The addition of doxazosin to the treatment regimen of hypertensive patients not responsive to nifedipine

The efficacy and safety of doxazosin, a selective α₁-inhibitor, were assessed in hypertensive patients who failed to respond to nifedipine. Fifty patients were entered into a study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks, all 43 efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either ≤90 mm Hg or ≥10 mm Hg reduction) at a mean daily dose of 3.1 mg. Ninety-three percent achieved blood pressure control (sitting diastolic blood pressure ≤90 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, sitting systolic and diastolic blood pressures of efficacy evaluable patients were reduced (p < 0.05) by $\text{16}\text{18}\text{mm Hg}$ from a mean baseline of $\text{157}\text{103}\text{mm Hg}$ to a final value of $\text{141}\text{85}\text{mm Hg}$. The most prevalent side effect was vertigo (six patients). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment was excellent or good for 98% of patients for both efficacy and toleration. From baseline to final visit there was a highly significant reduction of 17% (p < 0.001) in the calculated coronary heart disease risk score, which was based on the Framingham equation.     

Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study

Aims: To compare the efficacy, safety and tolerability of linagliptin or placebo administered for 24 weeks in combination with pioglitazone in patients with type 2 diabetes mellitus (T2DM) exhibiting insufficient glycaemic control (HbA1c 7.5–11.0%). Methods: Patients were randomized to receive the initial combination of 30 mg pioglitazone plus 5 mg linagliptin (n = 259) or pioglitazone plus placebo (n = 130), all once daily. The primary endpoint was change from baseline in HbA1c after 24 weeks of treatment, adjusted for baseline HbA1c and prior antidiabetes medication. Results: After 24 weeks of treatment, the adjusted mean change (±s.e.) in HbA1c with the initial combination of linagliptin plus pioglitazone was ?1.06% (±0.06), compared with ?0.56% (±0.09) for placebo plus pioglitazone. The difference in adjusted mean HbA1c in the linagliptin group compared with placebo was ?0.51% (95% confidence interval [CI] ?0.71, ?0.30; p < 0.0001). Reductions in fasting plasma glucose (FPG) were significantly greater for linagliptin plus pioglitazone than with placebo plus pioglitazone; ?1.8 and ?1.0 mmol/l, respectively, equating to a treatment difference of ?0.8 mmol/l (95% CI ?1.2, ?0.4; p < 0.0001). Patients taking linagliptin plus pioglitazone, compared with those receiving placebo plus pioglitazone, were more likely to achieve HbA1c of <7.0% (42.9 vs. 30.5%, respectively; p = 0.0051) and reduction in HbA1c of ≥0.5% (75.0 vs. 50.8%, respectively; p < 0.0001). β‐cell function, exemplified by the ratio of relative change in adjusted mean HOMA‐IR and disposition index, improved. The proportion of patients that experienced at least one adverse event was similar for both groups. Hypoglycaemic episodes (all mild) occurred in 1.2% of the linagliptin plus pioglitazone patients and none in the placebo plus pioglitazone group. Conclusion: Initial combination therapy with linagliptin plus pioglitazone was well tolerated and produced significant and clinically meaningful improvements in glycaemic control. This combination may offer a valuable additive initial treatment option for T2DM, particularly where metformin either is not well tolerated or is contraindicated, such as in patients with renal impairment.     

The effect of additional therapeutic ultrasound in patients with primary hip osteoarthritis: a randomized placebo-controlled study

To the best of our knowledge, there is no study in the English literature about the usefulness of ultrasound therapy in degenerative hip osteoarthritis. The aim of this study was to examine its short- and long-term efficacy in patients with primary hip osteoarthritis with regard to pain, functional status, and quality of life (QoL). Forty-five patients with primary hip osteoarthritis were enrolled into the study. Demographic and clinical characteristics including age, sex, duration of disease, and pain on activity and at rest using visual analogue scale (VAS) were recorded. Functional status was determined by a 15-m timed walking test and Western Ontario McMaster Osteoarthritis Questionnaire. QoL was determined by the Short Form-36 survey (SF-36). Each patient was randomly assigned to either group I (standard physical therapy including hot pack and exercise program), group II (sham ultrasound in addition to standard physical therapy), or group III (ultrasound and standard physical therapy). The main outcome measures of the treatment were pain intensity by VAS; functional status measurements that were evaluated at baseline, at the end of the therapies, and at the first and third month of follow-up; and QoL scores that were determined at baseline and at the end of the first and third months. Twelve male and 33 female patients (mean age, 65.3 ± 6.7 years; mean disease duration, 2.5 ± 1.7 years) were included in the study. There were no differences between the groups regarding demographic variables on entry to the study. There were 15 patients in each group. Pain and functional outcome measures were determined to have improved significantly in all of the groups at the end of the therapies, but these improvements continued at the end of the first and third months only in group III (p < 0.001) The physical subscores of SF-36 were improved at the end of the first month and were maintained at the end of the third month only in patients receiving additional ultrasound therapy (group III, p < 0.001), while mental subscores of SF-36 did not change significantly in any group. In conclusion, addition of therapeutic ultrasound to the traditional physical therapy showed a longitudinal positive effect on pain, functional status, and physical QoL in patients with hip osteoarthritis. The use of therapeutic ultrasound in the treatment of hip osteoarthritis should be encouraged, and it seems worthy to continue with large clinical trials on ultrasound in order to standardize the treatment modality in this patient group.     

Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study)

BACKGROUND: Only a minority of hypertensive individuals is adequately controlled for their hypertension, partially because reliable predictors for efficient antihypertensive drug therapy are lacking. METHODS: In a prospective, randomized, double-blind, cross-over, placebo-controlled study (The GENRES Study), 208 moderately hypertensive Finnish men (aged 35 to 60 years) were treated for 4 weeks with antihypertensive drugs from four different classes: amlodipine (5 mg), bisoprolol (5 mg), hydrochlorothiazide (25 mg), or losartan (50 mg) daily. Each individual received each of the four monotherapies in a randomized order. Four-week placebo periods were included before and between drug treatment periods. Antihypertensive responses were assessed with 24-h ambulatory and office measurements and analyzed according to age, body mass index, triceps skin fold thickness, waist-to-hip ratio, duration of hypertension, number of previous antihypertensive drugs, number of affected parents, and blood pressure (BP) levels, and profiles during placebo periods. RESULTS: The median BP responses in 24-h ambulatory recordings (systolic/diastolic) were 11/8 mm Hg for bisoprolol, 9/6 mm Hg for losartan, 7/5 mm Hg for amlodipine, and 5/2 mm Hg for hydrochlorothiazide. The highest pairwise within-subject correlations in BP responses were seen for the combinations of bisoprolol-losartan and amlodipine-hydrochlorothiazide. The BP responses to bisoprolol and losartan did not vary according to the variables. Amlodipine and hydrochlorothiazide responses were positively correlated with age, placebo BP level, and lower night-time dipping on placebo. CONCLUSIONS: Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies. The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness.     

Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo‐controlled randomized study

Aims

To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin.

Materials and Methods

In this double‐blind randomized study ( Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53‐91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m²) were randomized to ertugliflozin 5 mg once‐daily, 15 mg once‐daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52.

Results

A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3 mmol/mol]; eGFR, 87.9 mL/min/1.73 m²). After 26 weeks, placebo‐adjusted least squares (LS) mean changes in HbA1c from baseline were ?0.7% (?7.5 mmol/mol) and ?0.8% (?8.3 mmol/mol) for ertugliflozin 5 and 15 mg, respectively (both P < .001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg or ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7%‐14.1%) vs placebo (0%‐1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups.

Conclusions

Ertugliflozin added to metformin and sitagliptin was well‐tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions vs placebo over 52 weeks.     

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.     

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.     

Using motivational interviewing to promote adherence to antiretroviral medications: a randomized controlled study

The primary aim of this study was to test an intervention to support antiretroviral medication adherence among primarily low-income men and women with HIV. The study was a randomized controlled trial (Get Busy Living) with participants assigned to treatment (Motivational Interviewing [MI]) and control groups. Participants were recruited from an HIV/AIDS clinic in Atlanta, Georgia, US. Of those referred to the study, 247 completed a baseline assessment and were enrolled with 125 randomized to the intervention group and 122 to the control group. Participants were patients beginning antiretroviral therapy or changing to a new drug regimen. The intervention consisted of five MI sessions delivered by registered nurses in individual counselling sessions. Participants were paid for each session attended. The intervention sought to build confidence, reduce ambivalence and increase motivation for ART medication-taking. Medication adherence was measured by the Medication Event Monitoring System (MEMS) from the time of screening until the final follow-up conducted approximately 12 months following the baseline assessment. Participants in the intervention condition showed a trend towards having a higher mean percent of prescribed doses taken and a greater percent of doses taken on schedule when compared to the control group during the months following the intervention period. This effect was noted beginning at about the eighth month of the study period and was maintained until the final study month. Although the finding was weaker for overall percent of prescribed doses taken, the results for the percent of doses taken on schedule suggests that the MI intervention may be a useful approach for addressing specific aspects of medication adherence, such as adherrence to a specified dosing schedule.     

Efficacy and safety of acarbose add-on therapy in the treatment of overweight patients with Type 2 diabetes inadequately controlled with metformin: a double-blind, placebo-controlled study

This 6-month, double-blind, placebo-controlled, randomised, parallel-group study investigated the potential of acarbose add-on therapy for improving the glycaemic control of overweight patients with Type 2 diabetes and was inadequately controlled with metformin monotherapy. Patients were randomised to receive acarbose titrated up to 100 mg three times daily (n=74) or placebo (n=78). All patients were receiving metformin 850 mg twice or thrice daily before the study and continued to receive this dose throughout the study. The mean difference in glycated haemoglobin (HbA(1c)) (+/-S.D.) from baseline to endpoint was -0.7+/-1.2% U in the acarbose intention-to-treat (ITT) group, compared with +0.2+/-1.3% in the placebo ITT group (P=0.0001). Significantly, more patients in the acarbose group were classified as 'responders', with an HbA(1c) at the end of treatment of less than 7.0% or a decrease by at least 15% relative to baseline (acarbose vs. placebo; 42 vs. 17%; P=0.002). The difference in fasting blood glucose level from baseline to endpoint was -1.0+/-2.8 (S.D.) mmol/l in the acarbose ITT group, compared with +1.3+/-2.8 mmol/l in the placebo ITT group (P=0.0001), and for 2-h postprandial blood glucose level -1.4+/-3.8 vs. +1.1+/-3.5 mmol/l (P=0.0001). In all, 60% of patients in the acarbose group and 33% in the placebo group had an adverse event considered to be possibly or probably related to drug therapy, leading to withdrawal by 15 and 3%, respectively. The results indicate that acarbose has potential clinical utility for improving glycaemic control in overweight patients with Type 2 diabetes inadequately controlled with metformin.     

Phase III,randomized, double-blind,placebo-controlled study to evaluate the efficacy and safety of teneligliptin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise

Aims/IntroductionAlthough the efficacy of teneligliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.Materials and MethodsThis multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to <10.0% and fasting blood glucose <270 mg/dL. Patients were randomly assigned, in a 1:1 ratio, to treatment with 20 mg teneligliptin or a placebo (n = 127, each) administered orally once daily before breakfast for 24 weeks. Change in glycosylated hemoglobin from baseline to week 24 was the primary efficacy end‐point. Safety was assessed by the incidence of adverse events and adverse drug reactions.ResultsThe least square mean (LSM) change in glycosylated hemoglobin from baseline to week 24 was −0.95% with teneligliptin versus −0.14% with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −0.80% (P < 0.0001). For the secondary end‐point, from baseline to week 24, the LSM change in fasting blood glucose was −21.9 mg/dL with teneligliptin versus −1.4 mg/dL with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −20.5 mg/dL (P < 0.0001). The adverse event and adverse drug reaction incidence rates, including hypoglycemia, were similar in both groups.ConclusionsAt 24 weeks, teneligliptin was generally well tolerated and effective in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.     

The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.     

Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.