Antihypertensive Group Research Articles

WHAT CAN WE EXPECT USING ACE INHIBITOR RAMIPRIL IN PERSONS WITH HIGH CARDIOVASCULAR RISK AND EARLY DISORDERS OF CARBOHYDRATE METABOLISM? LESSONS OF DREAM TRIAL

Primary prevention of diabetes in persons with high cardiovascular risk is an actual problem. Results of DREAM trial are discussed. Influence of ACE inhibitor, ramipril, on risk of diabetes onset in patients with pre-diabetes and low cardiovascular risk is focused. Metabolic effects of other groups of antihypertensive drugs and their ability to prevent diabetes onset are compared. Ramipril three years therapy resulted in normalization in glucose level but did not have effect on frequency of diabetes onset. Change in life-style and regular usage of ACE inhibitor, ramipril, can contribute in normalization of glycemia level in patients with combination of pre-diabetes and arterial hypertension.

Antihypertensive drug utilization at health centres in a district of Istanbul

Since irrational use of antihypertensives has considerable clinical and economical consequences, this study was conducted to evaluate antihypertensive drug utilization in hypertension at seven State Health Centres in Istanbul. A total of 297 hypertensive patients who accepted to participate in the study were evaluated by a face-to-face questionnaire and a copy of their prescriptions were collected for prescription analysis. Angiotensin-converting enzyme (ACE) inhibitors (31.7%), calcium channel blockers (28.8%), diuretics (16.2%), beta blockers (7.5%) and others (15.8%) have been prescribed. There were no statistically significant relation between prescribed antihypertensive drug groups and gender, age, and NSAIDs co-prescribing. The most frequent comorbidity in hypertensive patients was diabetes mellitus (10.4%) and calcium channel blockers (35.5%) have been prescribed to them as a first antihypertensive medication. Average cost per prescription was $42.7 +/- 38.1. According to the patients' self-reporting, the majority of them (85%) were prescribed without a physical examination. The physicians failed to write the prescriptions appropriately; only 5% of the scripts contained all information about the drug(s) and use instructions in full format. The present study indicates that GPs working at primary healthcare centres were rational in terms of antihypertensive drug choice. However, they poorly applied rational pharmacotherapy principles such as (a) writing a "good" prescription which is easily readable by the pharmacist and the patient and that contains full essential information; (b) a medical examination of the patient to assess her/his current clinical condition; and (c) taking care of not prescribing drugs with potential interaction like antihypertensives and NSAIDs together.

Epidemiologie der arteriellen Hypertonie in Deutschland

The mortality rate from cardiovascular disease is higher in northern than southern Germany. To illuminate this further current epidemiological data on arterial hypertension were obtained and compared with previously collected data. The results were based on interview and measurement data of 25- to 64 year-old participants in the Study of Health in Pomerania (SHIP-0 1997 - 2001; n = 3,042), and three population-representative surveys in the region of Augsburg, Southern Germany (MONICA S2 1989/90 n = 3,966; MONICA S3 1994/95 n = 3,916; S4 1999-2001 [KORA-2000 n = 3,464]). Hypertension was defined according to the WHO/ISH guidelines as blood pressure levels of > or =140/90 mmHg or antihypertensive medication given the subjects with known hypertension. Antihypertensive medication was classified as recommended by the German Hypertension Society. Currently, 57 % (95 % confidence intervall [CI] 54-59 %) of men and 32 % (CI 30-35) of women in Pomerania had hypertension compared to 36 % (CI 34-38 %) and 23 % (CI 21-25 %) in KORA-2000 with some decreases since MONICA S2 und S3. Although a significantly higher prevalence was found in the north than in the south, the medical care was equally poor in both regions: 44-46 % of men and 29-31 % of women were not aware of their hypertension. Among the hypertensives, only 26-31 % of males and 44-48 % of females were being treated for hypertension, mostly with beta blockers, ACE-inhibitors, calcium antagonists, diuretics and AT(1)-antagonists, at least half being given just one of these drugs. Fewer than half of the treated hypertensives were normotensive, regardless of the antihypertensive drug group that was given. As the overall situation regarding the treatment of hypertension remains inadequate, an aggressive approach to applying the evidence-based guidelines is essential. The underlying causes of this unacceptable degree of hypertension control requires further intensive investigation.

Severe hypertension in pregnancy: Hydralazine or labetalol: A randomized clinical trial

Objective The objective was to compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in pregnancy. Study design Two hundred women with severe hypertension in pregnancy were randomized to receive hydralazine (5 mg as a slow bolus dose given intravenously, and repeated every 20 min up to a maximum of five doses) or labetalol (20-mg intravenous bolus dose followed by 40 mg if not effective within 20 min, followed by 80 mg every 20 min up to a maximum dose of 300 mg). The primary end point was successful lowering of blood pressure and maternal hypotension. Results Women were similar with respect to characteristics at randomization. No significant differences were observed for maternal hypotension or persistent severe hypertension; only two patients in the hydralazine group presented with hypotension. Palpitations ( p = 0.01) and maternal tachycardia ( p = 0.05) occurred significantly more often in patients treated with hydralazine. The main neonatal outcomes were very similar per group; however, hypotension and bradycardia were significantly more frequent in the labetalol group. There were two neonatal deaths per antihypertensive drug group. Conclusions This randomized clinical trial shows that labetalol and hydralazine fulfill the criteria required for an antihypertensive drug to treat severe hypertension in pregnancy.

The association between antihypertensive drugs and glioma

We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case–control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03–2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal.

Chromosome 2p Shows Significant Linkage to Antihypertensive Response in the British Genetics of Hypertension Study

There is a lack of consistently linked loci influencing blood pressure and hypertension status, and this may be because of genetic or phenotypic heterogeneity. We hypothesize that stratification of subjects by response to antihypertensive drug groups could be used to stringently define subsets that will have reduced genetic and etiologic heterogeneity, by partitioning contrasting mechanisms of hypertension and, thus, enhancing gene finding. We investigated the British Genetics of Hypertension Study population, which is composed of 2142 severely hypertensive white affected sibling pairs. Nonresponse to antihypertensive therapy was defined as an on-treatment blood pressure of >140/90 mm Hg or a difference between prediagnosis and on-treatment blood pressure of <20 mm Hg. Of the nonresponders, there were 89 sibling pairs (AB) who were both on antihypertensive therapy that inhibit the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II type-1 receptor blockers, or beta-blockers), and 76 sibling pairs (CD) who were both on drugs that do not (calcium channel blockers or diuretics). Nonparametric linkage analysis carried out using markers from a 10-cM genome scan and additional "grid tightening" markers showed significant linkage in the AB group on chromosome 2p (logarithm of odds=4.84 at 90.68 Kosambi cM) and suggestive linkage for the CD group on chromosome 10q (logarithm of odds=2.83 at 125.96 Kosambi cM). The AB linkage locus attained genomewide significance after simulation using 10,000 replicates (P=0.005). This locus may contain a gene for the salt-sensitive form of hypertension and/or a pharmacogenetic locus affecting drug response. We have demonstrated for the first time identification of a significant locus by partitioning different pathways of hypertension using drug response.

Cutaneous reactions due to antihypertensive drugs

Out of a total of 1147 patients on antihypertensive drugs, 23 (2.04%) developed adverse cutaneous drug reactions (ACDR). The commonest antihypertensive drug group causing ACDR was beta-blockers of which atenolol was the commonest culprit. The second most common group was calcium channel blockers with amlodipine as the commonest offender. The most common patterns of ACDR observed included urticaria followed by lichenoid drug eruption (LDE). We noted 2 new patterns of reactions; (i) one patient developed brownish blue pigmentation of nails while on atenolol for 3 years, which resolved in 4 months after withdrawal and (ii) another patient on amlodipine for 8 years developed Schamberg's like purpuric pigmentation, which resolved on withdrawal of drug within 3 months. These findings have not been reported in the literature earlier. This study is presented for paucity of Indian data on ACDR due to antihypertensive drugs, and remarkable advancement in area of cardiovascular and antihypertensive pharmacology and a large number of population taking antihypertensive drugs.

Use of recombinant human erythropoietin in kidney transplant patients with stable graft function

The purpose of this work was to determine the necessity for rhuEPO for 50 kidney transplant patients with stable graft function. We analyzed the red cell series, blood pressure, renal function, anthropometric data of the donor and recipient, proteinuria, and relationship with other factors, including immunosuppressants, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The patients were divided into three groups depending on renal function: group A (with plasma creatinine <150 μmol/L), group B (151–250 μmol/L), and group C (>250 μmol/L). All patients were studied for 1 year. Erythropoietin use did not affect renal function, proteinuria or number of antihypertensive drugs group. The degree of renal dysfunction determined the time necessary to reach an adequate hemoglobin level (>12 g/L) and and the mean dose of weekly rhuEPO needed. The use of ACE inhibitors or ARBs increased the rhuEPO requirements in each group.

Ultrasonographic and pathological endometrial findings in asymptomatic postmenopausal women taking antihypertensive drugs

Objectives: To assess whether abnormal sonographic endometrial findings are more frequent in asymptomatic postmenopausal women receiving anti-hypertensive drugs than in normotensive women. Methods: A prospective study on 187 postmenopausal asymptomatic normotensive (group A) and 182 postmenopausal asymptomatic women receiving anti-hypertensive drugs (group B) was performed. All patients were evaluated initially by transvaginal ultrasound and endometrial sampling (Pipelle device). Those women with abnormal sonographic findings (endometrial thickness ≥5 mm or heterogeneous echogenicity) or abnormal endometrial sampling results underwent hysteroscopy and guided biopsy. Results: Patients in group B had significantly higher percentage of endometrial thickness ≥5 mm (26.9 vs. 12.8%, P<0.001) and heterogeneous endometria (23.1 vs. 12.8%, P<0.001) than in group A. Patients in group B had a significantly higher incidence of endometrial polyps (17.6 vs. 9.6%, P<0.001) too. These findings were not associated with the type of anti-hypertensive drug taken and were independent of the body mass index. Conclusions: Postmenopausal hypertensive asymptomatic women receiving pharmacological anti-hypertensive therapy show a higher percentage of abnormal sonographic endometrial findings than normotensive women.

Clinical Efficacies of Antihypertensive Drugs

Objective—According to published data, the ability to prevent various hypertension-related events differs between the various antihypertensive drug groups. Although absolute drug effects differ among studies, relative drug effects could be considered constant. We therefore explored the possibility of drawing statistically valid conclusions about the differences in clinical efficacy between various drug groups by doing an overview of published data.Design—We made a meta-analysis with a Bayesian fixed effect model in which we related the drug effects to the effects of placebo drugs. We selected 27 clinical trials from the literature according to specific criteria, including results from studies reporting the effects of the newer drugs when tested against diuretics and, β-blockers, and from studies in which diuretics and, β-blockers had been tested against placebo. We calculated the posterior probability distributions of the relative effects of angiotensin-converting enzyme (ACE) inhibitors vs calcium antagonists with three different endpoints: stroke, coronary disease and heart failure with point estimates of effects and with 95% credibility intervals. As an intermediate step in this procedure we obtained similar information about the effects of the three groups of active drugs, ACE inhibitors, calcium antagonists and diuretics or, β-blockers, tested against placebo. For coronary disease we also tested calcium antagonists against diuretics or, β-blockers.Results—ACE inhibitors and calcium antagonists have an almost identical ability to prevent stroke in hypertensive individuals with a risk ratio (RR) of 1.04. On the other hand, calcium antagonists reduce coronary disease by only 8% relative to placebo. When ACE inhibitors and calcium antagonists are compared with the Bayesian method, the outcome is a 14% difference in favor of the ACE inhibitors to prevent coronary disease, with a credibility interval almost reaching identity. Nor do calcium antagonists do as well as diuretics or, β-blockers in this respect, RR = 1.12 with 95% credibility interval 1.01-1.24. All the tested drug groups have a profound preventive effect on the occurrence of heart failure when given to hypertensive patients, showing reductions of 42-54%. When ACE inhibitors are compared with calcium antagonists RR = 0.79, with a credibility interval 0.65-0.95.Conclusion—There is statistically an indisputable difference between ACE inhibitors and calcium antagonists in respect of effects on coronary disease and heart failure when treating hypertensive individuals, ACE inhibitors being more efficacious. There are no differences in the effect on stroke. Moreover, ,β-blockers or diuretics are also superior to calcium antagonists in preventing coronary events.

Long-term Protection in At-risk Hypertensive Patients - A Role for Nifedipine GITS?

Hypertensive patients who are at high risk of developing cardiovascular (CV) complications have become the focus of modern treatment guidelines. The choice of antihypertensive therapies in these patients should be evidence-based: in particular, there should be evidence of a beneficial impact on CV events in addition to blood pressure-lowering effects. The International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) is the first, large, randomized, double-blind study undertaken exclusively in high-risk hypertensive patients, with CV events as a prospectively defined primary end-point. The choice of a diuretic (co-amilozide) as a comparator reflects the fact that this group of antihypertensive drugs has been shown to reduce CV events in high-risk hypertensive patients. Nifedipine, administered in a long-acting gastrointestinal-transport-system (GITS) formulation, and coamilozide were equally effective in preventing overall CV or cerebrovascular complications. This finding extended to the subgroup of patients with diabetes at baseline. Substudies to INSIGHT showed that, compared with co-amilozide, nifedipine GITS was significantly more effective at preventing an increase in intima-media thickness in the carotid artery and significantly slowed the progression of coronary calcification. The results from INSIGHT support incorporating nifedipine GITS in the management of high-risk hypertensive patients to prevent atherosclerosis-related illness and death.

Is resistant hypertension really resistant?

Background Managing resistant hypertension is difficult and mostly involves expensive testing seeking an underlying secondary cause. This study was undertaken to determine 1) the extent of the white-coat phenomenon in patients with resistant hypertension, and 2) whether 24-h ambulatory blood pressure (BP) monitoring (ABPM) or having BP recorded by a nurse instead of the referring doctor could clarify how many apparently resistant hypertensives actually have controlled BP. Methods This study involved 611 patients with BP ≥140/90 mm Hg who were referred for 24-h ABPM by their specialist or general practitioner, including 277 patients who were taking no antihypertensives (group 1), 216 taking one or two antihypertensive drugs (group 2), and 118 taking at least three antihypertensives in combination (group 3). Each had BP recorded by one of two nurses before 24-h ABPM. Controlled BP was defined as awake ambulatory BP <135/85 mm Hg and the white-coat effect was the difference between the BP recorded by the referring doctor or nurse and the average awake ambulatory BP. Results: Those with resistant hypertension (group 3) were older (61 years (12) v group 1: 46 years (14) and group 2: 56 (14) years; P < .001), but were of similar weight, height, and arm circumference to the other groups. Referral systolic, but not diastolic BP was higher in resistant hypertensives (mean 171/95 v 154/95 mm Hg and 164/94 mm Hg, respectively, P < .001 for systolic BP only). Twenty-eight percent of resistant hypertensives and 32% of those taking no antihypertensive drugs had normal awake ambulatory BP and the white-coat effect attributable to the referring doctor was always greater than that due to the nurse (range 16 to 26/12 to 14 mm Hg v 9 to 17/4 mm Hg, P < .001). Nurse recorded BP was highly sensitive (97%) in identifying awake hypertension but lacked specificity (57%) to replace ABPM. Conclusion Our results show that approximately one in four patients with apparent resistant hypertension referred for ABPM have controlled BP and one-third of patients referred for initial evaluation of office or clinic hypertension have normal BP using ABPM, ie, white-coat hypertension. Twenty-four-hour ABPM appears an appropriate initial step before further investigating or treating patients with apparently resistant hypertension.

Chronic beta-blocker therapy improves outcome and reduces treatment costs in chronic type B aortic dissection.

To compare the medical treatment of chronic type B aortic dissection with beta-blockers versus other antihypertensive treatments in terms of their requirement for surgical intervention and treatment costs. Case records of the 130 patients treated for aortic dissection type B in this unit between 1988 and 1997 were reviewed. Seventy-eight of 130 patients with chronic dissection have received isolated medical treatment. Seventy-one of 78 patients were discharged alive. Fifty-one of 71 received beta-blocker treatment, 20/71 were treated with other antihypertensive drugs. Surgery for aortic dissection became necessary in 20/71 patients (28%) during follow-up (mean, 4.2 years): 10/51 in the beta-blocker group and 9/20 in the other antihypertensive drug group. The freedom from subsequent aortic operation was 80 and 47%, respectively (P=0.001). Indications for emergency surgery were increased aortic diameter (79%), symptomatic aortic aneurysm (11%), and renal artery hypoperfusion (5%). The median hospitalization time during follow-up (dissection-related) was 2 days for patients who received beta-blockers and 16 days for patients who received other antihypertensive drug treatments (P=0.001). The cost of treatment/patient per year amounted to 644 and 12748 euros, respectively. A substantial proportion of patients with chronic type B dissection who receive initial medical management will later need surgery. Long-term treatment with beta-blockers reduces the progression of aortic dilatation, the incidence of subsequent hospital admissions, as well as the incidence of late dissection-related aortic procedures and the cost of treatment. Patients with chronic type B dissection need, in addition to frequent follow-up of aortic diameter, continuous treatment with beta-blocking agents.

Ace inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension

The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; β-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. β-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on β-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = β-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP ( P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on β-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. β-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.

IS RESISTANT HYPERTENSION TRULY RESISTANT?

Objectives (1) to compare the magnitude of the white‐coat effect in patients with mild and resistant hypertension and (2) to determine the prevalence of controlled BP in patients with ‘resistant’ hypertension.Methods Referring doctors' BP was compared with awake and 24 hour ambulatory BP monitor (ABPM) BP in 922 hypertensive patients referred for ABPM by their general practitioners (42%) or specialists (58%). 432 were taking no antihypertensives at the time of their ABPM study (Group 0), 336 were taking 1‐2 antihypertensive drugs (Group 1) and 154 were taking ≥ 3 antihypertensive drugs (Group 2 ‐ resistant hypertension). Controlled BP was defined as awake ABPM BP &lt; 135/85mmHg.Results Patients with resistant hypertension were significantly older (60 ± 13 yrs) than group 0 (44 ± 15 yrs) and group 1 (55 ± 14 yrs) patients (p &lt; 0.001) but were of similar weight, height and upper arm circumference. The difference between referral BP and awake ABPM BP, the white‐coat effect (WCE), increased significantly across the groups (15/9 vs 26/14 vs 29/15 mmHg, p &lt; 0.005). 34% of group 0 patients had normal ABPM BP, ie. white‐coat hypertension, while 34% of group 1 and 26% of group 2 patients had controlled BP by ABPM criteria.Conclusion Approximately 1 in 3 of this selected cohort exhibited white coat hypertension and 1 in 4 of those with apparent resistant hypertension had well controlled BP when assessed by 24 hour ABPM. ABPM appears an appropriate initial step in the investigation of both mild hypertension and apparent drug resistant hypertension, thereby reducing unnecessary drug treatment and investigations for secondary causes of hypertension in these patients.

IS RESISTANT HYPERTENSION TRULY RESISTANT?

Objectives (1) to compare the magnitude of the white‐coat effect in patients with mild and resistant hypertension and (2) to determine the prevalence of controlled BP in patients with ‘resistant’ hypertension.Methods Referring doctors' BP was compared with awake and 24 hour ambulatory BP monitor (ABPM) BP in 922 hypertensive patients referred for ABPM by their general practitioners (42%) or specialists (58%). 432 were taking no antihypertensives at the time of their ABPM study (Group 0), 336 were taking 1‐2 antihypertensive drugs (Group 1) and 154 were taking ≥ 3 antihypertensive drugs (Group 2 ‐ resistant hypertension). Controlled BP was defined as awake ABPM BP &lt; 135/85mmHg.Results Patients with resistant hypertension were significantly older (60 ± 13 yrs) than group 0 (44 ± 15 yrs) and group 1 (55 ± 14 yrs) patients (p &lt; 0.001) but were of similar weight, height and upper arm circumference. The difference between referral BP and awake ABPM BP, the white‐coat effect (WCE), increased significantly across the groups (15/9 vs 26/14 vs 29/15 mmHg, p &lt; 0.005). 34% of group 0 patients had normal ABPM BP, ie. white‐coat hypertension, while 34% of group 1 and 26% of group 2 patients had controlled BP by ABPM criteria.Conclusion Approximately 1 in 3 of this selected cohort exhibited white coat hypertension and 1 in 4 of those with apparent resistant hypertension had well controlled BP when assessed by 24 hour ABPM. ABPM appears an appropriate initial step in the investigation of both mild hypertension and apparent drug resistant hypertension, thereby reducing unnecessary drug treatment and investigations for secondary causes of hypertension in these patients.

New approaches to the uses of beta blocking drugs in hypertension.

After a slow start, beta-blockers have become widely used as first-line agents in the treatment of hypertension, and recommended as such in recently published guidelines. There is evidence that the beta1-selective agents are more efficacious than non-selective blockers that inhibit both beta1 and beta2 receptors. Notwithstanding some earlier evidence to the contrary, it appears that beta1-selective drugs are equi-effective in young and elderly whites, younger, ie, under mid 60s, blacks. It is with the combination of age and being black that beta-blockers are usually less useful than some other groups of antihypertensive drugs, most notably calcium antagonists and diuretics. Primary prevention studies indicate beta-blockers reduce the incidence of cerebro-vascular disease and coronary heart disease in younger patients but they appear less effective than diuretics in the elderly. Beta-blockers are particularly indicated in patients who have experienced a myocardial infarction where they are often under used. There is some evidence that even in post-infarction patients with co-existent chronic obstructive airways disease, usually regarded as a contra-indication, experience an improved 2-year survival with the use of beta-blockers. Recently they have also been demonstrated to improve prognosis in heart failure patients, previously regarded as a contra-indication. Likewise, recent studies have shown that atenolol was at least as effective as captopril in improving the outlook in hypertensive patients with non-insulin dependent diabetes. While earlier comparisons with the non-selective lipid soluble propranolol indicated otherwise, comparisons with beta1-selective agents have indicated a similar effect on quality of life assessments with angiotensin-converting enzyme inhibitors.

Efficacy of celiprolol in the treatment of hypertension in the elderly: An open-label study

Abstract Objective An open-label, multicenter trial was conducted to investigate the efficacy and safety profiles of celiprolol, a beta 1 -receptor selective beta-blocker with intrinsic beta 2 -receptor selective sympathomimetic activity, in the long-term treatment of elderly patients with hypertension. Methods Celiprolol was administered to 101 patients ≥60 years of age with essential hypertension; previously untreated patients were given celiprolol alone (group A), and previously treated patients were given celiprolol in addition to other antihypertensive drugs (group B). Results During the treatment period, 6 patients in group A and 5 in group B dropped out, mainly because they transferred to another medical institution or were not available for measurements. Baseline blood pressure was 169.7 ± 1.7/95.4 ± 1.0 mm Hg (n = 41) in group A and 172.1 ± 2.3/94.7 ± 1.6 mm Hg (n = 49) in group B. One year later, blood pressure was stable at 147.3 ± 2.1/83.5 ± 1.6 mm Hg (n = 35) and 140.5 ± 2.2/80.8 ± 1.6 mm Hg (n = 44), respectively. Baseline pulse rate was 77.2 ± 1.7 beats/mill in group A and 78.1 ± 2.2 beats/min in group B. One year later, the pulse rate was 70.4 ± 1.5 beats/min and 69.5 ± 1.8 beats/min, respectively. Patients with baseline total cholesterol ≥220 mg/dL (n = 36), those with triglycerides ≥150 mg/dL (n = 35), and those with low-density lipoprotein cholesterol ≥150 mg/dL (n = 13) showed a significant reduction 1 year later. No significant changes were observed among patients with high-density lipoprotein cholesterol levels Conclusions A stable antihypertensive effect was observed after long-term administration of celiprolol in elderly patients with hypertension. The drug was also shown to have a beneficial effect on serum lipids.

α-Blockers in Hypertension

SummaryHypertension is a heterogeneous disease and this is reflected in the marked variability in response to monotherapy. Co-administering antihypertensive therapies has several theoretical benefits, namely enhanced efficacy, improved tolerability, increased compliance and, in some cases, potentially beneficial changes in biochemical variables associated with increased cardiovascular risk, such as improvements in lipid profiles. α1-Blockers, such as doxazosin, have several favourable properties which should be advantageous when used with other agents. Their mechanism of action is complementary to that of each of the other four main groups of antihypertensive drugs and, in each case, enhanced efficacy has been observed when α1-blockade has been added to monotherapy with other drug classes. Synergistic effects have been seen when an α1-blocker is administered together with either a calcium channel blocker or angiotensin-converting enzyme inhibitor. While α1-blockers induce regression of left ventricular hypertrophy, the possibility of enhanced effects during multiple therapy has not been explored, α1-Blockers exert positive effects on lipids (limited data suggest that they are able to reverse the deleterious lipid effects of diuretics and β-blockers) and exert neutral or positive effects on glucose homeostasis. Further studies are needed to determine whether α1-blockers can alleviate the adverse effects of β-blockers or diuretics on glucose homeostasis, α1-Blockers, when given concomitantly with other antihypertensive drugs, are well tolerated, conferring advantages with respect to patient compliance. The current data favour the use of α1-blockers as an additional component of antihypertensive therapy, but further studies are needed to address the metabolic and end-organ effects of such treatment regimens.

Treatment guidelines in hypertension: current limitations and future solutions

Among the many guidelines and recommendations put forward by national and international authorities in recent years, there has been close agreement that the physician should assess each patient carefully over many months, should address the total profile of cardiovascular risk not just the raised blood pressure, and should treat patients right up to the age of 85 years with either classical essential hypertension or isolated systolic hypertension. The major guidelines described five groups of first-line antihypertensive drugs: diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium antagonists and alpha-blockers. In other areas, the various guidelines were either united in uncertainty, or divided on the best course of action. The availability of many new methods and approaches for the measurement of blood pressure has introduced greater uncertainty into the interpretation of the blood pressure level in the individual patient, with question marks still surrounding the interpretation of white-coat hypertension, of ambulatory blood pressure monitoring and of home blood pressure readings in relation to clinic blood pressure. There is lack of uniformity in recommendations for the threshold values at which raised blood pressure should be lowered and in the recommendations for the target blood pressure the physician should set in the individual patient. Since the publication of the major guidelines in 1993 and 1994, the greatest uncertainty has surrounded the choice of drugs to initiate treatment. This reflects the fact that so far no major trials have been completed confirming that the newer agents such as ACE inhibitors, calcium antagonists or alpha-blockers reduce cardiovascular morbidity and mortality in hypertensive patients. While awaiting the results of the many prospective randomized trials that are in progress with these newer agents, a number of case-control studies have raised concerns that non-potassium-sparing diuretics may increase the incidence of sudden cardiac death and that calcium antagonists might increase the occurrence of coronary heart disease in hypertensive subjects. These issues highlight the importance of initiating prospective, randomized, controlled trials early in the development of all new drugs. While awaiting the results of trials currently in progress, the physician should continue to use all five groups of antihypertensive drugs, tailoring the choice of drug to suit the individual patient, and should use low doses of antihypertensive drugs either alone, or in appropriate combinations.