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1.
Br J Clin Pharmacol ; 85(12): 2707-2713, 2019 12.
Article in English | MEDLINE | ID: mdl-31471972

ABSTRACT

Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.


Subject(s)
Antihypertensive Agents/therapeutic use , Drug Prescriptions/statistics & numerical data , Drug Utilization/trends , Hypertension/drug therapy , Sodium Chloride Symporter Inhibitors/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Bendroflumethiazide/administration & dosage , Bendroflumethiazide/adverse effects , Bendroflumethiazide/therapeutic use , Blood Pressure/drug effects , Humans , Indapamide/administration & dosage , Indapamide/adverse effects , Indapamide/therapeutic use , Practice Guidelines as Topic , Sodium Chloride Symporter Inhibitors/administration & dosage , Sodium Chloride Symporter Inhibitors/adverse effects
2.
Cochrane Database Syst Rev ; 8: CD008276, 2017 08 16.
Article in English | MEDLINE | ID: mdl-28813123

ABSTRACT

BACKGROUND: Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age. OBJECTIVES: To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both. DATA COLLECTION AND ANALYSIS: The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity. MAIN RESULTS: The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average. AUTHORS' CONCLUSIONS: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Adult , Antihypertensive Agents/adverse effects , Bendroflumethiazide/therapeutic use , Blood Pressure/drug effects , Cause of Death , Coronary Disease/mortality , Coronary Disease/prevention & control , Humans , Hypertension/mortality , Methyldopa/therapeutic use , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Patient Dropouts/statistics & numerical data , Propranolol/therapeutic use , Randomized Controlled Trials as Topic , Stroke/mortality , Stroke/prevention & control , Young Adult
3.
BMJ Case Rep ; 20162016 Feb 16.
Article in English | MEDLINE | ID: mdl-26884077

ABSTRACT

We report the association between excessive consumption of green tea and hypokalaemia in an Oriental couple. Both patients were asymptomatic and the abnormal electrolyte level was only detected on routine blood tests. When they were advised to reduce the consumption of green tea, the abnormally low potassium level was reversed. We have not found such an association reported in the medical literature. The health benefits of green tea consumption are well publicised but the potential side-effects of overconsumption are less well known. We would like to report this association to alert clinicians about this potentially serious complication. This is especially relevant for those who are also taking prescribed medications that can lower potassium levels and/or sensitise patients to potential harm from hypokalaemia.


Subject(s)
Drinking Behavior , Hypokalemia/etiology , Tea/adverse effects , Aged , Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Bendroflumethiazide/therapeutic use , Female , Humans , Hypertension/complications , Hypertension/drug therapy , Lisinopril/therapeutic use , Male
4.
BMJ Case Rep ; 20162016 Jan 18.
Article in English | MEDLINE | ID: mdl-26783007

ABSTRACT

Percutaneous drainage proved to be successful in managing a renal subcapsular haematoma that was causing acute renal failure and hypertension in a 74-year-old woman. The patient presented with oliguria, nausea and malaise 2 days after a ureteronephroscopic procedure with biopsies of a suspected urothelial neoplasm in the right renal pelvis. The left kidney had recently been removed due to renal cell carcinoma. At admission, the patient's blood pressure and plasma creatinine levels were massively elevated. Ultrasonography revealed a moderate right-sided renal subcapsular haematoma. When the patient did not respond to antihypertensive treatment, Page kidney was suspected. A pigtail catheter was placed in the haematoma and, shortly after drainage, the diuresis resumed and plasma creatinine together with blood pressure decreased. This condition had previously been managed by open surgery, but recent case reports have described successful management by laparoscopy-assisted and radiology-assisted drainage, as described in this case report.


Subject(s)
Acute Kidney Injury/etiology , Antihypertensive Agents/therapeutic use , Bendroflumethiazide/therapeutic use , Drainage/methods , Hematoma/complications , Hypertension/etiology , Metoprolol/therapeutic use , Acute Kidney Injury/therapy , Aged , Blood Pressure/physiology , Female , Hematoma/therapy , Humans , Kidney/pathology
9.
Hypertension ; 59(6): 1104-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22547443

ABSTRACT

Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥ 2 different monotherapy dose arms, follow-up duration ≥ 4 weeks, and baseline washout of medication ≥ 2 weeks, were identified using Embase (1980-2010 week 50), Medline (1950-2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency series: bendroflumethiazide>chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges.


Subject(s)
Bendroflumethiazide/therapeutic use , Blood Pressure/drug effects , Chlorthalidone/therapeutic use , Hydrochlorothiazide/therapeutic use , Potassium/blood , Uric Acid/blood , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Bendroflumethiazide/administration & dosage , Chlorthalidone/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Hydrochlorothiazide/administration & dosage , Hypertension/blood , Hypertension/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome
10.
J Hypertens ; 29(10): 2004-13, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21881528

ABSTRACT

BACKGROUND: Resistant hypertension is a well recognized clinical entity, which has been inadequately researched to date. METHODS: A multivariable Cox model was developed to identify baseline predictors of developing resistant hypertension among 3666 previously untreated Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) patients and construct a risk score to identify those at high risk. Secondary analyses included evaluations among all 19 257 randomized patients. RESULTS: One-third (1258) of previously untreated, and one-half (9333) of all randomized patients (incidence rates 75.2 and 129.7 per 1000 person-years, respectively) developed resistant hypertension during a median follow-up of 5.3 and 4.8 years, respectively. Increasing strata of baseline SBP (151-160, 161-170, 171-180, and >180 mmHg) were associated with increased risk of developing resistant hypertension [hazard ratio 1.24 (95% confidence interval, CI 0.81-1.88), 1.50 (1.03-2.20), 2.15 (1.47-3.16), and 4.43 (3.04-6.45), respectively]. Diabetes, left ventricular hypertrophy, male sex, and raised BMI, fasting glucose, and alcohol intake were other significant determinants of resistant hypertension. Randomization to amlodipine ±â€Šperindopril vs. atenolol ±â€Šthiazide [0.57 (0.50-0.60)], previous use of aspirin [0.78 (0.62-0.98)], and randomization to atorvastatin vs. placebo [0.87 (0.76-1.00)] significantly reduced the risk of resistant hypertension. Secondary analysis results were similar. The risk score developed allows accurate risk allocation (Harrell's C-statistic 0.71), with excellent calibration (Hosmer-Lemeshow χ statistics, P = 0.99). A 12-fold (8.4-17.4) increased risk among those in the highest vs. lowest risk deciles was apparent. CONCLUSION: Baseline SBP and choice of subsequent antihypertensive therapy were the two most important determinants of resistant hypertension in the ASCOT population. Individuals at high risk of developing resistant hypertension can be easily identified using an integer-based risk score.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Aged , Algorithms , Amlodipine/therapeutic use , Atenolol/therapeutic use , Bendroflumethiazide/therapeutic use , Diuretics/therapeutic use , Drug Resistance , Female , Humans , Hypertension/physiopathology , Ireland , Male , Middle Aged , Perindopril/therapeutic use , Risk Factors , Scandinavian and Nordic Countries , United Kingdom
11.
J Hypertens ; 28(1): 170-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20009770

ABSTRACT

OBJECTIVES: We hypothesized that the aldosterone: renin ratio (ARR) predicts the antihypertensive response to mineralocorticoid receptor antagonist, spironolactone (SPIRO), when compared with bendroflumethiazide (BFZ). METHODS: We conducted a randomized, crossover, trial on hypertensive patients with either high ARR (HARR defined as >750 and plasma aldosterone >250 pmol/l) or low ARR (LARR defined as <300 and plasma renin activity <10 ng/ml per h). Each group took SPIRO 50 mg once daily for 12 weeks and BFZ 2.5 mg once daily for 12 weeks in random order separated by 2-week washout. Patients with mean 24-h systolic ambulatory blood pressure (SABP) at least 140 mmHg were included. Primary endpoint was difference in SABP between SPIRO and BFZ in patients with HARR compared with those with LARR. RESULTS: One hundred and eleven patients (60 HARR and 51 LARR) completed the study. SABP at 12 weeks in the HARR group was 129.4 mmHg on SPIRO and 134.4 mmHg on BFZ [difference -5.01; 95% confidence interval (CI) -7.51, -2.52; P < 0.0002]. In the LARR group, SABP was 129.7 mmHg on SPIRO and 133.1 mmHg on BFZ [difference -3.43 (95% CI -6.18, -0.68) P < 0.01]. Difference between groups (HARR vs. LARR) was -1.58 mmHg (95% CI 5.25, -2.08; not significant, P = 0.394). In a secondary analysis of the overall study population of 111 patients, SABP reduction with SPIRO 50 mg was superior to BFZ 2.5 mg [SPIRO -14.8 mmHg, BFZ -10.5 mmHg, difference -4.29 mmHg (95% CI -6.12, -2.46)]. Results were similar for secondary endpoints. Plasma renin activity or aldosterone did not predict blood pressure response to SPIRO. Results were independent of concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. CONCLUSION: The ARR did not predict the blood pressure response to SPIRO. SPIRO 50 mg was significantly more effective than BFZ 2.5 mg in lowering SABP irrespective of baseline ARR, plasma renin activity or aldosterone.


Subject(s)
Aldosterone/blood , Bendroflumethiazide/therapeutic use , Diuretics/therapeutic use , Hypertension/drug therapy , Renin/blood , Spironolactone/therapeutic use , Blood Pressure/drug effects , Blood Pressure/physiology , Cross-Over Studies , Drug Therapy, Combination , Female , Humans , Hyperaldosteronism/drug therapy , Hyperaldosteronism/physiopathology , Hypertension/blood , Hypertension/physiopathology , Male , Middle Aged , Predictive Value of Tests , Treatment Outcome
12.
J Am Coll Cardiol ; 54(13): 1154-61, 2009 Sep 22.
Article in English | MEDLINE | ID: mdl-19761936

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the effect of baseline heart rate on the efficacy of atenolol-based compared with amlodipine-based therapy in patients with hypertension uncomplicated by coronary heart disease in the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm). BACKGROUND: Heart rate is an established risk factor for cardiovascular events. Consequently, it is a widely held belief that beta-blockers should be prescribed for management of hypertension in patients with higher heart rates. METHODS: Patients with atrial fibrillation or taking rate-limiting antihypertensive drugs at baseline were excluded. Primary analyses used Cox models to investigate the potential attenuation of the treatment effect with higher baseline heart rate on total cardiovascular events and procedures (TCVP) via introduction of an interaction term. Secondary analyses assessed coronary and total stroke outcomes. RESULTS: Primary unadjusted analyses included 12,759 patients and 1,966 TCVP. At the final visit, mean heart rate reduction from baseline was 12.0 (SD 13.7) and 1.3 (SD 12.1) beats/min in atenolol- and amlodipine-based groups, respectively. There was a reduction in TCVP in those allocated amlodipine-based therapy compared with atenolol-based therapy (unadjusted hazard ratio: 0.81, p < 0.001). This benefit was unattenuated at higher heart rates (interaction p value = 0.81). Similar results were obtained for coronary and total stroke outcomes. CONCLUSIONS: There was no evidence that the superiority of amlodipine-based over atenolol-based therapy for patients with hypertension uncomplicated by coronary heart disease was attenuated with higher baseline heart rate. These data suggest that, in similar hypertensive populations without previous or current coronary artery disease, higher baseline heart rate is not an indication for preferential use of beta-blocker-based therapy.


Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Atenolol/therapeutic use , Heart Rate , Hypertension/drug therapy , Hypertension/physiopathology , Aged , Bendroflumethiazide/therapeutic use , Coronary Disease/epidemiology , Coronary Disease/physiopathology , Coronary Disease/prevention & control , Europe , Female , Humans , Male , Middle Aged , Perindopril/therapeutic use , Proportional Hazards Models , Treatment Outcome
13.
Am J Hypertens ; 22(11): 1227-31, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19763121

ABSTRACT

BACKGROUND: Diastolic dysfunction is common in early hypertension. We hypothesized that improvement in diastolic dysfunction is blood pressure (BP) dependent and may occur early with treatment in newly diagnosed untreated hypertensive patients. METHODS: Forty untreated hypertensive subjects (age 52 +/- 1.4 years, mean +/- s.e.m.) with diastolic dysfunction based on Canadian Consensus Guidelines, received either bendroflumethiazide 2.5 mg (1.25 mg for the first month), or candesartan 16 mg (8 mg for the first month). Left ventricular (LV) structure and function, early diastolic velocity (E') and systolic velocity, and systolic myocardial velocity (Sm) were assessed echocardiographically using M-mode, 2-dimensional, and tissue Doppler imaging (TDI) before and at 1 and 3 months following treatment. RESULTS: Antihypertensive treatment reduced BP significantly at 3 months (168 +/- 2/97 +/- 1-143 +/- 2/86 +/- 1 mm Hg, P < 0.0001). Both drugs had similar and significant effects on TDI E' which increased from 7.8 +/- 0.2 to 10 +/- 0.3 cm/s (P < 0.001). The improvement in TDI E' was independent of LV mass index (LVMI) regression but was significantly related to the improvement in Sm (r = 0.73, P < 0.0001) and the fall in systolic BP (R = 0.51, P < 0.001). Normalization of diastolic function was associated with better control of BP (130 +/- 4/81 +/- 2 mm Hg vs. 149 +/- 2/88 +/- 1 mm Hg, P < 0.05). In a stepwise regression model, reduction in systolic BP (P < 0.001) and TDI Sm (P < 0.0001) emerged as independent determinants of improvement in TDI E' with no contribution from age, gender or change in relative wall thickness (RWT) (R(2) = 0.68, P < 0.0001). CONCLUSIONS: Achieving good BP control and enhancement in systolic function determines the improvement in diastolic function in early hypertension.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Ventricular Dysfunction, Left/drug therapy , Bendroflumethiazide/therapeutic use , Benzimidazoles/therapeutic use , Biphenyl Compounds , Blood Pressure/drug effects , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Hemodynamics/drug effects , Humans , Hypertension/complications , Hypertension/physiopathology , Male , Middle Aged , Regression Analysis , Tetrazoles/therapeutic use , Ultrasonography , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
14.
Ugeskr Laeger ; 170(36): 2782-4, 2008 Sep 01.
Article in Danish | MEDLINE | ID: mdl-18761872

ABSTRACT

ASCOT compared the effect of atenolol combined with a thiazide versus amlodipine with perindopril in hypertensive patients. It also studied the effect of atorvastatin in those with normal cholesterol. ASCOT concluded that reductions in cardiovascular events with atorvastatin were significant, and that amlodipine-based treatment prevented more cardiovascular events. The latter seemed to be due to better control of central blood pressure. Both statin and amlodipine-based treatments were cost-effective. According to the ASCOT study, it does matter how blood pressure is lowered.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Amlodipine/therapeutic use , Anticholesteremic Agents/therapeutic use , Antihypertensive Agents/economics , Atenolol/therapeutic use , Atorvastatin , Bendroflumethiazide/therapeutic use , Cardiovascular Diseases/prevention & control , Cost-Benefit Analysis , Diuretics/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Evidence-Based Medicine , Heptanoic Acids/therapeutic use , Humans , Hypertension/complications , Perindopril/therapeutic use , Pyrroles/therapeutic use , Treatment Outcome
16.
Int J Clin Pharmacol Ther ; 46(2): 72-83, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18218287

ABSTRACT

OBJECTIVE: Older people experience more concurrent illnesses, are prescribed more medications and suffer more adverse drug events than younger people. Many drugs predispose older people to adverse events such as falls and cognitive impairment, thus increasing morbidity and health resource utilization. At the same time, older people are often denied potentially beneficial, clinically indicated medications without a valid reason. We aimed to validate a new screening tool of older persons' prescriptions incorporating criteria for potentially inappropriate drugs called STOPP (Screening Tool of Older Persons' Prescriptions) and criteria for potentially appropriate, indicated drugs called START (Screening Tool to Alert doctors to Right, i.e. appropriate, indicated Treatment). METHODS: A Delphi consensus technique was used to establish the content validity of STOPP/START. An 18-member expert panel from academic centers in Ireland and the United Kingdom completed two rounds of the Delphi process by mail survey. Inter-rater reliability was assessed by determining the kappa-statistic for measure of agreement on 100 data-sets. RESULTS: STOPP is comprised of 65 clinically significant criteria for potentially inappropriate prescribing in older people. Each criterion is accompanied by a concise explanation as to why the prescribing practice is potentially inappropriate. START consists of 22 evidence-based prescribing indicators for commonly encountered diseases in older people. Inter-rater reliability is favorable with a kappa-coefficient of 0.75 for STOPP and 0.68 for START. CONCLUSION: STOPP/START is a valid, reliable and comprehensive screening tool that enables the prescribing physician to appraise an older patient's prescription drugs in the context of his/her concurrent diagnoses.


Subject(s)
Drug Prescriptions/statistics & numerical data , Drug Utilization Review/methods , Health Services for the Aged/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Abbreviations as Topic , Age Factors , Aged , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Bendroflumethiazide/therapeutic use , Clopidogrel , Delphi Technique , Digoxin/therapeutic use , Digoxin/toxicity , Diuretics/therapeutic use , Drug Prescriptions/classification , Drug Therapy/standards , Drug Therapy/statistics & numerical data , Drug Utilization Review/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions , Glomerular Filtration Rate/drug effects , Health Services for the Aged/organization & administration , Humans , Ireland , Metformin/therapeutic use , Reproducibility of Results , Risk Factors , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Time Factors , United Kingdom
18.
Circulation ; 116(3): 268-75, 2007 Jul 17.
Article in English | MEDLINE | ID: mdl-17606839

ABSTRACT

BACKGROUND: There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's. Our primary hypothesis was that in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. METHODS AND RESULTS: Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K+, elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of > or = 20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg (P<0.005). Amiloride 40 mg was as effective as the other diuretics. Biochemical indices of natriuresis showed bendroflumethiazide to be less effective than either spironolactone or amiloride; plasma renin rose 4-fold on spironolactone but only 2-fold on bendroflumethiazide (P=0.003). CONCLUSIONS: In hypertensive patients with a low plasma renin but normal K+, bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone. Because this result differs from that expected in primary hyperaldosteronism, our finding argues against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism. However, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na+ retention of low-renin hypertension.


Subject(s)
Aldosterone/blood , Amiloride/therapeutic use , Hypertension/drug therapy , Losartan/therapeutic use , Renin/blood , Sodium Chloride Symporter Inhibitors/therapeutic use , Spironolactone/therapeutic use , Aged , Bendroflumethiazide/therapeutic use , Cross-Over Studies , Double-Blind Method , Female , Humans , Hypertension/blood , Male , Middle Aged , Single-Blind Method
19.
Am J Hypertens ; 20(6): 699-704, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17531931

ABSTRACT

BACKGROUND: Different antihypertensive therapies may exert benefits via not only a reduction in blood pressure but also in improving the risk of thrombosis. METHODS: We tested the hypothesis that a more modern antihypertensive drug regimen (ie, amlodipine +/- perindopril) would have a more beneficial effect on hemorheological markers (white blood-cell count [WCC], plasma viscosity [PV], hematocrit [HCT], and fibrinogen)--and on plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation), compared with an older antihypertensive drug regimen (ie, atenolol +/- bendroflumethiazide). RESULTS: After 6 months, PV, sP-sel, and HCT fell in both groups (P < .01), while fibrinogen was unchanged. However, those 74 patients randomized to amlodipine +/- perindopril had significant reductions in WCC (P = .005), with no significant changes in vWF or platelet count. Conversely, in those 85 patients randomized to atenolol +/- bendroflumethiazide, there were significant reductions in vWF (P = .001) and platelet count (P = .011) but no significant reductions in WCC. There were no significant differences in the levels of any of the variables between the two arms of the trial, nor a significant difference in the magnitude of reduction between the two treatment arms. CONCLUSIONS: Within the constraints of this substudy design, there was no differential effect apparent of the two antihypertensive treatment arms on hemorheological parameters or endothelial and platelet function (as assessed by vWF and sP-sel), suggesting that other pathophysiological mechanisms may be involved.


Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , P-Selectin/blood , Vascular Resistance/drug effects , von Willebrand Factor/metabolism , Adrenergic beta-Antagonists/pharmacology , Adrenergic beta-Antagonists/therapeutic use , Aged , Amlodipine/pharmacology , Amlodipine/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Atenolol/pharmacology , Atenolol/therapeutic use , Bendroflumethiazide/pharmacology , Bendroflumethiazide/therapeutic use , Blood Flow Velocity/drug effects , Blood Pressure/physiology , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Diuretics/pharmacology , Diuretics/therapeutic use , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Female , Humans , Male , Middle Aged , P-Selectin/drug effects , Perindopril/pharmacology , Perindopril/therapeutic use , Platelet Activation/drug effects , Platelet Activation/physiology , United Kingdom , von Willebrand Factor/drug effects
20.
BMC Cardiovasc Disord ; 7: 14, 2007 May 09.
Article in English | MEDLINE | ID: mdl-17490489

ABSTRACT

BACKGROUND: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. METHODS/DESIGN: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective--To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives--To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide. DISCUSSION: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.


Subject(s)
Aldosterone/blood , Bendroflumethiazide/therapeutic use , Hypertension/drug therapy , Renin/blood , Spironolactone/therapeutic use , Bendroflumethiazide/pharmacology , Cross-Over Studies , Double-Blind Method , Humans , Hypertension/blood , Spironolactone/pharmacology
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