducted. A more recent meta‐analysis of randomized controlled trials by Takagi and colleagues13 concluded that AZL‐M reduced BP more substantially than other antihypertensive therapies, consistent with the findings of the present registry.
In terms of safety, the incidence of AEs was low, with the newly diagnosed patients experiencing similar incidences of events to the patients with established hypertension. There was also little difference in the incidence of AEs between the groups. AEs were tracked more closely in the AZL‐M arm, however, giving rise to the speculation that rates in the ACE inhibitor arm may actually be higher than those reported. Hospitalization for hypertension or related complications was also comparable and very low for both drugs (data not shown). This is in agreement with previous studies that have demonstrated low incidences of moderate to severe adverse events experienced by patients being treated with either AZL‐M or ACE inhibitors.14, 15, 16 The results of laboratory testing further demonstrated the safety of the two drugs, with no significant changes in levels of the components tested over the 12‐month follow‐up period.
Limitations
There were a number of limitations to the present registry. Firstly, owing to the inherent characteristics of an observational study, treatment allocation was not randomized and thus patient characteristics and BP values at baseline were not comparable. This resulted in an imbalance in patient number between the two groups, although the sizes of both were high overall. Furthermore, ramipril was the most commonly prescribed ACE inhibitor, and while a limited number of other agents were allowed, the numbers of patients were not high enough to draw comparisons between them. Another limitation is that the medication regimen was left to the discretion of the treating physician, which may have resulted in patients with certain characteristics being preferentially prescribed one class of drug over the other. This would likely introduce a level of bias to the data. Finally, the incidence of AEs was extremely low in both patient groups, making it difficult to satisfactorily determine differences between the two classes of drug. Further, AEs might have been tracked more closely in the AZL‐M arm, giving rise to the speculation that rates in the ACE inhibitor arm are actually higher than reported. AZL‐M was monitored very close because AZL‐M was newly available at the time of this observation. For this reason, there might have been a higher vigilance as to any AEs associated with AZL‐M. On the other hand, the ACE inhibitor group received very established treatments with a well‐described side effect profile. It might be expected that physicians were not as vigilant to the side effects caused by ACE inhibitors than by AZL‐M.
Implications for Clinical Practice
Patients with newly diagnosed hypertension display distinct patient characteristics and a lower comorbidity burden compared with patients with long‐standing hypertension. Prior guidance from the British Society of Hypertension, for example, has suggested different treatment strategies in young and older patients. In essence, there is a long‐standing debate on which drug class should be considered first‐line treatment in the control of hypertension. Prior evidence has pointed at a high rate of β‐blocker and diuretic drug treatment use in patients with newly diagnosed hypertension,17 although inhibitors of the RAS are considered to be effective while also being highly tolerable. Current guidelines usually refrain from recommending individual drug classes or even particular drugs unless there are further major conditions requiring the preferred use of one over another.18, 19, 20, 21 In many cases there is no difference made between the use of ACE inhibitors or ARBs. Our results suggest that using a highly effective but tolerable drug even from within the different drug classes of renin angiotensin–blocking agents may translate into clinical benefit.
Conclusions
This study demonstrates that AZL‐M, when compared with ACE inhibitors, provided superior BP control for patients with newly diagnosed hypertension, with a similar safety profile. Following newly initiated treatment with AZL‐M or an ACE inhibitor, BP targets were met by a similar proportion of patients with newly diagnosed and established hypertension.
Statement of Financial Disclosure
AKG, PBra, SAP, PBau, FM, JS, and RES have received research support and/or honoraria for lectures from a number of pharmaceutical companies producing antihypertensive drugs, including Takeda, the sponsor of this study. TO is an employee of the Institut für Herzinfarktforschung, Ludwigshafen, Germany, the CRO responsible for the conduct of this study. HB is a freelance consultant for Takeda. ME is an employee of Takeda Pharma Vertrieb GmbH & Co KG.
Author Contributions
AKG, PBra, SAP, PBau, FM, JS, and RES designed the registry. TO was responsible for the analysis of data. HB and ME were responsible for the project management from the sponsor's side. AKG and PBra drafted the manuscript, and all authors revised the article for important intellectual content. All authors have approved the final version.
Author Information
EARLY Registry Group: Anselm K. Gitt (Co‐Chair, Ludwigshafen), Peter Baumgart (Münster), Peter Bramlage (Mahlow), Martina Ehmen (Berlin), Felix Mahfoud (Homburg/Saar), Sebastian A. Potthoff (Düsseldorf), Steffen Schneider (Ludwigshafen), Hartmut Buhck (Hannover), Roland E. Schmieder (Chair, Erlangen), Jochen Senges (Ludwigshafen), Georg Lübben (previously Takeda), Claus Jünger (Ludwigshafen), Alexander Neumer (Ludwigshafen), Karin Vonderschmitt (Ludwigshafen), and Reinhold Hübner (Berlin).
Funding
Takeda Pharma, Berlin, Germany, funded this registry. It also provided financial support to the Institute for Pharmacology and Preventive Medicine in the preparation of this manuscript.
Acknowledgments
The authors acknowledge the substantial contribution of Dr Arne Botta and Dr Kerstin Neumann, both previous employees of Takeda, for their input into the design and setup of the registry. Furthermore, we are indebted to all the investigators across Germany who have made this registry possible.
J Clin Hypertens (Greenwich). 2015;17:947–953. DOI: 10.1111/jch.12603. © 2015 Wiley Periodicals, Inc.
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