Long-term Antihypertensive Efficacy Research Articles

THE ERYTHROCYTE MEMBRANES BETA-ADRENOREACTIVITY CHANGES AFTER RENAL DENERVATION AS A PROGNOSTIC FACTOR FOR THE LONG-TERM ANTIHYPERTENSIVE EFFICACY OF THE INTERVENTION

Objective: To study the functional state of the sympathoadrenal system (SAS) assessed by the erythrocyte membranes beta-adrenoreactivity (beta-ARM) level, 7 days and 2 years after renal denervation (RD), to assess the prognostic capabilities of this indicator in relation to the long-term antihypertensive efficacy of the treatment. Design and method: The study included 48 patients, 18 men and 30 women with resistant hypertension (RH) on stable antihypertensive therapy. The levels of mean daily systolic (SBP) and diastolic blood pressure (DBP), and level of beta-ARM at baseline, 7 days and 2 years after RD were studied. The beta-ARM determination based on erythrocytes hemolysis inhibition by the beta-blocker adding in hypoosmotic medium, that prevents their destruction by binding to erythrocyte membranes beta-adrenergic receptors. An increase in the beta-ARM value reflects a decrease in erythrocyte membranes beta-adrenergic receptors number on the background of prolonged sympathetic hyperactivation. Results: The average daily blood pressure levels decreased from 160.4 ± 16.0/88.1 ± 14.6 mm Hg to 145.3 ± 19.3/79.4 ± 13.6 mm Hg (p = 0.000) for 2 years. The beta-ARM dynamics was as follows: 43.8 ± 19.9 conventional units (CE) initially, decreased to 40.5 ± 17.0 CE after 7 days (p > 0.05), and increased to 55.3 ± 19.0 CE (p = 0.008) after 2 years. At the same time, the beta-ARM decrease after 7 days was significant in the responders group (p = 0.028), whose blood pressure after 2 years decreased by 10 mm Hg or more, and was absent in the non-responders group. There was a correlation between the dynamics of beta-ARM after 7 days and SBP and DBP after 2 years (r = -0.54, p < 0.05). This makes it possible to predict the RD long-term effectiveness. Conclusions: The decrease in beta-ARM 7 after RD indicates the effectiveness of the procedure and allows us to expect a significant blood pressure decrease in the long term after surgery. Nevertheless, 2 years after RD a decrease in the erythrocyte membranes adrenergic receptors density is observed, probably through a negative feedback mechanism in response to ongoing sympathetic stimulation even against the background of a blood pressure decrease

LONG-TERM EFFICACY AND SAFETY OF SPIRONOLACTONE IN THE TREATMENT OF RESISTANT ARTERIAL HYPERTENSION

Objective: Spironolactone is recommended as a fourth line antihypertensive drug by current hypertension guidelines. However, data about its long-term efficacy and safety is limited. Design and method: We prospectively followed 274 patients with resistant arterial hypertension who started treatment with spironolactone between September 2007 and December 2016. Change of office and ambulatory blood pressure (BP) between baseline and the last clinical examination was recorded, as well as the duration of spironolactone use, its dose, changes of other antihypertensive medications, laboratory parameters and the incidence of adverse events. Results: Patients were followed for an average of 35 (± 29) months, the mean daily dose of spironolactone was 27.5 mg. Mean office BP decreased during follow-up from 149/87 mmHg to 136/80 mmHg by a mean 13/7 mmHg (P < 0.001 for both). Mean 24-hour, day-time and night-time ambulatory BP decreased by 12/6 mmHg, 11/6 mmHg and 14/9 mmHg respectively (P < 0.001 for all). Adverse effects occurred in 72 patients (26.3%) and in 61 (22.2%) lead to discontinuation of spironolactone. Adverse events occurred more frequently in patients using angiotensin receptor blockers (hazard ratio – HR 1.65, P = 0.040), in the elderly (HR 1.38, P = 0.007) and patients with higher baseline serum creatinine (HR 1.12, P = 0.035). Conclusions: Our data confirm good long-term antihypertensive efficacy of spironolactone in patients who tolerate it. However, in more than a quarter of patients the use of spironolactone leads to side effects, which usually necessitate its discontinuation.

Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drugs treatment: a multicenter prospective study in China.

BackgroundGeneric drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.MethodsIn a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs.ResultsThere were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was –7.9 mmHg (95% CI, –9.9 to –5.9) in the brand-name drug group and –7.1 mmHg (95% CI, –9.1 to –5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2–2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.ConclusionsOur data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

Telmisartan

Telmisartan (Micardis), is a highly selective angiotensin II type 1 receptor antagonist, which is approved for the treatment of high blood pressure i.e, hypertension, either as monotherapy or in combination with other antihypertensive agents such as example hydrochlorothiazide. The long elimination half-life of telmisartan ensures the drug provides effect decrease in blood BP across the entire 24-hour dosage interval. From the well-designed clinical trials and the clinical practice that indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with co-existing type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. BP control is maintained throughout the 24-hour dosage interval, including during the last 6 hours of this period and it is recordable. Mainly in some conditions like pregnancy, renal impairment and in hepatic failure conditions it is not given.

0208: Efficacy of indapamide SR/amlodipine combination in uncontrolled hypertensive patients over 65 years old: a subanalysis of the 1-year NESTOR study

Guidelines recommend diuretics and calcium channel blockers (CCBs) to treat systolic hypertension in the older patient. This NESTOR substudy examines the antihypertensive effect of this combination in hypertensive diabetic patients aged ≥65 years. To evaluate the long-term antihypertensive efficacy and safety of indapamide SR/amlodipine in ≥65 year olds, in the randomized, double-blind, 1-year NESTOR study. The NESTOR study included 570 hypertensive (aged 35-80 years, systolic blood pressure [SBP] 140-180 and diastolic blood pressure [DBP] <110mmHg), diabetic patients with microalbuminuria, 187 of whom were aged ≥65 years. Antihypertensive therapy was stopped before inclusion and indapamide SR 1.5mg or enalapril 10mg administered. If target BP (<140/90mmHg) was not achieved at 6 weeks, amlodipine 5mg was added with uptitration to 10mg if needed. Follow-up period was 52 weeks. At 52 weeks in 107 patients aged ≥65 years receiving bitherapy, SBP/DBP decreased significantly (P<0.001) from baseline by 30±12/ 14±9mmHg with indapamide SR/amlodipine (n=53) vs 22±16/11±9mmHg with enalapril/amlodipine (n=54). There was a significantly greater SBP reduction of 6.2±2.7mmHg (P=0.02, adjusted on baseline) with indapamide SR/amlodipine vs enalapril/amlodipine, a larger difference than that seen in all ages on bitherapy (4.1±1.5mmHg; P=0.006). Moreover, BP response rate (<140/90mmHg or decrease of 20mmHg in SBP or 10mmHg in DBP) in ≥65 year olds was greater with indapamide SR/ amlodipine (88%) than with enalapril/amlodipine (75%). Indapamide SR and amlodipine were associated with a good safety profile. Three patients in each group discontinued treatment. This analysis confirms that a thiazide-like diuretic/CCB combination (indapamide SR/amlodipine) more effectively lowers SBP than an angiotensin-converting enzyme inhibitor/CCB combination in these hypertensive patients aged ≥65 years, whilst maintaining a good safety profile. Abstract 0208 – Figure

GW24-e0982 Long-term antihypertensive efficacy of extended-release nitrate for isolated systolic hypertension in elderly patients: a systematic review

ObjectivesThe aim of this systematic review was to assess the antihypertensive efficacy of extended-release nitrate for isolated systolic hypertension in elderly patients.MethodsThe electronic databases searched were the Database of s...

Position of indapamide, a diuretic with vasorelaxant activities, in antihypertensive therapy

Introduction: Diuretics play a pivotal role in the management of hypertension. A large experience has been accumulated with indapamide, a long-acting thiazide-like diuretic that lowers blood pressure (BP) primarily through its natriuretic diuretic effect. Some of its long-term antihypertensive efficacy may be due to calcium antagonist-like vasorelaxant activities. Indapamide has protecting effects in a variety of conditions associated with high cardiovascular risk, such as diabetes, left ventricular hypertrophy, nephropathy and stroke. It is highly effective in lowering BP, whether given alone or in combination. Indapamide is well tolerated and has the advantage of having no adverse impact on glucose and lipid metabolism. Today, thiazide-like diuretics are regarded more and more as preferred drugs, when diuretic therapy is required to lower BP.Areas covered: The aim of this paper is to review the experience accumulated with indapamide. It is limited to clinical studies that are relevant for the everyday management of hypertensive patients, whether or not they exhibit cardiovascular or renal disease.Expert opinion: Indapamide, because of its well-documented beneficial effects on cardiovascular and renal outcomes, represents a safe and valuable option for treating patients with high BP. There is, however, still room for new trials evaluating the combination of this diuretic with other types of antihypertensive drugs, in particular a calcium antagonist such as amlodipine. There is also the need to compare the indapamide–perindopril and indapamide–amlodipine combinations, in terms of antihypertensive efficacy, tolerability and effects on target organ damage and, ideally, on cardiovascular mortality.

Long-term Antihypertensive Efficacy of Losartan/Hydrochlorothiazide Combination Therapy on Home Blood Pressure Control

Angiotensin receptor blocker (ARB)/hydrochlorothiazide (HCTZ) combination therapy has been shown to produce a prompt reduction in clinic blood pressure (BP) without serious adverse effects; however, long-term antihypertensive efficacy on home BP has not been fully investigated. In this open-label multicenter observational study, a total of 151 hypertensive patients uncontrolled with antihypertensive regimens including standard dose of ARBs were switched to the fixed-dose combination of losartan (50 mg)/HCTZ (12.5 mg) (mean age 66.9 ± 9.5 years, 51% male, 19% with diabetes mellitus, and 57% with dyslipidemia). After 3 months, losartan/HCTZ treatment significantly reduced mean home systolic BP/diastolic BP from a baseline level of 153 ± 11/85 ± 9 mm Hg to 136 ± 12/77 ± 10 mm Hg (P < .001) and mean clinic BP from 158 ± 9/87 ± 9 to 136 ± 12/77 ± 10 (P < .001), which were maintained through the study period of 12 months (132 ± 11/75 ± 9 and 136 ± 12/77 ± 10; home and clinic BP at 12 months, respectively, P < .001). Furthermore, younger patients (<65 years) receiving ARB monotherapy at the start of the study showed a significantly greater reduction in home BP, but not in clinic BP, compared with elderly patients (≥65 years). In conclusion, losartan/HCTZ combination therapy exerted a 1-year long-term efficacy on home BP as well as clinic BP. In patients uncontrolled with ARB monotherapy, the antihypertensive efficacy on home BP is more pronounced in younger patients compared with that in elderly patients.

Combination Delapril/Manidipine as Antihypertensive Therapy in High-Risk Patients

The majority of patients with hypertension, and in particular high-risk patients or those with diabetes mellitus or renal dysfunction, are likely to require combination therapy with at least two antihypertensive agents (from different classes) to achieve their blood pressure (BP) target. The delapril/manidipine fixed-dose combination consists of two antihypertensive agents with different, yet complementary, mechanisms of action. Delapril/manidipine has demonstrated short- and long-term antihypertensive efficacy in a number of clinical studies in patients with hypertension with an inadequate response to monotherapy. Comparative studies have demonstrated that delapril/manidipine is as effective as enalapril/hydrochlorothiazide (HCTZ) in patients with hypertension with an inadequate response to monotherapy, and as effective as irbesartan/HCTZ, losartan/HCTZ, olmesartan medoxomil/HCTZ, ramipril/HCTZ and valsartan/HCTZ in reducing BP in patients with hypertension and diabetes, or in obese patients with hypertension. Therapy with delapril/manidipine also appears to exert beneficial effects that extend beyond a reduction in BP, including nephroprotective activity and an improvement in fibrinolytic balance, supporting its value as a treatment option in these patient populations at high or very high cardiovascular risk because of the presence of organ damage, diabetes or renal disease.

Practitioner's Trial on the Efficacy of Antihypertensive Treatment in Elderly Patients with Hypertension II (PATE‐Hypertension II study) in Japan

Reduction of elevated blood pressure (BP) has been an important treatment goal in elderly hypertensive patients. However, it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients. We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy, tolerability and impact on cardiovascular/cerebrovascular (CV) morbidity/mortality in a large cohort of Japanese patients. This study was performed at general practitioners' offices nationwide with a target sample size of 1500 patients. Hypertensive patients aged 60years or more who achieved successful BP control with candesartan monotherapy, and who tolerated the treatment for at least 8weeks, were enrolled into the study and followed for 3years. BP was maintained below the target level of 140/90mmHg over the 3-year period. The incidence of CV events during the study period was 20.4/1000person-years. Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events. However, very elderly patients (≥75years) with a systolic BP (SBP) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120-139mmHg. This study demonstrated that treatment with candesartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events. CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older, which suggests that excessive BP reductions might be harmful for very elderly patients.

Long-term safety and efficacy of aliskiren and valsartan combination with or without the addition of HCT in patients with hypertension

Objective:To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320 mg combination.Methods:This was a 54-week, multicenter, open-label study (core phase), followed by a 26-week extension phase. Efficacy variables were change in msDBP and msSBP from baseline to endpoint (54-week and 80-week). Safety was assessed by monitoring and recording adverse events (AEs). ClinicalTrials.gov Identifier: NCT00386607Results:A total of 601 patients (msDBP ≥90 and <110 mmHg) entered the 54-week core study. Optional add-on HCT was allowed at week 10 onwards if BP was ≥140/90 mmHg at two consecutive visits. Of the 486 patients completed the core study, 180 patients entered the extension phase and received aliskiren/valsartan and add-on HCT (12.5 or 25 mg). Overall the combination of aliskiren/valsartan was well-tolerated and the majority of AEs were mild-to-moderate in severity. The incidence of SAEs was low (core phase: n = 22 [3.7%]; extension phase: n = 4 [2.2%]). Elevated serum potassium (>5.5 mmol/L at any time during the study) was observed in 21 (3.6%) patients. The majority of these elevations were transient and returned to normal in subsequent visits, and the discontinuation rate due to elevated serum potassium was low (0.3% [n = 2]). Decreased serum potassium levels (<3.5 mmol/L at any time during the study) was observed in 26 (4.4%) patients, mainly in patients receiving aliskiren/valsartan/HCT (n = 22; 7.1%). At the 54-week endpoint, a mean BP reduction of 20.5/13.4 mmHg from baseline (baseline BP: 152.9/97.0 mmHg) was observed and 66.9% (n = 398/595) of patients achieved BP control with aliskiren/valsartan with or without HCT. At the end of the extension phase (80-week endpoint), additional reduction in BP was obtained (overall, 28.8/18.3 mmHg) and 86.6% (n = 155/179) of patients achieved BP control with aliskiren/valsartan/HCT. A limitation is the absence of an active comparator group.Conclusion:Long-term treatment with the combination of aliskiren/valsartan with or without HCT provided clinically meaningful BP reductions and high rates of BP control and was well-tolerated.Trial registration: ClinicalTrials.gov identifier: NCT00386607.

Improving quality of life in hypertension management using a fixed-dose combination of olmesartan and amlodipine in primary care

Objectives. To assess quality of life (QoL) in unselected patients in primary care treated with a fixed-dose combination of olmesartan and amlodipine.Research design and methods. Multicenter, noninterventional, noncontrolled observational study in 8241 patients seen by 2187 physicians over 12 – 18 weeks.Main outcome measures. Changes in QoL were assessed by using the Short Form 12 (SF-12) questionnaire completed by 5434 patients (65.9%) at baseline and 4924 patients (59.8%) at the follow-up visit.Results. Patients had a mean age of 62.8 ± 11.8 years (48.1% female), mean blood pressure [BP] at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg and 74.8% had at least one co-morbid risk factor or condition. All 12 items of the SF-12 improved over the observational period (p < 0.0001) as did the physical (46.8 vs 40.4; p < 0.0001) and mental summary scores (52.4 vs 47.5; p < 0.0001). Correlations of changes in systolic and diastolic BP, pulse pressure and heart rate with scores were significant, although weak (maximum -0.2055 for physical health and changes in systolic blood pressure).Conclusions. The fixed-dose combination of olmesartan and amlodipine significantly improves QoL in an unselected population of patients in primary-care practice. This might translate into improved patient compliance and improved long-term antihypertensive efficacy.

One-year effectiveness and safety of open-label losartan/hydrochlorothiazide combination therapy in Japanese patients with hypertension uncontrolled with ARBs or ACE inhibitors

The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan.

The Choice of Thiazide Diuretics

Thiazide diuretics were introduced in the United States for the treatment of hypertension in 1957. The first of these, chlorothiazide, was soon accompanied by a large number of other sulfonamide derivatives, including chlorthalidone. Hydrochlorothiazide (HCTZ) rapidly became the most commonly prescribed antihypertensive drug in the United States, whereas bendroflumethiazide was most popular in the United Kingdom. The initial popularity of HCTZ in the United States was abetted by its use in the first controlled trial of the treatment of nonmalignant hypertension, the Veterans’ Affairs Cooperative Study.1 The starting dose of HCTZ was 50 mg/d, and it was used along with reserpine and hydralazine. A number of other trials published in the 1970s all used higher doses of diuretic, for example, ≥50 mg of HCTZ per day.2 For reasons unknown to me, chlorthalidone was chosen to be the diuretic in the first large controlled trial of the treatment of hypertension, the Hypertension Detection and Follow-Up Program.3 In the Hypertension Detection and Follow-Up Program, all 10 940 patients were started on chlorthalidone from 25 to 100 mg/d. Other drugs were added to achieve control of the blood pressure. In addition, half were assigned to “referred” care and the other half to more closely monitored and intensively treated “stepped” care. The stepped care–treated half achieved a 4.4% further reduction in diastolic blood pressure and a 17.0% reduction …

Long-Term Antihypertensive Efficacy and Safety of the Oral Direct Renin Inhibitor Aliskiren

Diuretics are recommended as first-line agents for the treatment of hypertension. This randomized, double-blind, multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension. After a 2- to 4-week placebo run-in, 1124 patients (mean sitting diastolic blood pressure [BP] 95 to 109 mm Hg) were randomized to aliskiren 150 mg (n=459), hydrochlorothiazide 12.5 mg (n=444), or placebo (n=221) once daily. Forced titration (to aliskiren 300 mg or hydrochlorothiazide 25 mg) occurred at week 3; at week 6, patients receiving placebo were reassigned (1:1 ratio) to aliskiren 300 mg or hydrochlorothiazide 25 mg. From week 12, amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled. Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method. BP reductions (mean sitting systolic BP/mean sitting diastolic BP) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 (-20.3/-14.2 versus -18.6/-13.0 mm Hg; P<0.05) and were also greater at week 52 (-22.1/-16.0 versus -21.2/-15.0 mm Hg; P<0.05 for mean sitting diastolic BP). At the end of the monotherapy period (week 12), aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP (-17.4/-12.2 versus -14.7/-10.3 mm H; P<0.001). Adverse event rates were similar with aliskiren- (65.2%) and hydrochlorothiazide-based therapy (61.5%). Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy (17.9% versus 0.9%; P<0.0001). Aliskiren treatment, both as monotherapy and with optional addition of amlodipine, provided significantly greater BP reductions than the respective hydrochlorothiazide regimens. Aliskiren-based therapy was well tolerated. Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension.

Pharmacoeconomics and quality of life analysis of telmisartan in hypertension treatment

Hypertension is a major public health problem, being one of the leading causes of death and disability worldwide and a major risk factor for cardiovascular disease. The renin–angiotensin–aldosterone system plays an important role in volume homeostasis and blood pressure regulation, and is a target for several groups of pharmaceutical agents. Telmisartan, a highly selective AT1 receptor antagonist, fulfills all new criteria for antihypertensive agents: high effectiveness, high specificity, high compliance and fewer adverse effects. Several clinical trials and the clinical practice setting indicate substantial evidence that telmisartan, either as monotherapy or in combination with other antihypertensive drugs, provides long-term antihypertensive efficacy. In fact, telmisartan has the property to sustain blood pressure control throughout the 24-h dosage interval. Furthermore, telmisartan can play an important role in improving compliance, because of its documented good tolerability profile, which limits the adverse effects. This article provides the most recent data of the pharmacoeconomic position of telmisartan and its treatment effects on quality of life.

Telmisartan

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.

Peripheral sympatholytic actions of four AT1 antagonists: are they relevant for long-term antihypertensive efficacy?

Angiotensin II causes hypertension not only by direct constriction of vascular smooth muscle, but also by facilitating the release of noradrenaline from sympathetic terminals and by enhancing vascular noradrenaline sensitivity. AT1 receptor antagonists attenuate all these actions, but display some evidence of substance-related selectivities. The contribution of pre- or postsynaptic impairment of sympathetic transmission to long-term antihypertensive efficacy should be determined for four structurally different, clinically approved AT1 antagonists. Spontaneously hypertensive rats were treated with candesartan, eprosartan, irbesartan, or losartan via osmotic minipumps for 4 weeks at doses yielding identical reductions of blood pressure. Maximum efficacy was obtained with a tripled dose of candesartan. In the pithed rat model, stimulus/response dependencies were determined for vasopressor effectivity of preganglionic electrical stimulation, and of intravenous bolus applications of noradrenaline and angiotensin II. Losartan, irbesartan, eprosartan, and candesartan at doses of 5, 40, 20, and 0.05 mg/kg per day, were equally effective in reducing basal systolic blood pressure (-42 mmHg), and the vasopressor potency of angiotensin II (approximately 10-fold). The efficacies of preganglionic stimulation and exogenous noradrenaline were unaltered, with the exception of irbesartan, which reduced vascular noradrenaline sensitivity. The tripled dose of candesartan further reduced basal and angiotensin II-stimulated blood pressures, and significantly attenuated vascular noradrenaline sensitivity. AT1 antagonists at doses that effectively reduce blood pressure in chronic therapy do not generally suppress peripheral sympathetic function. A potential interaction consists in a reduction of vascular noradrenaline sensitivity, which can be considered as a class effect of AT1 antagonists at high dosage.

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients

ABSTRACTObjective: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (≥ 65 years).Study design: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg.Results: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was –24.0/–13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP ≤ 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP ≥ 10 mmHg or in supine systolic BP ≥ 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3–M15), whatever the previous treatment received during the 3-month, double-blind period (M0–M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported.Conclusion: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years–80 years with systolo-diastolic hypertension (SDH) or ISH.

Evaluation of long-term efficacy of indapamide SR 1.5 mg in elderly hypertensive patients

To assess the long-term antihypertensive efficacy and acceptability of indapamide (IDP) SR 1.5mg over 1 year, in a population of hypertensive patients aged > 65 years, including those with isolated systolic hypertension (ISH). An open 12-month follow-up with IDP was carried out in patients who were responders and/or normalized at the end of a 3-month randomized, controlled, double-blind study with IDP SR 1.5 mg, amlodipine (AML) 5 mg or hydrochlorothiazide (HCTZ) 25 mg, in which a similar short-term antihypertensive efficacy of the three medications was observed, with a greater efficacy of IDP versus HCTZ in the subgroup of patients with ISH. The long-term study included 444 patients (24% ISH) aged 72.3 ± 6.1 years. Blood pressure (BP) remained steady through the study, and the 12-month treatment resulted in 80.1% normalized and 81.5% responder patients. In ISH subgroup, no significant change in systolic/ diastolic BP was observed and the treatment resulted in 84.3% BP normalization. In the intention-to-treat population (n=435), according to previous treatment groups during the 3-month double-blind period, IDP was also demonstrated to constantly control both systolic and diastolic BP, and the systolic BP in ISH patients. In the IDP and AML groups, 1-year treatment with IDP led to minor further decreases in BP; in HCTZ group, there was a trend toward lower BP values during IDP treatment (table). Low incidence of adverse drug reactions(5%)and 1.6% withdrawals due to drug-related adverse events were observed. ITT: intention-to-treat population; HCTZ: hydrochlorothiazide; AML: amlodipine; Δ: change from baseline ITT: intention-to-treat population; HCTZ: hydrochlorothiazide; AML: amlodipine; Δ: change from baseline Indapamide SR 1.5 mg presents excellent long-term antihypertensive efficacy and tolerability in elderly hypertensive patients, especially in ISH patients.