Neurobehavioral effects of antihypertensive medications.

Although millions of hypertensive individuals receive chronic treatment with antihypertensive medication, the effect on the central nervous system by these drugs is poorly understood. Such treatment, while generally well tolerated, frequently produces symptoms of drowsiness, weakness, altered memory and impaired concentration. In addition to subjective evidence derived from patient reports, a large number of investigations have now been published which attempt to objectively assess the influence of antihypertensive medication on behavioral or cognitive performance. This paper summarizes and critically evaluates experimental studies of the effect of antihypertensive medication on subjects' performance of neuropsychological tasks and reviews the pharmacologic mechanisms by which these drugs may affect behavior. The literature is incomplete in its assessment of all domains of neuropsychological performance and all drug classes, and methodologic deficiencies are common. Nonetheless, the consensus of all studies and the findings of well-designed studies in particular do not identify any notable areas of performance impairment in patients receiving antihypertensive medication. Moreover, results suggest that, in certain instances, drug treatment may even enhance performance. In light of the limitations of the literature, however, an adequate understanding of the effects of antihypertensive therapy on behavioral functioning awaits completion of large, well-designed investigations including all major drug classes and thorough neurobehavioral assessments.     

Analysis of integrated clinical safety data of tadalafil in patients receiving concomitant antihypertensive medications

This pooled safety analysis assessed the incidence of hypotension‐related treatment‐emergent adverse events (TEAEs) and major adverse cardiovascular events (MACEs) in patients with concomitant use of tadalafil and antihypertensive medications. Data were pooled from seventy‐two Phase II–IV studies conducted on patients with a diagnosis of erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH). Studies were categorized as either All placebo‐controlled studies or All studies. The incidences of hypotension‐related TEAEs and MACEs were analyzed by indication; by use of concomitant antihypertensive medications; and by the number of concomitant antihypertensive medications. A total of 15 030 and 22 825 patients were included in the analyses for All placebo‐controlled studies and All studies, respectively. In the All placebo‐controlled studies, the incidence of hypotension‐related TEAEs and MACEs was ranging between 0.6–1.5% and 0.0–1.0%, respectively, across all indications. Tadalafil was associated with an increase in hypotension‐related TEAEs only in the ED as‐needed group not receiving any concomitant antihypertensive medications (p‐value = .0070); no significant difference was reported between placebo and tadalafil in the groups of patients receiving ≥1 antihypertensive medication (p‐values ≥ .7386). Similarly, no significant differences (p‐values≥ .2238) were observed in the incidence of MACEs between tadalafil and placebo treatment groups, with or without concomitant use of antihypertensive medications, and across all indication categories. In the All studies group, results were similar. The pooled analysis showed no evidence that taking tadalafil alongside antihypertensive medications increases the risk of hypotension‐related TEAEs or MACEs compared with antihypertensive medications alone.     

Losartan vs. amlodipine treatment in elderly oncologic hypertensive patients: A randomized clinical trial

Elderly neoplastic patients frequently may show hypertension and hyperuricemia, before and after chemotherapeutic treatments. The purpose of this study was to evaluate the efficacy of losartan which is an antihypertensive drug with uricosuric properties vs. amlodipine in hypertensive neoplastic elderly patients. This was an open-labeled, randomized, comparative trial. The study was performed as a 30-day study. Seventy patients with cancer were randomly assigned to receive losartan or amlodipine. Blood pressure (BP), blood urea nitrogen (BUN) levels, creatinine, serum and urinary uric acid, creatinine and uric acid clearance were determined before and after chemotherapy. One day after chemotherapy in losartan group vs. amlodipine group we observed a significant difference in urinary uric acid (p < 0.001) of 18 mg/24 h vs. 40 mg/24 h. Thirty days after chemotherapy we observed a significant difference in azotemia of 0.0 mg/dl vs. 3.8 mg/dl (p < 0.001), serum uric acid of 0.05 mg/dl vs. 0.49 mg/dl (p < 0.001), urinary uric acid (p < 0.001) of 23 mg/24 h vs. 0.0 mg/24 h, GFR of 2 ml/min/1.73 m² vs. −8 ml/min/1.73 m² (p < 0.05) and systolic BP (SBP) of 3.6 mmHg vs. 0.8 mmHg (p < 0.05). The findings of the present study support the effective role of losartan compared to amlodipine in treating hypertension and hyperuricemia in elderly patients under chemotherapeutic treatment.     

A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: effect on antihypertensive drug requirement in clinical practice.

The effect of a low sodium, low fat, high fibre diet in allowing a reduction of antihypertensive medication was compared with the effect produced by the individual components of this diet in an observer-blind controlled trial using 196 patients with essential hypertension. Patients were followed up 1.5 months after the last change in medication. In the control group a 33% reduction in medication was possible, with 24% of patients off medication altogether. The low fat, high fibre and low sodium groups showed larger reductions in medication (38%, 47% and 45% respectively), but not significant compared with the control group. The combination group had the largest and highly significant medication reduction (64%), and significantly more patients stopped medication (57.5%), compared with the control group. Since compliance assessment closely corresponded to normal clinical practice these results should represent what is possible in routine clinical practice. This is of importance as drug treatment has side effects, and may be associated with increased cardiovascular risk not found with dietary alternatives.     

Mega clinical trial of calcium channel antagonist in hypertensive patients

Recent mega-clinical trials of calcium channel antagonists in hypertensive patients revealed that treatment with calcium channel antagonists reduced the incidence of cardiovascular events of hypertensive patients compared with placebo. Additionally, it has been demonstrated that compared with diuretics or beta-blockers, treatment with calcium channel antagonists reduced the incidence of stroke. However, compared with diuretics or beta-blockers, treatment with calcium channel antagonists has been demonstrated to increased the occurrence of coronary heart disease and heart failure in hypertensive patients. Nevertheless, it is well known that sufficient blood pressure lowering therapy reduced the incidence of cardiovascular events in hypertensive patients. From this point of view, calcium channel antagonists seem to be necessary for the treatment of hypertension.     

Self-reported side effects from antihypertensive drugs. A clinical trial. Quality of Life Research Group

We report on the distress associated with physical symptoms in 761 male hypertensive patients enrolled in a clinical trial of the effects of captopril, methyldopa or propranolol on quality of life. Educational level at entry into the trial showed a negative association with a series of physical symptom distress items among patients not previously treated with antihypertensive medications but no association with symptoms among the previously treated. Over the 24 weeks of therapy captopril as monotherapy was associated with no change from baseline in distress in all symptoms examined. In contrast, distress increased in the methyldopa treated patients for dry mouth and blurred vision. Propranolol treated patients had increased "trouble getting breath," bradycardia, shortness of breath or wheezing, and blurred vision. Between group comparisons revealed significant differences favorably comparing captopril to both methyldopa and propranolol in regard to fatigue, and blurred vision, as well as to methyldopa alone for dry mouth and "feeling worn out." There were significant differences as well between captopril and propranolol with patients on propranolol worsening in bradycardia. Other comparisons of patients on propranolol and methyldopa monotherapy showed propranolol patients worsening in bradycardia and loss of taste, but methyldopa patients reported more dry mouth and feeling worn out than those on propranolol. The addition of hydrochlorothiazide to therapy worsened total physical symptom distress scores for methyldopa and propranolol patients. This study confirms the value of methods which assess the degree of distress associated with symptoms commonly reported by hypertensive patients receiving antihypertensive medications. This approach can be useful in establishing a treatment regimen least likely to cause distress and can be of value in preserving quality of life, preventing noncompliance, and withdrawal from treatment.     

Nonadherence to antihypertensive medications amongst patients with uncontrolled hypertension: A retrospective study

Medication nonadherence represents a modifiable risk factor for patients with hypertension. Identification of nonadherent patients could have significant clinical and economic implications in the management of uncontrolled hypertension.We analysed the results of 174 urinary adherence screens from patients referred to Addenbrooke''s Hospital, Cambridge, for uncontrolled hypertension. Cases were identified for evaluation by results of liquid chromatography-tandem mass spectrometry of urine samples (males: 91; females: 83; age range: 17–87). We performed a binary logistic regression analysis for nonadherence using age, sex, and number of medications prescribed (both antihypertensives and non-antihypertensives separately) as independent predictors. Rates of nonadherence for individual antihypertensive drugs were calculated if prescribed to ≥10 patients.The overall rate of nonadherence to one or more prescribed antihypertensive medications was 40.3%. 14.4% of all patients were nonadherent to all prescribed antihypertensive medications (complete nonadherence), whereas 25.9% of all patients were nonadherent to at least 1, (but not all) prescribed antihypertensive medications (partial nonadherence). 72% of patients were prescribed ≥3 antihypertensives And for every increase in the number of antihypertensive medications prescribed, nonadherence increased with adjusted odds ratios of 2.9 (P < .001). Logistic regression showed that women were 3.3 times more likely to be nonadherent (P = .004). Polypharmacy (≥6 medications prescribed for hypertension and/or concomitant comorbidities) was prevalent in 52%. Bendroflumethiazide and chlortalidone demonstrated the highest and lowest nonadherences respectively (45.5% and 11.8%).Rate of nonadherence in patients with hypertension was significantly impacted by sex and number of antihypertensive medications prescribed. Understanding these factors is crucial in identifying and managing nonadherence.     

Safety and blood pressure trajectory of short-term withdrawal of antihypertensive medications in older adults: Experience from a clinical trial sample

BackgroundThe short-term safety of and blood pressure changes after withdrawing hypertension treatment in older adults in preparation for clinical trials have not been well established.MethodsParticipants were enrolled in a clinical trial and antihypertensive medications were tapered over 3 weeks (week 1: reduction by 25%–50%; week 2: 50%–75%, week 3: off). Blood pressure was measured at the initial visit and after stopping all antihypertensive therapy (personnel) and twice a day during the taper phase (provided monitor). Trend analyses and linear models were used to assess changes in blood pressure.ResultsAll participants (n = 53, mean age = 71 years, total of 1158 readings) successfully tapered their medications with no symptoms. Only 2% of the readings exceeded 180/100 mm Hg, but none were consecutive. Blood pressure gradually increased with an overall increase of 12/6 mm Hg, 95% confidence interval (4/1, 21/11). The daily increase in blood pressure was 0.2 mm Hg (standard error = 0.1) in both the systolic and diastolic blood pressure. Increases in systolic and diastolic blood pressure were comparable for all antihypertensive classes (P > .05 for all).ConclusionShort-term (<3-4 weeks) withdrawal of antihypertensive therapy in older adults with hypertension is safe and is associated with mild increases in blood pressure.     

Adherence to antihypertensive medications among adult hypertensive patients attending chronic follow-up units of Dessie Referral Hospital,Northeastern Ethiopia: A cross-sectional study

Hypertension is the leading cause of increased morbidity and mortality rates worldwide. Despite adherence to therapies is the important determinant of treatment success to reduce apparent resistant hypertension, maintaining good adherence to antihypertensive medications remained the most serious challenge. Thus, this study aimed to assess adherence to antihypertensive medications among adult hypertensive patients in Dessie Referral Hospital.A cross-sectional study design was conducted among hypertensive patients during May and June 2020. The study participants were selected using a systematic random sampling technique. The collected data were entered into EpiData version 4.4 and exported to SPSS version 25.0 software for data cleaning and analysis. Data were analyzed using bivariable and multivariable logistic regression at a 95% confidence interval (CI). A variable that has a P-value < .05 was declared as statistically significant. Hosmer–Lemeshow test was used to test goodness-of-fit and multicollinearity was tested.The overall good adherence to antihypertensive medications was 51.9%; 95% CI: (46.8–58.3%) and poor adherence was 48.1%. Factors associated with good adherence were: sex—female adjusted odd ratio (AOR) = 1.31; 95% CI (1.06–2.52), occupational status-employed AOR = 2.24; 95% CI (1.33–3.72), good knowledge of the disease AOR = 2.20; 95% CI (1.34–3.72) and good self-efficacy AOR = 1.38; 95% CI (1.20–2.13).This study revealed that almost half of the hypertensive patients in Dessie Referral Hospital had good antihypertensive medication adherence. Sex, occupational status, knowledge, and self-efficacy were factors associated with good adherence. Therefore, health education should be given to patients on the importance of complying with medication and patients should be monitored by health extension workers.     

Association of optimal blood pressure with mortality in patients taking antihypertensive medications

We investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007‐2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30‐74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan‐Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all‐cause mortality according to SBP and/or DBP, we calculated Harrell''s concordance‐index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell''s C‐indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients.     

Type A behavior and psychological characteristics of hypertensive patients undergoing antihypertensive treatment

The aim of this study was to evaluate the presence of "type A" behaviour and possible psychological distress in 373 hypertensive patients. One-hundred and ninety-five males, 56.2 +/- 6.2 years old and one-hundred and seventy-eight females, 57.1 +/- 6.2 years old, coming from the IPPPSH and still under double-blind treatment with or without a beta-blocker (oxprenolol 160 mg SR), were studied by means of the Jenkins Activity Survey form C and several tests from the Cognitive Behavioural Assessment Battery (CBA-2.0). Seventy-four point eight percent of the patients showed a "type A" pattern, and 25.5% were in the extreme predictive interval for coronary heart disease according to WCGS. "Type A" pattern was not influenced by variables such as age, sex, education, job or previous pharmacological treatment. The patients studied did not show any particular psychological distress at the psychometric evaluation. However, special social and cultural characteristics and different therapies influenced some symptoms, such as anxiety, depression and somatic lamentation. According to this study: "type A" behaviour seems to be a steady feature of the hypertensive patient; furthermore, it seems to be due to a "biological imprinting" which can be considered a cause of hypertension; psychological distress depends on a particular set of environmental stimuli. In the first case an accurate prevention is needed while, in the second case adequate pharmacological and/or psychological therapies are needed.     

Pravastatin decreases blood pressure in hypertensive and hypercholesterolemic patients receiving antihypertensive treatment.

BACKGROUND: Previous studies have suggested that the lipid-lowering agents, statins, may help reduce blood pressure (BP). The goal of the present study was to characterize the effect of pravastatin on BP in hypercholesterolemic and hypertensive patients already receiving antihypertensive drugs. METHODS AND RESULTS: Eighty-two patients with hypercholesterolemia were retrospectively studied before and after 3 months of treatment with pravastatin. Forty-four patients had hypertension (HT group) and were receiving antihypertensive treatment, while the remaining 38 patients were normotensive (NT group). Patients in the HT group were further subdivided into those with uncontrolled or controlled BP. Pravastatin treatment significantly reduced systolic BP (SBP) in the HT group (134+/-16 to 130+/-13 mmHg, p<0.005) but not in the NT group (124+/-10 to 123+/-9 mmHg, p=0.52), despite the fact that treatment significantly reduced low-density lipoprotein cholesterol in both groups (HT group 178+/-27 to 132+/-17 mg/dl, p<0.0001; NT group 169+/-27 to 125+/-21 mg/dl, p<0.0001). Further, pravastatin significantly decreased SBP in the uncontrolled BP group (148+/-7 to 138+/-12 mmHg, p<0.005) but not in the controlled BP group (122+/-10 to 123+/-9 mmHg, p=0.72). CONCLUSION: Concomitant use of statins and antihypertensive drugs could result in improved BP control in hypertensive patients with hypercholesterolemia.     

抗高血压药物的选择

国内外几个重要的高血压治疗指南(指南)将利尿剂、β-受体阻滞剂、钙通道阻滞剂(CCB)、血管紧张素转换酶抑制剂(ACEI)、血管紧张素Ⅱ受体拮抗剂(ARB)以及α-受体阻滞剂作为一线抗高血压药物。六大类抗高血压药物的广泛应用，使高血压治疗及控制状况得到改观，大大降低了全球心血管病发生和死亡的危险。但目前如何正确选择及合理使用抗高血压药物，更大程度地使高血压患者从抗高血压药物治疗中获益，是我们今后面临的重要任务之一。     

Response to six classes of antihypertensive medications by body mass index in a randomized controlled trial

Blood pressure increases with increasing body mass index (BMI) and BMI is linearly related to blood pressure in population studies. Obesity has been said to cause resistance to antihypertensive medications. We compared short-term and 1-year blood pressure response by BMI category and weight change with hydrochlorothiazide, atenolol, diltiazem-SR, captopril, clonidine, prazosin, or placebo in 1292 male veterans. Drug doses were titrated to achieve goal diastolic blood pressure <90 mm Hg over 4–8 weeks. Patients who achieved goal blood pressure were maintained for 1 year. BMI did not predict change in systolic, diastolic or pulse pressures during titration for any drug. At 1 year obese patients (BMI >30) were 2.5 times more likely to have diastolic blood pressure controlled by atenolol than normal weight (BMI <27) patients ( p =0.01). Only prazosin patients gained weight: 1.7 lb (end-titration ,p <0.0001; 1-year , p =0.02). Obesity does not appear to cause resistance to antihypertensive medications.     

Sexual dysfunction in hypertensive patients treated with losartan

BACKGROUND: Impaired erectile function in men is a component of the dysmetabolic syndrome of high blood pressure as well as a sequela of antihypertensive therapy. This prospective interventional study in men with uncontrolled hypertension (blood pressure > or =140/90 mm Hg) used a survey instrument to assay sexual dysfunction before and after therapy with losartan. METHODS: We evaluated the influence of a 12-week therapy with losartan in 82 hypertensive subjects with (n = 82) and without (n = 82) a diagnosis of erectile dysfunction using a self-administered questionnaire validated in another 60 subjects with hypertension. RESULTS: From an initial sample of 323 hypertensive men and women, 82 men, aged 30 to 65 years, with sexual dysfunction underwent a 12-week regimen of losartan therapy (50-100 mg/day). Losartan treatment improved sexual satisfaction from an initial 7.3 to 58.5% (chi2; P = 0.001). Subjects reporting a high frequency of sexual activity improved from 40.5% initially to 62.3% after drug treatment, whereas the number of patients with low or very low frequency of sexual activity decreased significantly (chi2; P = 0.001). At the completion of the 12-week losartan regimen, only 11.8% of the treated subjects reported in improvement in sexual function. Improvement on quality of life was demonstrated in 73.7% of subjects medicated with losartan, 25.5% reported no changes, and only 0.8% felt worse. In the group without sexual dysfunction, losartan had a nonsignificant effect on sexual function. CONCLUSIONS: Our data suggest that losartan improved erectile function and both satisfaction and frequency of sexual activity. Because side effects are one of the most influential factors in the management of hypertension, an added benefit of losartan therapy may be its positive impact on quality of life.