Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study The stroke preventive effect in elderly hypertensives cannot fully be explained by the reduction in office blood pressure--insights from the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Effectiveness of Add-On Low-Dose Diuretics in Combination Therapy for Hypertension: Losartan/Hydrochlorothiazide vs. Candesartan/Amlodipine Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. Potassium supplementation in the treatment of idiopathic postural hypotension. Potassium chloride lowers blood pressure and causes natriuresis in older patients with hypertension. Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Effect of allopurinol on blood pressure and aortic compliance in hypertensive patients Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade Use of diuretics is associated with reduced risk of Alzheimer's disease: the Cache County Study
Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs OBJECTIVE To study whether the cardiovascular preventive effect of antihypertensive therapy can be explained solely by the reduction in office blood pressure , and to what extent the risk of stroke and cardiac events is associated with in- study diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) . DESIGN The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omized , double-blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70 - 84 years . The study group comprised 1,627 elderly patients ( mean blood pressure 195/102 mm Hg ; mean age 75.7 , SD 3.7 ; 63 % females ) . The average follow-up was 25 months ( range 6 - 65 months ) . No patient was lost to follow-up . METHOD We applied a Poisson model taking current age , sex , treatment , DBP and SBP into account for all patients in the study . The constants of the model were estimated by the maximum likelihood method . RESULTS The risk of stroke was significantly lower ( 42 % , p = 0.0402 ) for a patient on active therapy than for a patient on placebo having the same blood pressure level , age , and sex . There was a corresponding , non-significant , reduction in cardiac events of 21 % . In the whole study group the risk of stroke increased by 3 % per mmHg ( p = 0.0247 ) with increasing diastolic blood pressure for a given systolic pressure . The corresponding value for cardiac events was 2 % per mmHg ( p = 0.0376 ) . CONCLUSION In STOP-Hypertension we found a substantial risk reduction in stroke in actively treated patients , which was not solely explained by the blood pressure reduction obtained by treatment with beta-blockers and a potassium-sparing diuretic combination In guidelines , a combination therapy of two or more antihypertensives is recommended for treatment of hypertension where monotherapy is ineffective . Although diuretics or calcium channel blockers are commonly used as add-ons to angiotensin receptor blocker ( ARB ) , the most effective and safe combination has not been established . In this r and omized 4-month study , the efficacy and safety were compared between an ARB/diuretics ( losartan/hydrochlorothiazide [ HCTZ ] ) combination and the most prescribed combination , ARB/calcium channel blocker ( c and esartan/amlodipine ) in hypertensive patients for whom 8 mg/day of c and esartan proved ineffective . After 36 patients were recruited and allocated into two groups , changes in blood pressure ( BP ) and laboratory values were analyzed in 31 patients : 16 patients received losartan ( 50 mg/day)/HCTZ ( 12.5 mg/day ) ( L/H group ) , and 15 patients received c and esartan ( 8 mg/day)/amlodipine ( 5 mg/day ) ( C/A group ) after 5 patients were withdrawn . After 4 months , L/H significantly ( p<0.001 ) reduced mean systolic BP (SBP)/diastolic BP ( DBP ) from baseline 160/89±13/11 mmHg to 140/80±9/8 mmHg , and C/A reduced BP from 161/90±10/11 mmHg to 141/79±10/7 mmHg . The efficacy in reducing BP was similar between the two combination therapies . L/H significantly reduced serum potassium , but within the normal range , and did not increase serum uric acid or serum triglyceride . With L/H , the percentage of patients who attained the BP goal in SBP was higher in elderly patients than in younger patients . As L/H is more cost-effective than c and esartan/amlodipine and has fewer adverse effects on uric acid and other metabolic parameters than diuretic monotherapy , it is concluded to be useful for the management of hypertension BACKGROUND Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes . Approximately 30 % of type 1 patients with diabetic nephropathy ( DN ) have albuminuria > 1 g/day , and blood pressure > 135 and /or > 85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor ( ACEI ) and diuretics . We tested the effect of dual blockade of the renin-angiotensin system ( RAS ) in these patients . METHODS We performed a r and omised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d . and placebo added on top of previous antihypertensive treatment . We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics , as defined above . At the end of each treatment period , albuminuria , 24-h blood pressure and glomerular filtration rate ( GFR ) were measured . RESULTS Addition of 300 mg Irbesartan to the patients ' usual antihypertensive therapy induced a mean reduction in albuminuria of 37 % ( 95 % CI 20 - 49 , P<0.001 ) ; from 1574 mg/24 h ( 95 % CI 1162 - 2132 ) to 996 mg/24 h ( 95 % CI 699 - 1419 ) , a reduction in 24-h blood pressure of 8 mmHg systolic ( 95 % CI -2 to 18 ) and 5 mmHg diastolic ( 95 % CI 1 - 9 ) ( P=0.11 and 0.01 , respectively ) ( from placebo , mean ( SE ) 146 (4)/80 ( 2 ) mmHg ) . GFR remained unchanged . Serum potassium increased ( mean 4.3 to 4.6 mmol/l , P=0.02 ) . Intervention to reduce serum potassium was needed in two patients with GFR < 35 ml/min/1.73 m(2 ) . Otherwise the dual blockade with Irbesartan was safe and well tolerated . CONCLUSIONS Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy , including recommended doses of ACEI and diuretics We studied the effects of potassium supplementation ( 60 mmol/day ) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind , r and omized cross-over trial . There was a significant decrease in the orthostatic fall in systolic blood pressure ( SBP 33 + /- 5 mmHg to 16 + /- 9 mmHg , p less than 0.01 ) and in supine SBP ( 162 + /- 7 to 150 + /- 7 mmHg , p less than 0.01 ) between placebo and potassium phases . Supine diastolic and erect blood pressures were unchanged , though pulse rate showed a greater orthostatic increase ( 7 + /- 3 beats/min to 14 + /- 2 beats/min , p less than 0.05 ) following potassium therapy . No significant changes were seen in intracellular electrolytes , plasma renin activity , aldosterone levels or body weight . Seven patients reported symptomatic improvement with potassium , but none during the placebo phase . Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension Epidemiologic surveys , experimental studies in animals , and clinical trials in young and middle-aged patients with hypertension indicate that dietary potassium lowers blood pressure . The mechanism of the antihypertensive effect is not well defined . Variations in serum potassium within the physiologic range may directly affect vascular smooth muscle tone . Potassium may also influence the regulation of blood pressure through effects on sodium h and ling , aldosterone secretion , the renin/angiotensin system , renal kallikrein , eicosanoids , and atrial natriuretic peptide . This study was undertaken to confirm the blood pressure-lowering effect of potassium in older patients and to determine the mechanism of the antihypertensive effect . Twenty-two patients greater than or equal to 60 yr of age were admitted to a Clinical Research Unit for 8 days after a 2-wk period free of antihypertensive medication . Patients were placed on an isocaloric diet containing 200 mmol/day of Na+ , 70 mmol/day of K+ , and 500 mg/day of Ca2 + and were treated in a r and omized , double-blinded manner with either potassium chloride ( 120 mmol/day ) or placebo . After 4 days , patients were crossed over to the alternate treatment . Systolic blood pressure decreased 8.6 mm Hg ( 95 % confidence interval -14.6 , -2.6 ) , and diastolic blood pressure decreased 4.0 mm Hg ( -6.9 , -1.0 ) during potassium chloride supplementation . There was no significant change in blood pressure during treatment with placebo . Serum K+ was 3.9 + /- 0.1 mmol/L after 3 days of placebo and 4.3 + /- 0.1 after 4 days of potassium chloride ( P less than 0.002 ) . Urinary sodium excretion averaged 192 + /- 11 mmol/day after placebo and 221 + /- 8 after potassium treatment ( P less than 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Recent surveys reveal continuing deficiencies in the awareness , treatment , and control of hypertension . In many cases , failure to achieve blood pressure targets may be attributable to the use of antihypertensive monotherapy . OBJECTIVES This study was undertaken to identify combinations of telmisartan , a new oral angiotensin II type 1-receptor antagonist , and hydrochlorothiazide ( HCTZ ) that might provide greater antihypertensive efficacy than monotherapy with either agent in the treatment of mild to moderate hypertension . It also examined the dose-response surface for the 2 drugs alone and in combination . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , parallel-group study that employed all cells of a 4 x 5 factorial design . After a 4-week , single-blind , placebo run-in period , men and women between 18 and 80 years of age with mild to moderate hypertension ( defined as mean supine diastolic blood pressure [ DBP ] between 95 and 114 mm Hg during the last 2 weeks of the placebo run-in period and systolic blood pressure [ SBP ] between 114 and 200 mm Hg immediately before r and omization ) were eligible to enter the 8-week , double-blind , double-dummy treatment period . Study comparisons were between once-daily telmisartan monotherapy ( 20 , 40 , 80 , or 160 mg ) , HCTZ monotherapy ( 6.25 , 12.5 , or 25 mg ) , 12 combinations of these telmisartan/HCTZ doses , and placebo . The focus was on 2 combinations : telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg . The primary efficacy variable was change in supine trough DBP from baseline to the last evaluable measurement during double-blind treatment . Plasma renin activity and safety parameters , including treatment-emergent adverse events , physical findings , electrocardiograms , and serum electrolyte levels ( which are known to increase with HCTZ treatment ) , were also assessed . RESULTS Of 1293 patients screened , 818 ( 63.3 % ) were enrolled at 47 centers . Of these 818 , 749 ( 91.6 % ) completed the study . The intent-to-treat population ( r and omized with > or = 1 postr and omization blood pressure measurement ) consisted of 807 patients ( 98.7 % ) . Telmisartan 80 mg/HCTZ 12.5 mg significantly decreased mean supine trough SBP/DBP by 23.9/14.9 mm Hg , a benefit of 8.5/3.4 mm Hg compared with telmisartan 80 mg and of 17.0/7.6 mm Hg compared with HCTZ 12.5 mg ( both comparisons , P < 0.01 ) . Telmisartan 40 mg/HCTZ 12.5 mg significantly reduced mean supine SBP by 18.8 mm Hg , a benefit of 6.6 mm Hg compared with telmisartan 40 mg and 11.9 mm Hg compared with HCTZ 12.5 mg ( both , P < 0.01 ) . This same combination significantly reduced mean supine DBP by 12.6 mm Hg , a benefit of 5.3 mm Hg compared with HCTZ 12.5 mg ( P < 0.01 ) , but was not significantly different from telmisartan 40 mg . Telmisartan 80 mg/HCTZ 12.5 mg was significantly more effective than telmisartan 40 mg/HCTZ 12.5 mg in reducing mean supine DBP and SBP ( both , P < 0.05 ) . The response surface and responder analyses confirmed the additive antihypertensive efficacy of the combination of telmisartan and HCTZ . All regimens were well tolerated . CONCLUSIONS Once-daily telmisartan 80 mg/HCTZ 12.5 mg was effective and well tolerated when used to reduce SBP and DBP in patients with mild to moderate hypertension . In addition to enhancing efficacy , this combination protected against potassium depletion , a common side effect of thiazide monotherapy Abstract Background . Arterial hypertension is commonly associated with hyperuricemia . Several studies have shown that allopurinol reduces arterial blood pressure in animal models and in adolescent patients with newly diagnosed hypertension . Moreover , allopurinol has shown beneficial effects on endothelial function and arterial wave reflection in contrast to uricosuric agents . Antihypertensive drugs produce different effects on serum uric acid levels . Objective . The aim of the study was to evaluate the influence of allopurinol on blood pressure and aortic compliance in patients with arterial hypertension depending on hypotensive therapy with angiotensin-converting enzyme inhibitor ( ACE-I ) or thiazide diuretic , hypotensive drugs with distinct effects on serum uric acid levels and conversely , a positive influence on pulse wave velocity ( PWV ) in the aorta . Material and Methods . Sixty-six patients aged 25–70 ( mean age 46.17 ± 10.89 ) with mild and moderate arterial hypertension diagnosed on the basis of office blood pressure , were studied . They were r and omized to antihypertensive therapy on either perindopril ( n = 35 ) or hydrochlorothiazide ( n = 31 ) . After 8 weeks of antihypertensive therapy , 150 mg of allopurinol daily was added for the next 8 weeks . Measurement of the serum uric acid level , PWV and 24-h ambulatory blood pressure monitoring ( ABPM ) were performed at baseline , after 8 weeks antihypertensive therapy and again after the final 8 weeks with the additional allopurinol . Results . No significant changes in systolic ( SBP ) and diastolic blood pressure ( DBP ) or ABPM were observed after allopurinol treatment in either of the subgroups receiving ACE-I or thiazide-based antihypertensive therapy . The mean PWV decreased from 10.7 ± 1.4 m/s to 10.0 ± 1.2 m/s ( p = 0.00008 ) in the ACE-I-based therapy subgroup and from 11.5 ±1.7 m/s to 10.4 ± 1.5 m/s ( p = 0.00002 ) in the thiazide-based therapy subgroup after treatment with allopurinol . However , significant correlations were found between PWV changes and the basic PWV ( r = −0.52 ; p < 0.001 ) or SBP changes ( r = 0.29 ; p < 0.019 ) after allopurinol treatment . Conclusions . Allopurinol does not produce additional antihypertensive effects in patients with treated arterial hypertension . Allopurinol increases aortic compliance independently of ACE-I or thiazide-based , antihypertensive therapy . However , this effect is significantly dependent on the initial PWV in the aorta and on SBP changes during allopurinol therapy Background : Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction ; however , they are not widely used due to risk of hyperkalemia . This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease ( CKD ) and resistant hypertension whose blood pressure ( BP ) is reduced to a guideline goal . Methods : This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists . Forty-six patients with resistant hypertension and stages 2 or 3 CKD ( mean estimated glomerular filtration rate ( eGFR ) 56.5 ± 16.2 ml/min/1.73 m2 ) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens . All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker . Patients were evaluated after a median of 45 treatment days . The primary endpoint was change in systolic BP . Secondary endpoints included change in serum potassium , creatinine , eGFR , diastolic BP and tolerability . Results : The mean age of the patients studied was 64.9 ± 10.7 years , all were obese and 86 % had type 2 diabetes , with 82 % being African-American . Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg ( p = 0.001 ) . Females with BMI > 30 and those with a baseline systolic BP > 160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism . In total , 39 % of the patients had a > 30 % decrease in eGFR when the BP goal was achieved . The mean increase in serum potassium was 0.4 mEq/l above baseline ( p = 0.001 ) , with 17.3 % manifesting hyperkalemia , i.e. serum potassium > 5.5 mEq/l . Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m2 in whom serum potassium was > 4.5 mEq/l on appropriately dosed diuretics . Contributing risks in this subgroup included a systolic BP reduction of > 15 mm Hg associated with an eGFR fall of > 30 % . Conclusion : Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic . Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of > 4.5 mEq/l for safety reasons Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer 's disease ( AD ) , it remains unclear which class provides the most benefit . The Cache County Study of Memory Health and Aging is a prospect i ve longitudinal cohort study of dementing illnesses among the elderly population of Cache County , Utah . Using waves I to IV data of the Cache County Study , 3417 participants had a mean of 7.1 years of follow-up . Time-varying use of antihypertensive medications including different class of diuretics , angiotensin converting enzyme inhibitors , β-blockers , and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses . During follow-up , 325 AD cases were ascertained with a total of 23,590 person-years . Use of any antihypertensive medication was associated with lower incidence of AD ( adjusted hazard ratio [ aHR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.61 - 0.97 ) . Among different classes of antihypertensive medications , thiazide ( aHR , 0.7 ; 95 % CI , 0.53 - 0.93 ) , and potassium-sparing diuretics ( aHR , 0.69 ; 95 % CI , 0.48 - 0.99 ) were associated with the greatest reduction of AD risk . Thiazide and potassium-sparing diuretics were associated with decreased risk of AD . The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort , now with longer follow-up , and merits further investigation
Differences in antihypertensive effect were due to potency rather than efficacy .
This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines
BACKGROUND Potassium-sparing diuretics ( PSDs ) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure ( SBP ) .
However , their key parameters affecting SBP and serum potassium are poorly defined , fostering underutilization .