Management of hypertension with fixed dose combinations of candesartan cilexetil and hydrochlorothiazide: patient perspectives and clinical utility

Hypertension treatment and control is largely unsatisfactory when guideline-defined blood pressure goal achievement and maintenance are considered. Patient- and physician-related factors leading to non-adherence interfere in this respect with the efficacy, tolerability, and convenient use of pharmacological treatment options. Blockers of the renin–angiotensin system (RAS) are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug–drug combinations of both principles like candesartan/hydrochlorothiazide (HCTZ) are highly effective in lowering blood pressure while providing improved compliance, a good tolerability, and largely neutral metabolic profile. Comparative studies with losartan/HCTZ have consistently shown a higher clinical efficacy with the candesartan/HCTZ combination. Data on the reduction of cardiovascular endpoints with fixed dose combinations of antihypertensive drugs are however scarce, as are the data for candesartan/HCTZ. But many trials have tested candesartan versus a non-RAS blocking comparator based on a standard therapy including thiazide diuretics. The indications tested were heart failure and stroke and particular emphasis was put on elderly patients or those with diabetes. In patients with heart failure, for example, the fixed dose combination might be applied in patients in whom individual titration resulted in a dose of 32 mg candesartan and 25 mg HCTZ which can then be combined into one tablet to increase compliance with treatment. Also in patients with stroke the fixed dose combination might be used in patients in whom maintenance therapy with both components is considered. Taken together candesartan/HCTZ assist both physicians and patients in achieving long-term blood pressure goal achievement and maintenance

Office and ambulatory blood pressure control with a fixed-dose combination of candesartan and hydrochlorothiazide in previously uncontrolled hypertensive patients: results of CHILI CU Soon

Thomas Mengden1, Reinhold Hübner2, Peter Bramlage31Kerckhoff-Klinik GmbH, Bad Nauheim, 2Takeda Pharma GmbH, Aachen, 3Institut für Kardiovaskuläre Pharmakologie und Epidemiologie, Mahlow, GermanyBackground: Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ) have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP) values obtained during office measurement (OBPM) with ambulatory blood pressure measurement (ABPM).Methods: CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged ≥18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented.Results: A total of 4131 patients (52.8% male) with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P < 0.0001 for both comparisons). BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours), ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (<130/80 mmHg). The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day). Of those who were normotensive upon OBPM, 35.1% had high ABPM during the day, 49.3% were nondippers, and 3.4% were inverted dippers. Forty-nine adverse events (1.19%) were reported, of which seven (0.17%) were regarded as serious.Conclusion: Candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ is safe and effective for further BP lowering irrespective of prior antihypertensive drug class not being able to control BP.Keywords: ambulatory blood pressure, office blood pressure, normalization, respons

An Evaluation of Self-Measured Blood Pressure in a Study With a Calcium-Channel Antagonist Versus a β-Blocker

In recent years self-measurement of blood pressure at home has gained increasing importance but there have been only a few studies comparing casual, ambulatory, and self-measured blood pressure determinations during a single clinical trial. We therefore compared treatment-induced blood pressure-reductions in a double-blind, placebo-controlled, parallel study design with a single morning dose of either 10 mg bisoprolol (n = 26) or 20 mg nitrendi-pine (n = 27) with casual blood pressure readings in the morning before the dose, ambulatory 24-h monitoring, and self-recorded measurements in the morning before the dose and in the evening. Mean reductions for systolic and diastolic blood pressure after 4 weeks of therapy were significantly greater for bisoprolol than for nitrendipine. The treatment-induced blood pressure reductions were most pronounced as assessed by casual readings but showed good agreement between casual, ambulatory, and self-measured blood pressure for group comparisons. In some patients, however, marked individual differences between the three methods were observed. Correlation coefficients between ambulatory and self-measured blood pressure were 0.4 for systolic blood pressure (P < .05) and 0.6 for diastolic blood pressure (P < .0005). Under the conditions of this parallel study design and the usual statistical risks, a difference of 5 mm Hg in diastolic blood pressure can be detected in 118 patients at the clinic, in 70 patients if ambulatory blood pressure is used, or in 56 patients if self-measured blood pressure is used. In conclusion, bisoprolol was more effective over 24 h than nitrendipine at the doses studied. Furthermore, self-measured blood pressure was suitable for monitoring 24-h efficacy of the two antihypertensive drugs under investigation. Finally, self-measured blood pressure can substantially improve the sensitivity of hypertension trials in comparison to casual readings and therefore reduce the number of patients included. Am J Hypertens 1992;5:154-16

Management of patients with uncontrolled arterial hypertension – the role of electronic compliance monitoring, 24-h ambulatory blood pressure monitoring and Candesartan/HCT

Abstract Background Incomplete drug regimen compliance (DRC) and white-coat hypertension are two of several possible causes of uncontrolled hypertension. Therefore the aim of the present study was to compare DRC in hypertensives treated with combination therapy whose blood pressures (BP) were controlled vers. uncontrolled after 4 weeks of self-monitored BP measurement. To observe the consequences in uncontrolled patients of switching one drug of the combination therapy to candesartan/HCTZ (16 mg/12.5 mg) with and without a compliance intervention program. Methods Self-and ambulatory-monitoring of BP were done with upper arm oscillometric devices. Patients' dosing histories were compiled electronically (MEMS(c), AARDEX). Patients with office blood pressure (OBP) >140/90 mmHg despite combination therapy were begun on MEMS monitoring and self BP measurement for 4 weeks of run-in. Of 62 such patients, 18 (29%) patients were normotensive according to self BP measurement and ambulatory BP measurement at 4 weeks (Group A); in the remaining 44 still uncontrolled patients, candesartan/HCTZ was substituted for one of the combination therapy drugs, with half these patients receiving passive compliance monitoring (B) and half a DRC intervention program (C). All groups were then followed for 8 weeks. Results DRC before week 4 was significantly higher in A than in the uncontrolled patients (B&C). DRC was stable during run-in A, but declined in B and C. DRC after week 4 was not different in the three groups and stayed constant over time. DRC during weekends was lower than during weekdays in all groups. In group A no significant change in blood pressure was observed with all three methods of BP measurements. In groups B and C significant reductions of systolic and diastolic BP were observed for ABPM and SBPM. After the change to candesartan/HCTZ in B&C ambulatory 24-h-BP (ABPM) was normalized in 39% of patients. Conclusion Normalization of BP was associated with superior drug regimen compliance in previously uncontrolled patients treated with a combination drug regimen. Switching still-uncontrolled patients to candesartan/HCTZ significantly improved BP control and stabilized a declining DRC.</p

Prehabilitation in patients awaiting elective coronary artery bypass graft surgery – effects on functional capacity and quality of life: a randomized controlled trial

Objective: To determine the impact of an exercise-based prehabilitation (EBPrehab) program on preand postoperative exercise capacity, functional capacity (FC) and quality of life (QoL) in patients awaiting elective coronary artery bypass graft surgery (CABG). Design: A two-group randomized controlled trail. Setting: Ambulatory prehabilitation. Subjects: Overall 230 preoperative elective CABG-surgery patients were randomly assigned to an intervention (IG, n=88; n=27 withdrew after randomization) or control group (CG, n=115). Intervention: IG: two-week EBPrehab including supervised aerobic exercise. CG: usual care. Main measures: At baseline (T1), one day before surgery (T2), at the beginning (T3) and at the end of cardiac rehabilitation (T4) the following measurements were performed: cardiopulmonary exercise test, six-minute walk test (6MWT), Timed-Up-and-Go Test (TUG) and QoL (MacNew questionnaire). Results: A total of 171 patients (IG, n=81; CG, n=90) completed the study. During EBPrehab no complications occurred. Preoperatively FC (6MWTIG: 443.0±80.1m to 493.5±75.5m, P=0.003; TUGIG: 6.9±2.0 s to 6.1±1.8 s, P=0.018) and QoL (IG: 5.1±0.9 to 5.4±0.9, P<0.001) improved significantly more in IG compared to CG. Similar effects were observed postoperatively in FC (6MWDIG: Δ-64.7m, pT1–T3=0.013; Δ+47.2m, pT1–T4<0.001; TUGIG: Δ+1.4s, pT1–T3=0.003). Conclusions: A short-term EBPrehab is effective to improve perioperative FC and preoperative QoL in patients with stable coronary artery disease awaiting CABG-surgery

ST segment depression in hypertensive patients: A comparison of exercise test versus Holter ECG

Sakir Uen1, Rolf Fimmers2, Burkhard Weisser3, Osman Balta1, Georg Nickenig1, Thomas Mengden11Division of Hypertension and Vascular Medicine, Department of Internal Medicine II, University Clinic, Bonn, Germany; 2Department of Biometry and Medical Statistics, University of Bonn, Bonn, Germany; 3Department of Sports Medicine, University of Kiel, Kiel, GermanyIntroduction: This study compared ST segment depression (ST depression) during cycle ergometry (ergometry) versus simultaneous 24-hour ambulatory blood pressure measurement and electrocardiogram recording (24-h ABPM/ECG) during everyday life.Methods: In a German multicenter study, ergometry and 24-h ABPM/ECG records of 239 hypertensive patients were retrospectively analyzed. ST depression was defined as an ST segment depression (1 mm limb or chest recordings V1 to V6) in an incremental cycle ergometry, or 1 mm in the 24-h ABPM/ECG recording under everyday conditions. Blood pressure parameters at the onset of ST depression in the context of the respective method were compared.Results: 18 patients had ST depression only in ergometry (group B), 23 had ST depression only during 24-h ABPM/ECG monitoring (group C) and 28 patients had ST depression with both methods (group D). Group A had no ST depression with any method. In group D, at the onset of ST depression with 24-h ABPM/ECG investigation, all parameters except diastolic blood pressure were significantly lower compared with the corresponding parameters at the onset of ST depression with ergometry (systolic blood pressure: 148 &plusmn; 19 vers 188 &plusmn; 35 mmHg, p &lt;&nbsp;0.001; heart rate: 93 &plusmn; 12 vs 120 &plusmn; 21 beat/min, p &lt;&nbsp;0.0001; double product: 13,714 &plusmn; 2315 vs 22,992 &plusmn; 3,985 mmHg/min), p &lt;&nbsp;0.0001).Conclusion: ST depressions during everyday life detected by 24-h ABPM/ECG are characterized by a substantially lower triggering threshold for blood pressure level parameters compared with ergometry. The two methods detecting ischemia do not replace but complement each other.Keywords: ST segment depression, arterial hypertension, blood pressure measurement, combined 24-h ABPM/ECGCorrigendum for this paper has been publishe