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.     

Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial

It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs ($3222 versus $4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.     

Twenty-four hour ambulatory blood pressure for the management of antihypertensive treatment: a randomized controlled trial

The aim of this study was to assess whether the use of 24-h blood pressure (BP) measurement in the management of antihypertensive therapy improves BP in patients with sustained hypertension. Patients with sustained hypertension (office BP > or =140/90 mm Hg, and 24-h systolic BP > or =130/80 mm Hg) were randomly assigned to a strategy using 24-h BP to manage antihypertensive treatment (target <130/80 mm Hg) or to a standard strategy using office BP (target <140/90 mm Hg). The primary end point was change in 24-h systolic BP at 1 year of follow-up. We included 136 patients in the primary analysis. After 1 year of follow-up, the change in 24-h systolic BP was significantly greater in the ambulatory BP group compared with the office BP group (mean difference (95% confidence interval) -3.6 (-7.0, -0.3), P=0.03). Intention-to-treat analysis revealed essentially unchanged results. The mean number of antihypertensive drugs per participant at 1 year of follow-up was 1.76+/-1.1 and 1.95+/-0.9 in the ambulatory and office BP group, respectively (P=0.049). The benefit of ambulatory BP monitoring was mainly seen in patients with previously known hypertension (mean difference -7.2 (-11.6, -2.8), P=0.002), but not in those with newly detected hypertension (mean difference 0.2 (-4.9, 5.4), P=0.93). In conclusion, using 24-h BP for the management of antihypertensive therapy in patients with sustained hypertension leads to a greater BP reduction compared with a standard treatment strategy using office BP, although fewer antihypertensive drugs were used in the ambulatory BP group.     

A randomized controlled trial of the effects of three antihypertensive agents on blood pressure control and quality of life in older women

We conducted a multicenter, randomized, double-blind, parallel group trial to compare the impact of titrated doses of atenolol (50 to 100 mg once a day), enalapril (5 to 20 mg once a day), and diltiazem (sustained release) (60 to 180 mg twice a day) on blood pressure and quality of life in older hypertensive women. Two hundred forty-two patients were randomized. Dose titration was completed by week 4 after randomization, and the maintenance phase was completed at week 16. Diltiazem (sustained release) demonstrated greater diastolic blood pressure lowering at both weeks 8 and 16 by an intent-to-treat analysis. At week 16, diltiazem changed diastolic blood pressure -13.7 +/- 0.7 mm Hg compared with -10.8 +/- 1.1 mm Hg for atenolol, and -10.5 +/- 0.9 mm Hg for enalapril. Diltiazem also demonstrated greater lowering of systolic blood pressure at week 3, but these differences in systolic blood pressure had decreased by week 16. More patients were classified as treatment failures during the 16 weeks of the trial for atenolol (15%) than for diltiazem (2.5%), while the treatment failure rate was intermediate with enalapril (8%). Total rates of adverse events were equivalent across the three treatment arms. There were few significant differences in the impact of the three treatments on mean scores of quality-of-life measures at week 16. There was a trend for atenolol to have somewhat worse quality-of-life scores, but none of these differences were statistically significant. In conclusion, all three treatment regimens were effective in lowering diastolic blood pressure without significant differences in rates of adverse events or deleterious effects on quality of life.     

Healing pressure ulcers with collagen or hydrocolloid: a randomized,controlled trial

OBJECTIVES: To compare the effects of topical collagen and hydrocolloid on pressure ulcer healing. DESIGN: Randomized (allocation concealed), single-blind (outcome assessors), controlled trial with 8-week follow-up. SETTING: Eleven nursing homes in central Illinois. PARTICIPANTS: Sixty-five patient-residents with Stage II or III pressure ulcers: median age 83.1, median Braden score 12, 63% female, 80% Stage II ulcers, and 20% Stage III ulcers. Exclusion criteria included cellulitis and osteomyelitis. INTERVENTION: Thirty-five patients were allocated to topical collagen daily, 30 to topical hydrocolloid twice weekly. MEASUREMENTS: The primary outcome was complete healing within 8 weeks. Secondary outcomes were time to heal, ulcer area healed per day, linear healing of wound edge, and cost of therapy. RESULTS: Analysis by intention to treat revealed similar complete ulcer healing within 8 weeks in collagen (51%) and hydrocolloid (50%) recipients (difference 1%, 95% confidence interval (CI) = 26-29%). Mean healing time was similar: collagen healed in 5 weeks (95% CI = 4-6), hydrocolloid healed in 6 weeks (95% CI = 5-7). Mean area healed per day was 6 mm(2)/d in both treatment groups. Mean linear healing of the wound edge was 3 mm in both groups. In multivariate analysis, baseline ulcer depth was the only independent predictor of complete ulcer healing within 8 weeks (odds ratio = 0.56, 95% CI = 0.38-0.81). Cost analysis favored hydrocolloid. CONCLUSIONS: There were no significant differences in healing outcome between collagen and hydrocolloid. Collagen was more expensive and offered no major benefits to patients otherwise eligible for hydrocolloid treatment.     

Initial antihypertensive drug therapy. Final report of a randomized, controlled trial comparing alpha-blocker and diuretic

We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of amlodipine and other classes of antihypertensive drugs on long-term blood pressure variability: Evidence from randomized controlled trials

Blood pressure (BP) is monitored and managed to prevent cardiovascular complications of hypertension, but BP variability (BPV) has not been sufficiently studied. This analysis assessed whether patients receiving amlodipine vs other antihypertensive agents had lower BPV after ≥12 weeks of treatment. Studies were included if individual subject data were available, had ≥1 active comparator, and treatment duration was ≥12 weeks. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) of systolic BP across visits from 12 weeks. Individual trial and meta-analyses were performed for SD- and CV-based methodology. Five studies (47,558 BPV-evaluable patients) were included. Patient characteristics were largely consistent across the studies, but BP measurements varied from ∼4 months to ∼6 years. BPV with amlodipine was significantly (P < .0001) lower vs atenolol and lisinopril; significantly (P < .0001) lower than enalapril in one study and numerically, but not significantly lower in another; and similar to chlorthalidone and losartan. Meta-analysis revealed a treatment difference (standard error) for amlodipine vs all active comparators of −1.23 (0.46; P = .008) mm Hg using SD and −0.86 (0.31; P = .005) using CV. These findings suggest that amlodipine is effective for minimizing BPV. Future studies need to confirm a causal link between BPV and cerebrovascular/cardiovascular outcomes.     

Comparison of antihypertensive and metabolic effects of losartan and losartan in combination with hydrochlorothiazide--a randomized controlled trial

INTRODUCTION: Losartan is an angiotensin II receptor blocker indicated for treatment of hypertension. It also inhibits platelet agreggation through blockade of thromboxane A2/ prostaglandin H2 receptors, and has a uricosuric effect We determined the effect on ambulatory blood pressure (ABP) of 100 mg losartan monotherapy (L100) versus 50 mg losartan/12.5 mg hydrochlorothiazide (HCTZ) combination therapy (L50H12.5C), in patients uncontrolled on 50 mg losartan. We also assessed the effects of losartan on platelet aggregation and serum urate at these clinically relevant doses. METHODS: This was a randomized, double-blind trial of L100 versus L50H12.5C, in moderate hypertensives (sitting diastolic blood pressure (DBP) >or = 95 mmHg and < 120 mmHg). After 4 weeks of placebo run-in, patients received 50 mg losartan for 6 weeks; patients uncontrolled (sitting DBP > or = 95 mmHg) were randomized to L100 or L50H12.5C for a further 6 weeks. Platelet function was assessed by measuring percentage inhibition of platelet aggregation, and serum uric acid was also measured. RESULTS: Monotherapy with 50 mg losartan reduced ABP by 16.0/9.9 mmHg during the day and 9.8/5.5 mmHg at night However, 16 out of 24 (66%) patients had uncontrolled blood pressure on this treatment L50H12.5C further reduced daytime ABP by 10.7(10.7)/8.4(6.5) mmHg mean (SEM) compared with L100 (-5.3(9.7)/-2.3(4.8), P = 0.013). 50 mg losartan and L100 did not affect platelet function or uric acid levels beyond placebo values; treatment with L50H12.5C was associated with a significant rise in serum urate above levels obtained on 50 mg losartan (366.9(67.6) versus 331.6(65.0), P=0.006), to levels similar to placebo (358.8(80.9)). CONCLUSION: L50H12.5C is an effective antihypertensive regimen in patients with moderate hypertension that is uncontrolled on 50 mg losartan monotherapy, and is the preferred treatment option in these patients compared with increasing the dose of losartan. The additional benefit of losartan on platelet inhibition was not evident in our population at these doses; however, there was evidence to suggest that the uricosuric effects of losartan might ameliorate the uric acid retention effects of therapy with hydrochlorothiazide.     

Quality of life on antihypertensive therapy: a randomized double-blind controlled trial of captopril and atenolol

A randomized double-blind study lasting 2 months was performed with either 25 mg captopril twice a day or 50 mg atenolol once a day in 125 patients with established diastolic hypertension (diastolic blood pressure greater than 95 mmHg) identified during a population screening programme of subjects aged less than 65 years. Quality of life was assessed from self-completed questionnaires. A significant fall in diastolic blood pressure occurred with both captopril (106.7 +/- 7.0 to 98.6 +/- 8.6 mmHg) and atenolol (107.4 +/- 7.5 to 98.2 +/- 8.1 mmHg) but there was no difference between the two drugs in the size of the fall. A measure of the number of symptomatic complaints, the symptom complaint rate, decreased with both drugs, by 1.3% for captopril and 3.1% for atenolol, but the difference between the drugs was not significant [1.8%; 95% confidence interval (Cl) - 1.3%, 4.9%]. There was a significant increase in the reporting of cough and runny nose in those on captopril compared with atenolol. A health index increased by 1.1% with captopril in comparison with no change on atenolol (difference 1.1%; 95% Cl - 2.0%, 4.2%). Psychological well-being was measured using the Symptom Rating Test. The improvement in total score was 1.4% with captopril and 2.3% with atenolol. The difference of 0.9% was not statistically significant (95% Cl - 1.2%, 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Octreotide enhances portal pressure reduction induced by propranolol in cirrhosis: a randomized, controlled trial

BACKGROUND: In vitro, octreotide potentiates vasoconstriction in isolated, preconstricted, mesenteric arterial vessels. In cirrhotic patients, portal pressure (HVPG) reduction induced by propranolol is partly due to splanchnic vasoconstriction. AIM: To evaluate HVPG effects of octreotide administration in cirrhotic patients receiving long-term propranolol. PATIENTS AND METHODS: A randomized, controlled trial. First study: a total of 28 patients were studied at baseline and 30 and 60 minutes after octreotide (200 mug) (N = 14) or placebo (N = 14) and then treated with propranolol for approximately 30 days (106 +/- 5 mg/day). Second study: after baseline evaluation patients received octreotide or placebo as they were assigned to in the first study and measurements repeated 30 and 60 minutes later. RESULTS: In the first study baseline HVPG was 18.7 +/- 0.9 mmHg and decreased to 17.1 +/- 1.1 mmHg and 17.1 +/- 1.0 mmHg (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Eight patients decreased their HVPG after octreotide. In the second study baseline HVPG was 15.6 +/- 1.3 mmHg (P < 0.01 vs baseline HVPG in first study) and decreased to 14.1 +/- 1.2 mmHg and 14.1 +/- 1.3 mmHg (25.7 +/- 5% lower than baseline HVPG in the first study, P < 0.01) (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Nine patients (2 responders/7 nonresponders to propranolol) decreased their HVPG after octreotide. Octreotide effects may be mediated by potentiation and additive mechanisms. CONCLUSIONS: Octreotide enhances HVPG reduction induced by propranolol in cirrhotic patients.     

Additional antihypertensive effect of drugs in hypertensive subjects uncontrolled on diltiazem monotherapy: a randomized controlled trial using office and home blood pressure monitoring

The purpose of this study was to compare several diltiazem-based antihypertensive drug combinations and assess the usefulness of home blood pressure monitoring in the evaluation of the efficacy of combination pharmacotherapy. Sixteen general practitioners recruited hypertensive subjects uncontrolled on diltiazem monotherapy, who were randomized to receive eight weeks of add-on therapy with a diuretic (chlorthalidone), a dihydropyridine calcium antagonist (felodipine), an ACE inhibitor (lisinopril), or an angiotensin blocker (valsartan). Sitting office and home blood pressure was measured using electronic devices A&D 767. A total of 211 patients were randomized, and 185 completed the study. Of 52 subjects randomized to felodipine, 15 were withdrawn due to ankle edema. The additional antihypertensive effect of the second drug was smaller in 18 subjects with a white coat effect (p < 0.01). All combinations produced a significant decline in office (21.2 +/- 14.8 / 7.7 +/- 9.7 mmHg) and home (17.1 +/- 11.9 / 6.0 +/- 7.0) blood pressure (systolic / diastolic, p < 0.001). There were no differences in the efficacy of the four combinations assessed using office or home blood pressure monitoring. These data suggest that diuretics, dihydropyridines, ACE inhibitors, and angiotensin receptor blockers provide significant additional antihypertensive effects in hypertensive patients uncontrolled on diltiazem monotherapy. The diltiazem-dihydropyridine combination is often intolerable because of ankle edema. Home blood pressure monitoring is useful in the assessment of the efficacy of combination pharmacotherapy and also allows for the detection of subjects who do not require treatment intensification.     

Comparison of alprazolam versus captopril in high blood pressure: a randomized controlled trial

OBJECTIVE. Anxiety is an important cause of acute blood pressure (BP) elevation. However, the role of anxiolysis in this situation is still controversial. In this study, the relationship of anxiety with BP and the effect of anxiolytic treatment on BP were investigated. METHODS. Emergency department (ED) patients with an initial systolic BP (SBP) ≥ 160 mmHg or diastolic BP (DBP) ≥ 100 mmHg but no end organ damage were approached for inclusion in the study. In those consenting to participate, anxiety levels were measured using the State-Trait Anxiety Index (STAI) and Visual Analog Scale for Anxiety (VAS-A). Patients were randomly assigned to receive oral alprazolam 0.5 mg or captopril 25 mg. BP and anxiety levels were measured at baseline and at 1 and 2 h after administration of the study medication. RESULTS. Of 133 patients meeting inclusion criteria, 53 patients agreed to participate. Of these, 27 patients (50.9%) received captopril and 26 patients (49.1%) received alprazolam. The majority of the patients had a high-level trait (96.2%, n = 51) and state anxiety (81.1%, n = 43). The mean SBP and VAS-A values of both patient groups dropped significantly over the 2 h, with no significant difference between the two groups. A significant association between SBP and VAS-A scores was found (F((2,50)) = 6.27, p = 0.004). CONCLUSION: A significant association exists between the level of BP and anxiety in hypertensive ED patients. Alprazolam is as effective as captopril in lowering BP in ED patients with an initial SBP > 160 mmHg.