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American Journal of Hypertension Advance Access published May 24, 2016

Original Article

Comparative Study of the Efficacy of Olmesartan/
Amlodipine vs. Perindopril/Amlodipine in Peripheral and
Central Blood Pressure Parameters After Missed Dose in
Type 2 Diabetes
Josep Redon1,2 and Gernot Pichler1 on behalf of the Missed Dose Study Group

BACKGROUND RESULTS
Central aortic blood pressure (CBP) and CBP-derived parameters are The OLM/AML combination reached the noninferiority criteria in reduc-

Downloaded from http://ajh.oxfordjournals.org/ at University of Otago on June 3, 2016
independent predictors of cardiovascular risk. Angiotensin II recep- ing central systolic BP after 24 weeks of treatment and after the missed
tor blockers (ARBs) or angiotensin-converting enzyme inhibitors plus dose, compared to the PER/AML combination (−17 and −8 mm Hg,
calcium channel blockers are the recommended first-line treatments respectively). Peripheral BP, AIx, and PWV were significantly lower in
in hypertensive diabetic patients; however, the effect in reducing CBP both groups after 24 weeks of treatment and 48 hours after the missed
when a dose is skipped has not been established yet. The aim was to dose, observing a trend to a greater reduction in CBP-derived param-
determine whether the fixed-dose combination of olmesartan/amlodi- eters in the OLM/AML group.
pine (OLM/AML) provides equal efficacy and safety as the perindopril/
AML (PER/AML) combination in reducing CBP, augmentation index CONCLUSIONS
(AIx), and pulse wave velocity (PWV) when a drug dose is missed. The OLM/AML combination is safe, well tolerated, and not inferior to
the combination of PER/AML in lowering CBP and CBP-derived param-
METHODS eters in diabetic patients. OLM/AML provides longer-lasting efficacy in
In this noninferiority, randomized, double-blind, double-dummy par- terms of CBP reduction compared to PER/AML.
allel group, controlled design trial, 88 patients received either OLM
20–40 mg/AML 5–10 mg (41 patients) or PER 4–8 mg/AML 5–10 mg Keywords: cardiovascular risk; central blood pressure; diabetes; fixed-
(47 patients) for 24 weeks. The main endpoint was the aortic sys- dose combination; hypertension; missed dose.
tolic BP (SBP) after 24 weeks of treatment at 48 hours from the last
administration. doi:10.1093/ajh/hpw033

The noninvasive assessment of central (aortic) blood pres- followed by a reduction in cardiovascular risk as reported in
sure (CBP) is gaining importance in the evaluation of car- a selected population.7 Even though antihypertensive treat-
diovascular risk.1 CBP represents the real pressure burden ment strategy in clinical practice is based on PBP values, the
exerted on the brain, the heart, and the kidneys, and CBP- assessment of CBP parameters is a validated tool in cardio-
derived parameters provide an insight into stroke volume, vascular risk stratification and can help to refine antihyper-
arterial stiffness, and the reflecting backward wave, whereas tensive treatment, especially in the high-risk population.
peripheral (brachial) BP (PBP) is mainly determined by the Among those patients with high cardiovascular risk, dia-
elasticity of the arterial vessel wall and the vessel caliber on betes mellitus (DM) is particularly relevant. DM is a major
measurement site.2 Various validated techniques for nonin- risk factor for chronic kidney disease due to macro- and
vasive assessment of CBP are available nowadays, resulting microvascular alterations of the arterial vessel wall. Diabetic
in a growing number of evidence focused on the relation- patients have higher levels of CBP, PWV, and AIx as well as
ship among hypertension, CBP, and cardiovascular risk.3–5 lower PP amplification compared to nondiabetic controls
Central systolic BP (CSBP), pulse pressure (PP) amplifica- and frequently require combinations of antihypertensive
tion, pulse wave velocity (PWV), and augmentation index drugs in order to reach BP targets.8
(AIx) are parameters, which are considered as predictors According to the ESH-ESC guidelines of 2013, the treat-
of cardiovascular morbidity and mortality, under intense ment of patients with DM should include drugs active on
research.6 Moreover, a reduction in CSBP or PWV is the renin–angiotensin–aldosterone system.9 Angiotensin II

1Hypertension Clinic, Department of Internal Medicine, Clinical Hospital
Correspondence: Josep Redon (josep.redon@uv.es).
of Valencia, INCLIVA, University of Valencia, Valencia, Spain; 2CIBERObn,
Initially submitted January 27, 2016; date of first revision February 11, Instituto de Salud Carlos III, Madrid, Spain.
2016; accepted for publication March 14, 2016.
© American Journal of Hypertension, Ltd 2016. All rights reserved.
For Permissions, please email: journals.permissions@oup.com

American Journal of Hypertension  1

in patients with valid (in all visits) CBP parameter evaluation which the effect on office BP was the criteria used to assess were included. before randomization. con. 5 mg once a day. 40 mg + AML 10 mg once a day or PER 8 mg + AML 10 mg hypertensive effect beyond 24 hours of the given drug might once a day. the anti. AIx. 5. the dose of drug treatment was However. and 6b. and AIx were also assessed. in a substudy of the “Comparative Subjects aged 40–70 years.Redon and Pichler receptor blockers (ARBs) or angiotensin-converting enzyme AML 5 mg once a day.  Study design. 8 mg + AML 5 mg once a day. and compliance check were Figure 1. patients received 1 dose partially compensate the missing dose. Supplementary Figure  1). Females of childbearing potential had to Design use adequate contraceptive methods and to have a negative The study was a post hoc analysis of a noninferiority. up-titrated to OLM 40 mg + AML 5 mg once a day or PER bination reduces the total number of drugs and. During this period.16 Eligible patients started a 1 or 2 Ethics Committee including patients. recording of concomitant medications and adverse events. of placebo single-blind treatment. At visit 2. tion of OLM 20 mg + AML 5 mg once a day or PER 4 mg + collection of unused drugs. physical examination. Protocol was approved by the Institutional the therapeutic strategy. improves patients’ adherence to treatment. During the visits. excluding com- tes” (EUDRA-CT No. Written informed con- weeks (V1) run-in period. In this post hoc analysis. in open-label conditions. double-blind. In subjects never treated or Downloaded from http://ajh. The exclusion criteria are shown in domized. In patients not normalized quence. PP amplifica- of the fixed-drug combination OLM 20–40 mg/amlodipine tion. 6a. patients matching inclusion Methods criteria were randomized to the first 12 weeks of randomized double-blind double-dummy treatment. ran. and PWV were assessed and calculated. taking 1 or 2 antihypertensive medications. during which they were treated sent prior to enrolment was required. double-dummy parallel group. The changes in PP binations with test drugs. 2016 AML in PBP and CBP after missed dose in type 2 diabe.5%. BP measurement.oxfordjournals. PWV. patients received either a combina. and in the visits 4. frequently skip to take treatment doses with a consecutive the dose of drug treatment was further up-titrated to OLM fail in treatment goals. at randomiza- The objective of the present study was to compare the effect tion.15 When a dose is skipped. At the end of the run-in period (V2). After 12 weeks (V4) of inhibitors plus calcium channel blockers have shown to combination treatment in patients not normalized by treat- reduce CBP. At 24-week visit (V6a). sitting office SBP values between amplification. In addition. 140 and 179 mm Hg and office diastolic BP values between 90 and 109 mm Hg were requested. diabetic patients had to be treated for diabetes with diet or oral SUBJECTS AND METHODS glucose-lowering drugs reaching an HbA1c ≤7.10–14 ment after 12 or 18 weeks.: 2010-018774-2). at 24 and 48 hours after the last active drug intake (missed dose). with AML. even though the introduction of a fixed-drug com. PER/ and hypertension were enrolled. with type 2 DM study of the efficacy of olmesartan (OLM)/AML vs. as a conse. patients after an additional 6 weeks of treatment at week 18 (V5). 2  American Journal of Hypertension . visit 3 (V3) and 4 (V4). (AML) 5–10 mg compared to the perindopril (PER) 4–8 mg/ AML 5–10 mg combination in reducing aortic BP after 24 Study population weeks of treatment.org/ at University of Otago on June 3. Supplementary Table S1. both in monotherapy and in combination. aortic BP. urine pregnancy test. of both sexes. in a 1:1 ratio. only the trolled design trial (Figure  1.

There were no significant differences between the 2 treat- urements of PBP recorded. On average. in peripheral. adjustments for coun- ment.8 in OLM/AML and PER/AML zation). and patients The patient population recruited in this study consisted were instructed to avoid large meals. PBP values at baseline. after 24 weeks of treatment. General characteristics of the study population are reported Radial artery applanation tonometry was used to assess in Table 1. AIx. Waveforms were processed with dedicated inhibitors or AT1 antagonists. and treatment by visit interaction and base- administration (missed dose) (baseline minus V6b). Mean line measurement (Supplementary Figure  2). General characteristics of the study population CBP and pulse wave analysis. Millar recorded in the enrolled patients. after missed-dose technique. Australia). 5. BP had to be measured in the RESULTS same arm at each visit. caffeine. Applanation patients had a long-lasting history of hypertension (duration tonometry measurements were obtained at visit 2 (randomi. patients in the PER/AML group. heart rate were measured at brachial artery level or upper The sample size for the full trial16 was calculated consider- arm. on angiotensin-converting enzyme 5-minutes sitting. forms were subjected to further analysis by the SphygmoCor software to identify the time to the peak/shoulder of the first PBP and CBP (T1) and second pressure wave components (T2) during systole. aortic BP. AtCor Medical. or study physicians. Fisher’s exact test the 2 treatment’s arms. The standing BP trial achieved statistical significance.7 and 111. treatment effect along 24 weeks). In this substudy on CBP parameters. myocar- Arterial pressure waveforms of the same arm were sampled dial infarction.org/ at University of Otago on June 3. in OLM/AML-treated patients and in American Journal of Hypertension  3 . the patient was randomized to one of mixed model for repeated measurements. to have 80% of the statistical power in a 0. and 6 (or early withdrawal). Instruments) and calibrated to the average of the last 2 meas. respectively. and no previous cardiovascular event. respectively) of both sexes. were applied. even after adjusting for fication. Chronic kidney disease was present applanation tonometry measurements were obtained by in 10. One hundred patients in each treatment group were required trally evaluated and approved by AtCor Medical (Itasca. in triplicate at 2-minute intervals by an automated elec. after 24 aged radial artery waveform and to derive a corresponding and 48 hours. and AIx using a commercially available system similar median BMI in both treatment groups. and Figure 2b for PP. smoking.oxfordjournals. the patient was kept in an upright position for 1 study. 4. IL). Office BP and patients who took at least 1 dose of the study medication. If eligible.  The assessment of CBP. The safety set included all the randomized eters were assessed by applanation tonometry.2%) and with a broad range of minimum interval of 3 minutes to examine hemodynamic ages (40–71 years). 2016 triplicate).301. in months: 102. technicians. the patients were overweight with a CBP. AML one. are shown in Table 2. and AIx was performed in a quiet room. Waveforms were then processed ment groups at study entry in the number and/or kind of with dedicated software (SphygmoCor version 7. and was given the first dose of double-blind treat. dated generalized transfer function. AtCor) and were cen. visit. at 48 hours from the last country. 24 ± 2 hours (V6a) and 48 ± 2 hours (V6b) after the last drug the number of subjects with available data on CBP param- intake. PBP was recorded using the OMRON M6 device with a with a prevalence of males (60. change during the study is shown in Figure 2a for systolic .025 one-sided Office and aortic BP measurements were performed 24 ± 2 t-test. after sitting BP measurement (in eters was around half of the power calculation for the overall Downloaded from http://ajh.007. with a superiority for SBP in the OLM/AML one. glucose-lowering and antihypertensive drugs (see Table 1).8% of the PER/ trained research nurses. stroke. overall. For each patient. visit. Office BP assessment was performed in accordance try. PWV. however. Efficacy in CBP of Olmesartan/Amlodipine in Missed Dose performed. The profile of aortic BP central aortic pressure waveform using a previously vali.6% of the OLM/AML group and in 9. 24 weeks of treatment after 24 and 48 hours from the last drug administration are shown in Statistical methods Table 2. or peripheral artery occlusion were over 10 seconds with a Millar tonometer (SPC. Aortic pressure wave. ment groups. and of 88 patients (41 patients in the OLM/AML group and 47 vasoactive drugs for 3 hours preceding the measurement. AML group. was used to compare categorical variables between treat- cation. respectively). The aortic changes from baseline were analyzed using a maximum SBP after 24 weeks (V6a) vs. All radial artery groups. Concerning aor- The statistical analyses were aimed to assess if there were tic BP. baseline was −20 and −13 mm likelihood–based repeated measures approach longitudinal Hg. Most of the (SphygmoCor. AtCor). based on the tronic digital sphygmomanometer (Omron 705CP). steadiness. when it had to be measured at baseline of −4 mm Hg. Baseline BP values as well as at week 24 of treatment. measurement was assessed again after 4 minutes from the previous one. the comparison between the 2 arms of the minute and then standing BP was assessed. The integral system software was used to calculate an aver. to reject the null hypothesis with a lower margin of hours after the last drug dose intake at each visit. was dispensed with the study medi. aortic BP and its derived param. ing data from other antihypertensive studies. PWV. PWV. the CSBP reduction over time showed a sta- differences between the OLM/AML treatment and the PER/ tistically significant trend in favor of OLM/AML (P = 0. In all the comparisons. except at acceptance for the difference reference test in changes from visit 6 (or early withdrawal). and similar median age in both groups. treatment by visit interaction and baseline measure with ESH-ESC guidelines. PBP was reduced significantly in both arms.17–19 software (SphygmoCor version 7. and PP ampli. For safety purposes. alone or in combination.

051). mg/dl 118 (31) 121 (34) 0.631 Height. cm 168. HDL. respectively (P = 0. AIx reduction over time showed a statistically OLM/AML-treated patients and in PER/AML-treated ones significant difference in favor of OLM/AML (P  =  0.876 Waist circumference. mg/dl 195 (38) 200 (41) 0. Overall. respectively.01 (P  =  0.7 (14. between treatment). and treatment by visit interaction and baseline meas.  General characteristics of the study population Olmesartan/ Perindopril/ amlodipine amlodipine P value Subjects.0 (9. n (%) 27 (65.385 Weight. PER/AML-treated ones (P  =  0.746 Male/female.1) 0. mg/dl 47 (13) 53 (17) 0. baseline was −7 and −2 mm PP amplification Hg.8 (3. visit.oxfordjournals.911 Total cholesterol. months 102.9 and patients and in the PER/AML-treated ones.4 (0.8 (9. in OLM/AML-treated patients and in PER/ AML treatment (P = 0.623 HDL cholesterol. respectively (P = 0. patients and in PER/AML-treated ones after 24 weeks of ment groups—12 and −7 mm Hg.713 Creatinine.3) 29. in OLM/AML-treated patients and in PER/ AML-treated ones (P  =  0. mg/dl 148 (85) 128 (61) 0. mg/dl 0.9) 32 (68. in OLM/AML-treated 4  American Journal of Hypertension . The central PP change at V6a vs.287 Uric acid.221 Data are mean (SD).071) and after 48 hours −5 and The PP amplification change at V6a vs.699 Hypertension treatment. Abbreviations: bpm.5 mm Hg (P = 0.0 (9.2 and +1.org/ at University of Otago on June 3.1) 8 (17. respectively.1 (7.012). in OLM/AML-treated 48 hours a significant difference appeared among the treat.3 (12.076).154). AIx and PWV After 48 hours from the missed dose.2%. between treatment).175).1) 26 (55.392 Heart rate.986 Downloaded from http://ajh. BP reduction over time showed a trend in favor of OLM/ respectively.2) 51. the CSBP change at V6b vs. n 41 47 Age. n (%) 1. mg/dl 119 (29) 120 (27) 0.05 −1 mm Hg.0) 0. (P = 0.630 Office systolic blood pressure.19) 0.1) Fasting glucose.0)   Treated but not normalized 34 (82. respectively.065 Triglycerides.049. although after −0. respectively.870 Office diastolic blood pressure.9 (38. After 48 hours of the last dose.5 and +0.5) 0. mm Hg 96 (4) 97 (5) 0. low-density lipoprotein.2 mm Hg.6) 0.0815). the aortic diastolic The AIx change at V6a vs.89 (117.000  Diet 14 (34. high-density lipoprotein. the aortic PP −0. AML-treated ones and after 48 hours −3.7) 0.3 (0.023). n (%) 1. even after adjusting for country.94 (1.9)   Hypoglycemic drug 27 (65.9) 39 (83. in Overall.2 mm Hg. bpm 78 (13) 78 (13) 0. with the described changes. kg 84.568 LDL cholesterol.7 (98.3) 58.034. mm Hg 157 (10) 158 (11) 0.Redon and Pichler Table 1. close to the statistical significance (P  =  0.0) Diabetes mellitus 2 duration.8) 102. in the OLM/AML-treated OLM/AML ( P value = 0. ure.7 (8.6% and −1.880 HbA1c % 6.83 (0. beats per minute.6) 166.16) 0. with a reduction of −0.531 Body mass index. mg/dl 5.037).9)/14 (34. The aortic diastolic BP change at V6a vs.7 (3.5) 0.87 (0.90 (1.9 (54. years 58. 2016 Hypertension duration. baseline was −17 and −8 mm Hg.7) 0. and +0. the change was Consequently.8) 0. baseline was +0. baseline was PWV reduction over time showed a trend in favor of −13 and −11 mm Hg.000   Never treated 7 (17.52) 0.7) 6.1) 15 (31.2 (10. respectively.5) 111.45) 5. reduction over time showed a trend in favor of OLM/AML treatment. kg/m2 29. respectively.496 Control of diabetes mellitus 2. cm 101. months 44.9) 0. LDL.3)/21 (44. baseline was −3. respectively.0) 83. treatment.

6 (12. PP.30 (0.051 0.86) 9.95 (1.987 0.171 0.019   OLM/AML 61 (10) 55 (9) 54 (9) 53 (10) 54 (9)   PER/AML 60 (11) 58 (12) 56 (11) 57 (13) 58 (15) Downloaded from http://ajh.002 0.bP value at student t-test comparing BP reductions.27 (0.181 0.7) 29. beats per minute.31 (0. furthermore.68) PP amplification 0.2) 25. mm Hg 0. PER.28 (1.1) PWV (m/sec) 0.05 (1. diastolic blood pressure. mm Hg 0.0) 30. Moreover.806 0.037   OLM/AML 30.17) 1.76 (1.26 (0. SBP.2 (12.008 0.9 (12.18) 1. while it was +0.0) 31. and treatment by visit interaction and base.54) 8.47) 8.013 0.5) 25.17) 1.28 (0. the American Journal of Hypertension  5 .31 (0. pulse pressure. perindopril.26 (0.78) 8.11) 8.17) 1. respectively (P = 0. and treatment by visit interaction and baseline measure.13) Data are mean (SD).024). PER/AML was reported in the estimated hours after the last administration.org/ at University of Otago on June 3.9 (11.012 0. blood pessure.346 0.17) 1.512   OLM/AML 74 (11) 75 (11) 74 (11) 74 (11) 73 (11)   PER/AML 75 (12) 75 (13) 74 (11) 75 (12) 73 (12) Aortic BP   SBP. after 24 weeks of treatment and at 48 treatment effect vs. and CSBP was statistically significant in favor of the OLM/ AML combination compared to PER/AML. olmesartan.146   OLM/AML 8. pulse wave velocity.19) 1. mm Hg 0. Abbreviations: AIx. visit.17) 1. AML.154 0. HR. heart rate.56 (1.19)  PER/AML 1.03) 8.8) 29.007 0.53)  PER/AML 9.015 0. a trend in favor of OLM/AML AML and PER/AML.059   OLM/AML 96 (5) 84 (10) 84 (9) 81 (8) 83 (9)   PER/AML 95 (4) 89 (8) 85 (10) 83 (9) 85 (10)   PP. augmentation index.3 (11. both PBP and CBP were significantly and country.04 DISCUSSION and −0.005   OLM/AML 157 (10) 139 (12) 138 (13) 135 (13) 137 (14)   PER/AML 155 (11) 147 (15) 141 (15) 140 (15) 143 (17)   DBP. Treatment effect on PBP difference. PP amplification over the time showed a statistically significant difference in In the present study conducted in hypertensive and dia- favor of OLM/AML (P  = 0. Overall.87 (2.0) 29.175 0.062 0. mmHg 0. OLM.28 (1.36) 8. visit.40 (2.08).17) 1. 2016   HR.25 (11.92) 9.023   OLM/AML 96 (7) 86 (11) 85 (9) 82 (9) 84 (9)   PER/AML 96 (5) 90 (8) 87 (8) 84 (8) 89 (9)   PP. even after adjustment for betic patients. aP value for treatment effect after adjustment for country.26 (0.080   OLM/AML 1.oxfordjournals. BP.99 (1.5) 26. with respect to baseline. systolic blood pressure.02. amlodipine. bpm 0.2 (11. DBP.  Baseline blood pressure levels Baseline (visit 2) Visit 4 Visit 5 Visit 6a Visit 6b P overalla P visit 6ab P visit 6bb Office BP   SBP. OLM/ line measure.31 (0.076 0.0 (11. PWV.024 0.29 (0. bpm. mm Hg 0.6 (12.034   OLM/AML 144 (10) 129 (14) 128 (12) 123 (13) 126 (14)   PER/AML 143 (12) 137 (14) 132 (18) 130 (16) 135 (19)   DBP.<?> Efficacy in CBP of Olmesartan/Amlodipine in Missed Dose Table 2. mm Hg 0.071 0. patients and in PER/AML-treated ones.226   OLM/AML 48 (10) 43 (11) 43 (8) 41 (10) 42 (10)   PER/AML 47 (12) 47 (12) 46 (16) 46 (15) 46 (18) AIx (%) 0.2)  PER/AML 28. consistently reduced by both treatment combinations..66 (1. in the 2 treatments.049 0.0815 0.9 (10.

) Abbreviations: AML. Overall the CSBP reduction over time showed a statistically significant trend in favor of OLM/AML (P = 0. patients with metabolic abnormalities. However. and reference values for treatment. Reduction over time showed a trend in favor of OLM/AML treatment close to statistical significance (P = 0. PP. and the level of adherence to experi. BP. and treatment by visit interaction and baseline measure. There were no sig. notoriously a group in which alterations of angiotensin-converting enzyme inhibitor/calcium chan- the large vessel function are expected. amlodipine. visit. those in which CBP parameters were assessed. indicating a possible The importance of CBP in the development of organ dam.21 hypertensive drugs has been proposed in order to improve Antihypertensive treatment lowers PBP and cardiovascular adherence. one of the major challenges for long-term anti- risk. study.26 The outcome in favor of the present study. (See text. 2016 Figure 2. blocker/thiazide combination. regimen was superior to the PER-based regimen in reduc- tical significance.007.Redon and Pichler Downloaded from http://ajh. however. ing CBP as well as 24-hour BP values. olmesartan.  (a) CSBP mean and 95% CI at baseline and during the study visits. ARB. were included in the major cardiovascular events.22–24 Drugs with vasodilatory capacity the patient unprotected.oxfordjournals. the OLM/AML compared to PER/AML. allowing for comparison In accordance with previous results. However.33 The OLM-based drug comparison between the 2 arms of the trial achieved statis. perindopril. reduction in AIx showed a significant difference in favor of such as angiotensin-converting enzyme inhibitor.27–32 both OLM/ between the 2 experimental groups. dose with the 2 components is skipped. nel blocker combination in that study may be explained by nificant differences in clinical characteristics between the 2 the greater effect on CBP reduction compared to the beta groups at study entry.25 In the ASCOT-BPLA and PP amplification increment. while a trend in favor of the calcium channel blocker have a greater impact on CBP than OLM/AML combination was observed in PWV reduction beta blockers or thiazide diuretics.051). mental treatment was very high. it is relevant to know what 6  American Journal of Hypertension . blood pressure. OLM. (b) Central PP mean and 95% CI at baseline and during the study visits. pulse pressure. some concern exists if a agement of hypertension lower CBP with the same magni. even after adjustment for country. the superiority of CBP over the PBP values in terms of car. up to now. missed-dose studies with combination CBP have been established in order to provide additional therapy focused on changes in CBP have not been conducted criteria in the assessment of cardiovascular risk. hypertensive treatment.20 Moreover. The use of single-pill combinations with 2 or more anti- diovascular morbidity and mortality has been claimed. atenolol/bendroflumethiazide combination in preventing and non-insulin–dependent DM. recent was lower than those that were necessary to achieve the evidence suggests a superior reduction in CBP in favor of requested statistical power in the main trial. longer-lasting treatment effect in favor of the OLM-based age has been recently emphasized. central systolic blood pressure. the PER/AML combination was superior to the Patients with a long-lasting history of hypertension. In addition. PER. The number of patients AML and PER/AML combinations lower BP effectively in reported. which might leave tude as they lower PBP.34 Then. not all the drug classes employed in the man. However. and the OLM/AML combination. treatment effect along 24 weeks).org/ at University of Otago on June 3. CSBP.

AIx is considered a parameter that J. Jaarsma T. Pannier B. Pencina MJ. Circulation 2001.36 The pharmacological effect of both drugs is long lasting. however. Hypertension (ESH) and of the European Society of Cardiology (ESC). Botha J. 2016 wave. Gismondi RA. Redón J.43 Arteriograph and Vicorder. Treatment of hypertension in dia- tory of DM. Narkiewicz K. Waeber B. Bedirian R. Mirenda V. Vascular 2012. Hypertension 2008. 8. Pichler G. Viberti G. AJ. patients with preexisting coronary heart disease. 20:342–349. as a NM. nevertheless. Can J Cardiol 2014. and a worse glycemic control compared to the betes: what is the best therapeutic option? Expert Rev Cardiovasc Ther present study. 2012. Dart AM.42 Interestingly. Cifkova R. Fagard R. is 13 hours and ACKNOWLEDGMENTS more than 30 hours. and its measurement accuracy is acceptable Ferber P. and incident hypertension. Sirnes PA. Task Force Members. Solaz E. J Renin Angiotensin treatment was observed. however. 2013 ESH/ESC results cannot be extrapolated to the general population. Pozzobon CR. stage renal failure. the Viigimaa M. ARB.oxfordjournals. Vita JA. Skårn SN. Ruilope LM. Both treatments maintained anti. Pulse wave velocity and the non-invasive methods used to assess it: Complior. Benjamin EJ. Benjamin EJ. Bailey MA.39–41 Angiotensin II plays 2. Böhm M. The enrolled population consisted of hyper. assessment. Trudeau L. Christiaens T. has been a speaker for Menarini International.44 However. which is dependent on several mechanisms includ- ing peripheral vascular resistance. Central blood pressure as an index of antihypertensive con- beyond the BP-lowering effect of the drug is a matter that trol: determinants and potential value. J Hypertens 2014. the differences The work has been funded by Menarini International. rior to the PER/AML combination in reducing CBP and Neves MF. 48:80–86.45 betes independently of blood pressure lowering. Galderisi M. and no serious 5. Griffin KJ. and this is the main objec- tive of the present study. Hamburg discussion due to the results of the ROADMAP trial.  has no conflicts of interest to declare. EUDRA-CT Nº: 2010-018774-21. Smith A. Carotid-femoral pulse wave velocity assessment by two different meth- The use of OLM in diabetic patients has been a matter of ods: implications for risk assessment. Karalliedde J. Boutouyrie P. G. Sleight P. Valsartan improves arterial stiffness in type 2 dia- compared to direct invasive CBP estimation. OLM/AML combination provides longer-lasting efficacy Brachial pressure-independent reduction in carotid stiffness after long- in terms of CBP reduction compared to the PER/AML term angiotensin-converting enzyme inhibition in diabetic hyperten- combination. the active metabolite of PER. Blacher J. Nilsson PM. JAMA 2012. Vita JA. Aksnes TA. 51:1617–1623. Laloux B. radicals in the vessel wall. Mitchell GF. 121:505–511. Rong J. In summary. Mitchell GF. SphygmoCor. than treatment with a combination of medium-dose ARB 4. changes due to pulsatile stress by regulating oxygen free 3. 6. Laurent S. 10:727–734. The present study must be considered within its strengths 9. Safar ME. Szarski M. and a trend of efficacy in favor of the OLM-based and hypertension: a randomized controlled trial. and its predictive value in DISCLOSURE cardiovascular risk has been demonstrated in numerous studies. Meredith IT. Kaess BM. 7.oxfordjournals. in a study treat. Ladeira MC. DeAngelis L. 30:S23–S28.  P. 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