hypertension commonly accompanies other cardiovascular disease ( cvd ) risk factors and comorbidities such as obesity , chronic kidney disease , diabetes mellitus ( dm ) , and heart disease . in these high cvd risk patients , early treatment of hypertension to attain blood pressure ( bp ) goals may be particularly important in order to help reduce cvd risk . around three quarters of patients with hypertension will require combination therapy in order to reach guideline - recommended bp goals [ 2 , 3 ] . in high - risk hypertensive patients , the initial use of combination therapy may facilitate the achievement of bp goals   and help to lower the risk of target organ damage [ 2 , 58 ] .
this supports a strategy aimed at combining antihypertensive agents with complementary mechanisms of action [ 3 , 9 ] .
the combination of an angiotensin ii receptor blocker ( arb ) plus a thiazide diuretic is endorsed by international hypertension guidelines [ 4 , 5 ] . as a result of evidence from the ongoing telmisartan alone and in combination with ramipril global endpoint trial ( ontarget )
[ 10 , 11 ] , telmisartan is the only arb currently approved for the reduction of cvd morbidity in patients with manifest atherothrombotic cvd ( history of coronary heart disease ( chd ) , stroke , or peripheral arterial disease ) or type 2 dm with documented target organ damage .
a prior multinational , double - blind , and double - dummy study demonstrated that initial treatment with the single - pill combination ( spc ) of telmisartan 80  mg ( t80 ) plus hydrochlorothiazide ( hctz ) 25  mg ( h25 ) therapy in patients with grade 2 or 3 hypertension significantly reduced bp and produced higher bp goal attainment compared with t80 alone .
the large patient population in that study provided an opportunity for analysis of the response to telmisartan / hctz spc compared with t80 monotherapy treatment within different subpopulations of patients with grade 2 or 3 hypertension .
this current analysis evaluated the efficacy and tolerability of spc t80/h25 compared with t80 monotherapy in patients with cvd risk factors : presence of dm , renal impairment , increased body mass index ( bmi ) , and 10-year risk score for chd ( based on tertiles ) , with additional post hoc analyses according to alternative guideline - recommended 10-year chd risk groups .
the trial was performed as a 7-week , multinational , phase iv , randomized , double - blind , active - controlled , parallel - group , and forced - titration study in patients with grade 2 or 3 hypertension .
the trial was conducted between june 2009 and april 2010 ( clinicaltrials.gov identifier : nct00926289 ) .
the study design was described in detail elsewhere . in brief , after an open - label , placebo run - in treatment period of 114 days , patients were randomized 2  :  1 to double - blind treatment with spc telmisartan 40  mg ( t40)/hctz 12.5  mg or t40 monotherapy for 1 week before uptitration to the target dose of spc t80/h25 or t80 monotherapy , respectively , for the remaining 6 weeks .
the trial was conducted under the guidelines specified by the declaration of helsinki and international conference on harmonisation tripartite harmonised guidelines for good clinical practice .
the study protocol was approved by the health authority in each country and by the institutional review board or ethics committee of each center .
patients were recruited at 102 participating centers in eight countries ( bulgaria , china , france , georgia , romania , russia , south korea , and the united states ) .
eligible patients were men or women age 18 years with grade 2 or 3 hypertension ( mean seated in - clinic trough cuff systolic bp ( sbp ) 160  mm  hg and diastolic bp ( dbp ) 100  mm  hg ) who met the inclusion criteria ( described in detail elsewhere ) .
study exclusion criteria included mean sbp 200  mm  hg and/or dbp 120  mm  hg ; severe renal impairment ( serum creatinine > 3.0  mg / dl and/or creatinine clearance < 30  ml / min and/or clinical markers of severe renal impairment ) ; congestive heart failure ( new york heart association functional class iii or iv ) ; severe obstructive coronary artery disease ; aortic stenosis ; contraindications to a placebo run - in period ( e.g. , stroke within the past 6 months , myocardial infarction , cardiac surgery , percutaneous transluminal coronary angioplasty , unstable angina , or coronary artery bypass graft within 3 months prior to the start of the placebo run - in period ) ; and uncontrolled dm ( glycated hemoglobin 10% ) . in this analysis , patients were evaluated for inclusion into baseline cvd risk factor subgroups : dm , renal function , bmi , and 10-year chd risk score .
the dm subgroup included those with a diagnosis of type 1 dm , type 2 dm , diabetic retinopathy / nephropathy , or the presence of recognized medical dictionary for regulatory activities codes for dm .
renal function categories were defined by estimated glomerular filtration rate ( egfr ) < 60  ml / min/1.73  m or egfr 60  ml / min/1.73  m. bmi categories were defined as < 25  kg / m , 25<30  kg / m , or 30  kg / m . for 10-year chd risk score ,
the probability of developing chd over 10 years was estimated ( based on a risk score developed from the framingham heart study ) for all treated patients for whom a baseline laboratory value for total cholesterol and high - density lipoprotein ( hdl ) was available .
this risk score estimated the probability of developing chd over 10 years based on baseline values for age , gender , total cholesterol and hdl , bp category , presence of dm ( yes / no ) , and smoking status ( yes / no ) .
the method used in this analysis to assess the 10-year risk for chd was based upon a version of the framingham risk score described by wilson et al . , which included dm as a measured parameter .
the prespecified analysis according to the trial statistical analysis plan divided chd risk by tertiles across the patient population , which provided 10-year chd risk cutoffs of < 3.62% , 3.62<8.66% , and 8.66% . an additional post hoc analysis assessed chd risk according to more conventional and established categories of low , medium , and high chd risk   defined as follows : chd risk category 1 ( chd1 ) < 10% , chd risk category 2 ( chd2 ) 10%<20% , and chd risk category 3 ( chd3 ) 20% . at each study visit
, seated trough cuff bp was measured approximately 24 hours ( 2030 hours ) after the last study drug intake , with the mean taken from three consecutive measurements performed approximately 2 minutes apart using a standard manual cuff sphygmomanometer or other validated device ( with cuff size conforming with american heart association guidelines ) .
bp measurements were performed at screening , at the start of the open - label placebo run - in treatment period , at the end of the run - in treatment period prior to randomization ( i.e. , at baseline ) , and then after 1 , 3 , 5 , and 7 weeks of double - blind treatment .
efficacy endpoints assessed at weeks 3 , 5 , and 7 were described previously   and included the primary endpoint measure of change from baseline to final visit ( week 7 ) in mean seated trough cuff sbp .
secondary and other endpoints included change from baseline to final visit ( week 7 ) in mean seated trough cuff dbp , the proportion of patients achieving overall bp goal ( defined as a mean seated trough cuff sbp / dbp < 140/90  mm  hg ) , the proportion of patients with dm achieving overall bp goal ( defined as a mean seated trough cuff sbp / dbp < 130/80  mm  hg ) , the proportion of patients achieving sbp goal ( mean sbp < 140  mm  hg ) , the proportion of patients achieving dbp goal ( mean dbp < 90  mm  hg ) , the proportion of patients with a mean seated trough cuff sbp reduction of > 30  mm  hg , and the proportion of patients with mean seated trough cuff sbp reduction of > 40  mm  hg .
the assessment of adverse events ( aes ) by risk group was not prespecified but is included here and included serious aes and those leading to treatment discontinuation , with intensity and causal relationship to the study treatment determined by the investigator .
the objective of these analyses was to investigate whether spc t80/h25 provided greater bp reductions compared with t80 monotherapy among patient subgroups of dm , renal impairment , and at specific cut - off values for bmi and 10-year risk score for chd .
efficacy analyses were performed on data from the full analysis set ( fas ) , defined as randomized patients who received at least one dose of double - blind trial medication , and for whom a baseline measurement and at least one postdose trough efficacy measurement during the high - dose double - blind treatment period were available .
safety analyses were performed on all randomized patients who received at least one dose of the allocated treatment .
the sample size of the trial was calculated to ensure sufficient statistical power to show superiority of spc t80/h25 over t80 monotherapy with respect to the primary and key secondary endpoints within the overall study population .
the subgroup analyses were not powered per se to determine the efficacy of sbp h25/t80 versus t80 according to the different patient subpopulations reported here or to test for treatment - by - subgroup interactions .
because this was an exploratory ,  proof of concept  analysis and because no adjustments were made to correct for multiplicity , the statistical models were not applied for the purpose of providing statistical significance .
p values were calculated for the interaction of subgroup and treatment and are considered statistically significant with a p value of < 0.05 .
these p values provide an indication of whether the differences between treatments differ across subgroup categories ( e.g. , bmi ) .
a restricted maximum - likelihood - based , mixed - effect model , and repeated measures approach ( using baseline and all available longitudinal observations at each postbaseline visit during the high - dose treatment phase ) was utilized for the primary endpoint analysis , as well as for changes from baseline in dbp .
this model included the fixed , categorical effects of treatment , country , week , and treatment - by - week interaction , subgroup , and treatment - by - subgroup interaction , with the continuous covariates of baseline mean seated trough cuff sbp or dbp , and baseline - by - week interaction .
the difference in least squares means of treatments ( spc t80/h25 versus t80 monotherapy ) with a 95% confidence interval ( ci ) was calculated for each subgroup .
the outcomes of proportion of patients achieving bp , sbp , and dbp goals , and substantial sbp reductions ( > 30 or > 40  mm  hg ) , were evaluated using logistic regression with fixed effects for treatment , country , subgroup , treatment - by - subgroup interaction , and the respective baseline value ( dbp or sbp ) as a covariate .
last trough observation carried forward was employed to account for missing data in the analysis of binary endpoints of bp goal achievement and bp reductions .
odds ratios ( ors ) with 95% cis were calculated and reported for the effect of spc t80/h25 versus t80 monotherapy in different patient subpopulations .
the baseline characteristics of the entire cohort of 888 patients randomized and treated in the study were previously described .
the efficacy analyses were performed on data from 285 patients in the t80 group and 573 patients in the spc t80/h25 group ( fas total , 858 ) .
compliance with trial medication was high in both treatment groups ( at least 96.6% of patients in either treatment group took 80% to 120% of their trial medication at each visit ) .
the baseline bp characteristics of different patient subpopulations according to treatment group are shown in table 1 .
more patients did not have a diagnosis of dm than those who had a diagnosis with dm ( treated set , n = 779 and n = 109 , resp . ) .
more patients had egfr 60  ml / min/1.73  m ( n = 824 ) compared with those with egfr < 60  ml / min/1.73  m ( n = 58 ) . regarding bmi , 188 treated patients had baseline bmi < 25  kg / m , 341 treated patients had bmi 25<30  kg / m , and 359 treated patients had bmi 30  kg / m .
the distribution of patients in low , medium , and high estimated 10-year chd risk categories is displayed in table 2 .
chd risk was , overall , well matched between the spc t80/h25 and t80 treatment arms .
the majority of patients within this study , 71.3% , were within the lower - risk chd1 category ( < 10% risk ) , 20.9% were in the medium - risk category ( 10%<20% risk ) , and 7.8% of patients were within the chd3 category ( 20% risk ) .
efficacy results for the entire study population at week 7 were previously reported in detail .
briefly , within the entire study population , at week 7 , spc t80/h25 therapy significantly reduced adjusted mean  standard error sbp / dbp from baseline ( 37.0  0.62/18.6  0.38  mm  hg ) compared with t80 monotherapy ( 28.5  0.88/15.4  0.55  mm  hg ( adjusted mean difference 8.5/3.2  mm  hg ; 95% ci , 10.6 , 6.4/4.5 , 1.9 ; p < 0.0001 ) ) .
more patients receiving spc t80/h25 achieved bp goals compared with patients receiving t80 monotherapy ( p < 0.0001 for all comparisons ) .
the observed adjusted mean reductions in sbp / dbp from baseline according to treatment group and patient subpopulations are shown in table 3 .
the ors and 95% cis for the proportions of patients achieving bp goal and for the proportions of patients achieving sbp reductions > 30 or > 40  mm  hg , for treatment with spc t80/h25 versus t80 , in the different patient subpopulations , are displayed in figures 2 and 3 , respectively .
no significant treatment by subgroup interactions were found between patients with dm and those without dm with respect to treatment differences in bp reductions and control rates ( table 3 and figures 1 , 2 , and 3 ) . at week 7 , t80/h25 produced greater sbp and dbp reductions compared with t80 monotherapy in patients with or without dm ( table 3 and figure 1 ) .
the proportion of patients with dm who achieved the guideline - based bp goal ( sbp / dbp < 130/80  mm  hg ) at week 7 was approximately twofold higher in the spc t80/h25 group compared with the t80 group ( 16.7% versus 8.8% , resp . ) . among those with dm compared to t80 , spc t80/h25 resulted in a greater percent achievement of the bp goal of < 140/90  mm  hg ( 52.8% versus 38.2% ) . in patients without dm , this standard bp goal ( sbp / dbp < 140/90  mm  hg ) was achieved in 55.9% of those patients receiving spc t80/h25 and 34.3% of those receiving t80 . in patients without dm ,
greater proportions of patients achieved sbp goal ( < 140  mm  hg ) and dbp goal ( < 90  mm  hg ) with spc t80/h25 therapy compared to t80 monotherapy ( sbp : 64.1% versus 43.0% ; dbp : 68.1% versus 51.8% ) . in patients with dm , sbp and dbp goal rates
were also higher in the spc t80/h25 group compared with the t80 group ( sbp : 58.3% versus 41.2% ; dbp : 66.7% versus 58.8% ) ( figure 2 ) . in patients without dm , a greater proportion achieved sbp reductions of > 30 or > 40  mm  hg from baseline to week  7 with spc t80/h25 therapy compared with t80 monotherapy ( > 30  mm hg : 68.7% versus 46.6% ;
> 40  mm  hg : 41.3% versus 23.1% ) . in patients with dm ,
these sbp reductions were also achieved in a higher proportion of patients receiving combination therapy versus t80 monotherapy ( > 30  mm hg : 62.5% versus 47.1% ; > 40  mm  hg : 34.7% versus 29.4% ) ( figure 3 ) .
no significant treatment - by - subgroup interactions were found between patients within different egfr categories with respect to treatment differences in bp reductions and control rates ( table 3 and figures 1 , 2 , and 3 ) .
the large cis for patients with low egfr may be related to the low sample size .
egfr is expressed in ml / min/1.73  m . at week 7 , t80/h25 produced larger sbp and dbp reductions compared with t80 monotherapy in patients within both egfr categories ( table 3 and figure 1 ) .
spc t80/h25 therapy also allowed higher rates of bp goal attainment ( < 140/90  mm  hg ) in patients with egfr 60 ( 55.7% compared with 35.5% for t80 ) and in patients with egfr < 60 ( 52.8% compared with 19.0% for t80 ) .
sbp goal attainment ( < 140  mm  hg ) was also higher in patients receiving spc t80/h25 compared with t80 monotherapy , regardless of baseline egfr ( egfr 60 : 63.8% versus 43.9% ; egfr < 60 : 55.6% versus 23.8% )
. the dbp goal of < 90  mm hg for patients with egfr 60 was more commonly achieved in the spc t80/h25 group ( 68.5% ) compared with the t80 group ( 53.1% ) . in patients with egfr < 60 ,
the rates of dbp goal attainment were 58.3% and 42.9% , respectively ( figure 2 ) .
sbp reductions > 30 and > 40  mm  hg were attained in more of the patients who received spc t80/h25 compared with t80 monotherapy , regardless of baseline egfr ( > 30  mm  hg : 68.7% versus 47.3% in patients with egfr 60 ; 55.6% versus 33.3% in patients with egfr < 60 ; > 40  mm  hg : 40.9% versus 24.4% in patients with egfr 60 ; 33.3% versus 9.5% in patients with egfr < 60 ) ( figure 3 ) .
no significant treatment - by - subgroup interactions were found between groups of patients within different bmi categories with respect to treatment differences in bp reductions and control rates ( table 3 and figures 1 , 2 , and 3 ) .
treatment with spc t80/h25 consistently produced greater reductions in sbp and dbp at week 7 compared with t80 monotherapy across all three baseline bmi categories ( table 3 , figure 1 ) . at week 7 , spc t80/h25 produced higher rates of bp goal attainment ( < 140/90  mm  hg ) versus t80 monotherapy across the three bmi categories ( bmi < 25 : 58.2% versus 45.8% ; bmi 25<30 : 59.3% versus 33.0% ; bmi  30 : 50.6% versus 30.6% ) .
the sbp goal ( < 140  mm  hg ) was more commonly achieved in the spc t80/h25 group compared with the t80 group ( bmi < 25 : 64.8% versus 55.9% ; bmi 25<30 : 65.0% versus 38.3% ; bmi  30 : 61.2% versus 40.5% ) .
the dbp goal ( < 90  mm  hg ) was also more commonly achieved in the spc t80/h25 group compared with the t80 group ( bmi < 25 : 71.3% versus 57.6% ; bmi 25<30 : 73.4% versus 54.8% ; bmi
a similar pattern was observed for sbp reductions of > 30  mm  hg , which were achieved in a greater proportion of patients receiving spc t80/h25 across all three bmi categories ( figure 3 ) .
the responses of patients within different 10-year chd risk categories with regard to treatment differences in sbp and dbp reductions are shown in table 3 for the post hoc guideline - driven chd risk categories and also for the prespecified subgroups of chd risk divided by tertiles .
ors for treatment differences in sbp / dbp reductions and control rates are displayed in figures 1 , 2 , and 3 for the guideline - driven chd risk categories .
no significant treatment - by - subgroup interactions were found . at week 7 , reductions in mean sbp and dbp were greater in patients receiving spc t80/h25 compared with t80 monotherapy across all three chd risk categories ( table 3 and figure 1 ) . at week 7 , spc t80/h25 produced higher rates of bp goal attainment ( < 140/90  mm  hg ) versus t80 monotherapy across the three chd categories ( chd1 : 58.6% versus 36.3% ; chd2 : 49.0% versus 37.3% ; chd3 : 38.5% versus 17.9% ) .
the sbp goal ( < 140  mm  hg ) was more commonly achieved in the spc t80/h25 group compared with the t80 group ( chd1 : 67.0% versus 45.6% ; chd2 : 54.8% versus 44.0% ; chd3 : 46.2% versus 21.4% ) .
the dbp goal ( < 90  mm hg ) was also more commonly achieved in the spc t80/h25 group compared with the t80 group ( chd1 : 69.8% versus 52.2% ; chd2 : 62.5% versus 54.7% ; chd3 : 61.5% versus 50.0% ) ( figure 2 ) .
a similar pattern was observed for sbp reductions of > 30  mm  hg , which were achieved in a greater proportion of patients receiving spc t80/h25 across all three chd categories ( figure 3 ) .
a summary of aes reported during the study according to patient subpopulations is provided in table 4 .
the proportion of patients experiencing treatment - related aes in spc t80/h25 and t80 monotherapy groups was low across most of the patient subpopulations .
the proportion of patients with aes leading to treatment discontinuation was low and comparable across almost all investigated patient subpopulations except the subpopulation of patients with chd3 ( two patients ( 6.7% ) had an ae that resulted in discontinuation within this group ) .
only one patient experienced a serious ae during the treatment period and that was in the t40 group prior to uptitration .
the overall proportion of patients reporting any ae during treatment with spc t80/h25 was 16.0% .
an increase in the rate of aes was not observed with the presence of dm , increasing bmi , or increasing chd risk .
the frequency of any ae was similar across many of the assessed subpopulations ; however , in the subpopulation of patients with dm , the rate was 6.9% , in patients with a low bmi < 25 
kg / m , the rate was 22.7% , and in patients with a low egfr < 60  ml / min/1.73  m , the rate was 33.3% . in the overall study population , and irrespective of cause , the five aes most frequently occurring under treatment with spc t80/h25 , as determined by number of patients receiving spc t80/h25 with this ae , were dizziness ( 1.9% of patients ) , nasopharyngitis ( 1.4% ) , pollakiuria ( 0.9% ) , vertigo ( 0.7% ) , and cough ( 0.7% ) . among patients with dm receiving spc t80/h25 , the most frequently reported aes , as determined by number of patients with this ae , each occurring in one patient ( 1.4% ) , were anal abscess , hypotension , elevated blood uric acid , cough , hypertriglyceridemia , and proctalgia .
in patients with egfr < 60  ml / min/1.73  m who received treatment with spc t80/h25 , the most frequently reported ae was dizziness ( n = 2 patients , 5.6% ) .
other aes occurring in this subpopulation with a frequency of 2.8% ( n = 1 patient ) were upper respiratory tract infection ( rti ) , nasopharyngitis , ear infection , headache , syncope , hypotension , cough , oropharyngeal pain , abdominal pain , irritable bowel syndrome , myalgia , osteoarthritis , asthenia , and polyp . in patients with bmi
 30  kg / m who received spc t80/h25 , the most frequent ae was nasopharyngitis ( n = 4 patients , 1.7% ) , followed by viral rti and constipation ( each n = 3 patients , 1.2% ) . in high chd risk patients ( chd3 , 20% ) , the most frequent aes , each with two patients ( 2.6% ) , were upper rti , headache , hiccups , pollakiuria , asthenia , and blood alkaline phosphatase increase .
the overall rate of aes deemed by the study investigator to be treatment related was 4.6% in the spc t80/h25 group .
a difference in the frequency of treatment - related aes compared with the overall study population was observed in patients with dm ( 2.8% ) , patients with egfr < 60  ml / min/1.73  m ( 16.7% ) , patients with bmi < 25  kg / m ( 7.8% ) , and patients in the middle chd risk category chd2 ( 6.5% ) .
the most frequent drug - related aes in the t80/h25 treatment arm were dizziness and pollakiuria ( each 0.7% ) , syncope , and blood uric acid increase ( each 0.5% ) . a breakdown of the frequencies of these four aes within each subpopulation is provided in table 5 .
the presented results reflect prespecified and post hoc subgroup analyses of efficacy and safety data obtained during a 7-week , multinational , phase iv , randomized , double - blind , active - controlled , parallel - group , and forced - titration study in patients with grade 2 or 3 hypertension . in this analysis ,
spc t80/h25 similarly reduced sbp and dbp across specific subgroups of patients with cvd risk factors of dm , being overweight / obese , renal impairment , and chd risk , and those without these cvd risk factors .
additionally , spc t80/h25 consistently provided greater reductions in sbp and dbp over 7 weeks compared with t80 monotherapy , irrespective of the presence or absence of these cvd risk factors .
spc t80/h25 increased rates of bp goal attainment in all cvd risk groups , including patients with renal impairment , and in overweight to obese patients .
patients with dm were approximately twice as likely to reach a guideline - based bp goal ( sbp / dbp < 130/80  mm  hg ) over 7 weeks with spc t80/h25 than with t80 monotherapy ( 16.7% versus 8.8% ) , although the sample size of patients with dm was small .
a limitation of this study is that it was designed with a relatively short duration of treatment ( 7 weeks ) . due to the aforementioned reasons
, the results obtained from these subgroup analyses should be interpreted under consideration of their exploratory character . however
, this is the first report on the efficacy of spc t80/h25 in specific patient subpopulations according to the presence or absence of cvd risk factors ( dm , being overweight / obese , renal impairment , and high chd risk ) .
bp control is important in all hypertensive patients but is especially pertinent in those with additional cvd risk factors , since elevated bp is associated with significant increases in cv risk .
it is recognized that combination therapy can reduce bp to a greater extent and achieve bp goals more promptly , so high - risk individuals are likely to benefit from protective interventions without any delay .
initial combination therapy is increasingly recommended by guidelines , particularly for patients with cvd risk factors , and well - tolerated combinations can facilitate improved treatment adherence , a key factor in achieving successful bp control .
outcome studies have demonstrated that for every 20  mm  hg reduction in sbp , there is a 4050% reduction in cvd .
the degree of bp reductions observed with spc t80/h25 during this study would be expected to reduce cvd morbidity and mortality among patients at high risk for cvd [ 5 , 6 ] .
these analyses indicate that spc t80/h25 is an effective and generally well - tolerated antihypertensive combination that is suitable for treating a wide range of patients with grade 2 or 3 hypertension , in the presence or absence of additional cvd risk factors .
these analyses indicate that in patients with grade 2 or 3 hypertension , spc t80/h25 consistently provided greater bp reductions and increased attainment of bp goals compared with t80 monotherapy among patient subgroups with cvd risk factors .
the majority of patients with hypertension will require combination therapy to reach bp goals [ 5 , 18 ] .
the results of this trial indicate that treatment with spc t80/h25 in patients with grade 2 or 3 hypertension provides greater bp reductions and higher rates of goal attainment compared with t80 monotherapy .
antihypertensive treatment with the t80/h25 single - pill combination is effective and generally well tolerated , irrespective of the presence of additional cvd risk factors .
 
 objective . report of prespecified and post hoc subgroup analyses of a randomized , controlled trial comparing telmisartan 80  mg / hydrochlorothiazide 25  mg ( t80/h25 ) combination therapy with t80 monotherapy , according to the presence of cardiovascular disease ( cvd ) risk factors . methods . 
 hypertensive patients were randomized ( 2  :  1 ) to receive t80/h25 or t80 for 6 weeks , following a 1-week , low - dose , and run - in period . 
 systolic blood pressure ( sbp ) and diastolic bp reductions and bp goal achievement were evaluated in patients with cvd risk factors : presence of diabetes mellitus ( dm ) , renal impairment , increased body mass index ( bmi ) , and 10-year estimated risk for coronary heart disease ( chd ) . results . in total 
 , 888 patients received treatment . 
 overall , t80/h25 therapy significantly reduced sbp more than t80 monotherapy , irrespective of patient subgroup . in patients with dm , renal impairment , high bmi , and high chd risk , 
 bp goal achievement rates ( < 140/90  mm  hg ) at week 7 , among those treated with t80/h25 , were 52.8% , 52.8% , 50.6% , and 38.5% , respectively . 
 more patients with dm reached a guideline - based bp goal ( < 130/80  mm  hg ) at 7 weeks with t80/h25 than with t80 monotherapy ( 16.7% versus 8.8% ) . 
 rates of treatment - related adverse events were low and comparable across patient subgroups . 
 conclusions . antihypertensive treatment with t80/h25 single - pill combination is effective and generally well tolerated , irrespective of the presence of cvd risk factors . 
1. Introduction
2. Patients and Methods
3. Results
4. Discussion
5. Conclusions