Potassium supplementation fails to lower blood pressure in hypertensive patients receiving a potassium losing diuretic. Effect of potassium supplementation combined with dietary sodium reduction on blood pressure in men taking antihypertensive medication The Combination of Chlorthalidone with Nifedipine Does Not Exert an Additive Antihypertensive Effect in Essential Hypertensives: A Crossover Multicenter Study Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension. TAIM Research Group. Trial of Antihypertensive Interventions and Management. Effect of Drug and Diet Treatment of Mild Hypertension on Diastolic Blood Pressure Central versus peripheral blood pressure in malignant hypertension; effects of antihypertensive treatment. Potassium supplementation in the treatment of idiopathic postural hypotension. Potassium supplementation in hypertensive patients with diuretic-induced hypokalemia. Potassium supplementation reduces clinic and ambulatory blood pressure in elderly hypertensive patients The effect of chlorthalidone on ventricular ectopic activity in patients with isolated systolic hypertension. The SHEP Study Group. Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial. Increasing the dietary potassium intake reduces the need for antihypertensive medication. Potassium supplementation in blacks with mild to moderate essential hypertension. Potassium effects on blood pressure: is the conjugate anion important? Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study. Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention.
Thirty-three patients with hypertension receiving drug treatment that included a potassium losing diuretic were r and omly allocated to 64 mmol of potassium  ( 14 patients ) or to no additional potassium supplementation  ( 19 patients ) . Potassium was administered as slow release potassium chloride . After 3 months , blood pressure fell by 5/1 mm Hg in the patients who received the supplements and by 7/4 mm Hg in those who did not receive them . The falls in pressure were not significantly different and the 90 % confidence limits for the effect of supplementation on diastolic pressure were : a fall of 2 mm Hg and a rise of 11 mm Hg , thus excluding an important hypotensive effect in these patients . Conversely , plasma creatinine fell by 11 % in the supplement group compared with a 6 % rise in the control group ( P less than 0.05 ) . Potassium supplementation , either by pharmacological preparations or by dietary manipulation , may prove to be desirable in patients on a potassium losing diuretic but should not be expected to lower blood pressure in such patients It has long been suspected that sodium and potassium intake influence blood pressure . Since both these electrolytes can be modified by diet , attention has focused on decreasing sodium intake and increasing potassium intake as a potential way of treating and preventing hypertension .  Several short-term controlled clinical trials have examined the effect of supplemental potassium intake on blood pressure , but with inconsistent results [ 1–8 ] . The Minnesota Mount Sinai Hypertension Trial ( MSHT ) is a double-blind study comparing placebo with potassium supplementation for controlling blood pressure in hypertensive men on a sodium-restricted diet over a 2–3 year follow-up period . At the time of r and omization to placebo or supplemental potassium and through 12 weeks of follow-up , the patients were  taking antihypertensive medication .  This preliminary report compares blood pressure changes between the placebo and supplemental potassium groups over the first 12 weeks of the trial To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment , 66 uncomplicated essential hypertensives , whose diastolic blood pressure was > 100 and < 115 mm Hg at the end of a 1-month washout placebo period , received , according to a r and omized , double-blind , crossover design , nifedipine ( 20 mg b.i.d . ) , chlorthalidone ( 25 mg o.d . ) , the two drugs combined at the same doses , and the corresponding placebo . When compared to the r and omized placebo the three active treatments significantly ( p < 0.001 ) reduced blood pressure without changing heart rate and body weight . However , blood prssure values were similarly reduced under nifedipine and the combination and were significantly lower ( p < 0.05 ) than those under chlorthalidone . Moreover , the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly ( normalized , p < 0.001 ; responders , p < 0.02 ) greater than those under chlorthalidone . Under chlorthalidone and its combination with nifedipine , plasma potassium tended to decrease and blood glucose and serum uric acid were significantly ( p < 0.05 ) increased . These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid . Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives The Trial of Antihypertensive Interventions and Management ( T AIM ) was a multicenter r and omized drug ( double-blind , placebo-controlled)-diet trial . One objective of T AIM was to assess the long-term ability of a low-sodium/high-potassium ( Na+ decreases/K+ increases ) diet to maintain blood pressure control in persons at 110 % to 160 % ideal weight with diastolic blood pressure from 90 to 100 mm Hg who were on no drugs or on low-dose monotherapy . Participants , 56 % men and 33 % black , were r and omized to usual diet  ( n = 296 ) or to Na+ decreases/K+ increases diet  ( n = 291 ) and within each diet group to placebo , 25 mg/day chlorthalidone , or 50 mg/day atenolol . Treatment failure was defined as lack of blood pressure control requiring additional drugs according to specified criteria . At baseline , the mean value for age was 48 years ; blood pressure , 143/93 mm Hg ; weight , 88 kg ; and 24-h urinary sodium and potassium excretion rates , 133 and 57 mmol/day , respectively . At 3 years , the net difference in 24-h urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases and the usual diet groups was -30 and + 11 mmol/L/day . The relative risk of treatment failure for Na+ decreases/K+ increases compared to usual diet by proportional hazards regression was 0.95 ( P = .71 ) . This study provides no support for the sole use of a low-sodium/high-potassium diet as a practical therapeutic strategy in maintaining blood pressure control in the moderately obese The Trial of Antihypertensive Interventions and Management is a multicenter r and omized trial design ed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mm Hg ) . Eight hundred and seventy-eight participants at 110 - 160 % of ideal weight were r and omly allocated to nine drug/diet treatment groups receiving either a placebo , chlorthalidone ( 25 mg ) , or atenolol ( 50 mg ) , combined with a usual , a weight loss , or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months . Seven hundred and eighty-seven participants had follow-up data . The mean baseline diastolic blood pressure  was 93.8 mm Hg ; 55.9 % of the participants were male , and the weight loss diet group lost an average of 4.7 kg . Multiple comparisons were accounted for in the analysis . A significantly greater lowering of diastolic blood pressure ( 12.4 mm Hg ) was achieved in the atenolol group compared with either the low sodium/high potassium diet group ( 7.9 mm Hg , p=0.001 ) or weight loss group ( 8.8 mm Hg , p=0.006 ) . Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering ( 15.1 mm Hg ) when compared with the diuretic alone ( 10.8 mm Hg , p=0.002 ) , but adding a low sodium/high potassium diet ( 12.2 mm Hg , p=0.029 ) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration , drugs outperform diet , and weight loss is beneficial , especially with diuretics BACKGROUND Sodium nitroprusside ( SNP ) and labetalol are recommended for the immediate treatment of malignant hypertension . Both are intravenous agents but have different effects on systemic hemodynamics , and may have differential effects on pulse-wave reflection and pulse-pressure amplification , with consequences for peripheral versus central blood pressures ( BPs ) . METHODS We conducted a nonr and omized , open-label study of 8 patients treated with sodium nitroprusside ( mean age ( ±SD ) , 44±14 years ; 6 males ; diastolic/systolic BP , 225±22/135±8 mm Hg ) and 6 patients treated with intravenous labetalol ( mean age , 39±15 years ; 4 males ; systolic/diastolic BP , 232±22/138±17 mm Hg ) before and after treatment for malignant hypertension , aim ing at a 25 % reduction in mean arterial pressure . We measured peripheral pressures with an intra-arterial catheter in the radial artery and derived central pressures with a generalized transfer filter . RESULTS Mean arterial pressure was similarly reduced with sodium nitroprusside and labetalol ( by 27 % and 30 % , respectively ; P = 0.76 ) . There was a nonsignificantly greater reduction in peripheral systolic blood pressure ( SBP )  with labetalol than with sodium nitroprusside ( 29±11 % vs. 18±7 % , P = 0.08 ) . The decline in peripheral diastolic blood pressure ( DBP ) with the two agents was comparable , whereas the reduction in peripheral pulse pressure was 8±16 % with SNP and 33±17 % with labetalol ( P = 0.01 ) . The decline in reflection magnitude was greater with SNP than with labetalol . There were no significant differences in the reduction of central BP  with SNP and labetalol . The amplification of PP increased with SNP but did not change with labetalol . CONCLUSIONS We found no difference in central SBP or PP in subjects treated with SNP and labetalol , but labetalol produced a greater reduction in peripheral SBP and PP in the immediate treatment of malignant hypertension 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 Changes in potassium balance have been found to have variable effects on the blood pressure of animals , and the administration of potassium supplements has been reported to lower the blood pressure of normokalemic hypertensive patients . To assess the effect of potassium repletion in hypokalemic hypertension , we administered either potassium chloride , 60 mmol per day , or placebo tablets , each for six weeks , in a r and omized , double-blind , crossover trial to 16 hypertensive patients who had diuretic-induced hypokalemia and who continued to take a constant amount of diuretic . We selected patients whose control serum potassium levels were below 3.5 mmol per liter . In association with an average rise in the serum potassium concentration of 0.56 mmol per liter , the mean blood pressure fell by an average of 5.5 mm Hg ( P = 0.004 ) , with at least a 4 mm Hg fall observed in 9 of the 16 patients . The fall in blood pressure correlated with a fall in plasma renin activity ( r = 0.568 , P = 0.043 ) but not with changes in plasma aldosterone levels or other variables . We conclude that short-term potassium supplementation that ameliorates diuretic-induced hypokalemia may induce a significant fall in blood pressure Objectives : To determine the effects of potassium chloride 60 mmol/day supplementation on clinic and 24-h ambulatory blood pressure values in elderly untreated hypertensive patients Design : A double-blind r and omized placebo-controlled crossover study lasting 8 weeks , following a 4-week run-in period Setting : Outpatient clinic in a district general hospital Patients : Eighteen untreated elderly hypertensive patients ( mean age 75 years , range 66—79 ) with a systolic blood pressure of ≥160mmHg and /or a diastolic blood pressure of ≥95mmHg were recruited from the clinics of local general practitioners and from the current hospital outpatient department . Patients had not received any antihypertensive medication for at least 4 weeks before entry into the study Interventions : Before entry into the study , the daily dietary electrolyte intake of each individual was established and this was maintained during the run-in and intervention periods . Following a 4-week run-in period patients received potassium supplements or matching placebo , each for 4 weeks Main outcome measures : The within-patient changes in clinic and 24-h ambulatory blood pressures at the end of each intervention period . Results : After 4 weeks potassium supplementation compared with placebo there was a significant fall in supine clinic blood pressure , st and ing and 24-h ambulatory systolic blood pressure . There was no significant change in clinic st and ing diastolic blood pressure , 24-h ambulatory diastolic blood pressure or pulse rate . Plasma renin activity increased and body weight fell after potassium supplementation . Twenty-four-hour urinary potassium rose significantly , whereas urinary sodium excretion was unchanged Conclusions : A 60-mmol daily supplement of potassium chloride  reduces clinic and 24-h ambulatory blood pressure in elderly hypertensive In an ancillary study of the Systolic Hypertension in the Elderly Program ( SHEP ) , the effects of diuretics on ventricular ectopic activity were investigated in 186 patients with isolated systolic hypertension .  Ventricular premature complexes ( VPCs ) were examined as the number of VPCs/24 hours , presence of > or = 1 VPC , presence of > or = 10 VPCs/24 hours , and presence of VPC pairs or ventricular tachycardia . Significant changes in VPCs were not observed either in the 92 patients r and omized to chlorthalidone stepped-care ( 12.5 and 25 mg/day ) or in the 94  placebo-treated patients ( p > 0.1 for all VPC definitions and both groups ) . Serum potassium decreased from 4.4 + /- 0.5 to 4.1 + /- 0.5 mEq/liter ( p = 0.002 ) in the chlorthalidone group and did not change ( 4.4 + /- 0.5 to 4.5 + /- 0.4 mEq/liter ) in the placebo group . Potassium was prescribed routinely for confirmed hypokalemia < 3.5 mEq/liter . A relation between serum potassium and VPC or change in serum potassium and change in VPC was not observed in the chlorthalidone group . In summary , in patients with isolated systolic hypertension , chlorthalidone in doses that are effective in decreasing stroke and cardiovascular event rates ( 12.5 or 25 mg/day ) , did not increase VPCs Isolated systolic hypertension is common in the elderly , but decreasing systolic blood pressure ( SBP ) without lowering diastolic blood pressure ( DBP ) remains a therapeutic challenge . Although stress management training , in particular eliciting the relaxation response , reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated . We conducted a double-blind , r and omized trial comparing 8 weeks of stress management , specifically relaxation response training ( 61 patients ) , versus lifestyle modification ( control , 61 patients ) . Inclusion criteria were > or=55 years , SBP 140 - 159 mm Hg , DBP < 90 mm Hg , and at least two antihypertensive medications . The primary outcome measure was change in SBP after 8 weeks . Patients who achieved SBP < 140 mm Hg and > or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination . SBP decreased 9.4 ( st and ard deviation [ SD ] 11.4 ) and 8.8 ( SD 13.0 ) mm Hg in relaxation response and control groups , respectively ( both ps < 0.0001 ) without group difference ( p=0.75 ) . DBP decreased 1.5 ( SD 6.2 ) and 2.4 ( SD 6.9 ) mm Hg ( p=0.05 and 0.01 , respectively ) without group difference ( p=0.48 ) . Forty-four ( 44 ) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination . After controlling for differences in characteristics at the start of medication elimination , patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication ( odds ratio 4.3 , 95 % confidence interval 1.2 - 15.9 , p=0.03 ) . Although both groups had similar reductions in SBP , significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control OBJECTIVE To determine whether an increase in dietary potassium intake from natural foods reduces the need for antihypertensive medication in patients with essential hypertension . DESIGN R and omized , controlled trial with 1-year follow-up . SETTING Hypertension outpatient clinic of a university hospital . PATIENTS Fifty-four patients with well-controlled hypertension , 47 of whom completed 1 year of follow-up . INTERVENTION Patients were r and omly assigned to one of two groups and were given dietary advice aim ed at selectively increasing potassium intake ( group 1 ) or at keeping their customary diet unchanged ( group 2 ) . During a 1-year follow-up period , drug therapy was reduced in stepwise fashion , according to a fixed protocol , provided that blood pressure remained below 160/95 mm Hg . MAIN RESULTS Potassium intake was checked monthly by referring to 3-day food records and by measuring 24-hour urinary potassium excretion . Potassium intake increased in group 1 but did not change in group 2 ( P less than 0.001 ) . No change was observed in either urinary sodium excretion or in body weight . After 1 year , the average drug consumption ( number of pills per day ) relative to that at baseline was 24 % in group 1 ( 95 % Cl , 15 % to 32 % ) and 60 % in group 2 ( Cl , 44 % to 76 % ) ( P less than 0.001 ) . By the end of the study , blood pressure could be controlled using less than 50 % of the initial therapy in 81 % of the patients in group 1 ( Cl , 66 % to 96 % ) compared with 29 % of the patients in group 2 ( Cl , 10 % to 48 % ) ( P = 0.001 ) . Patients in group 1 ended the study with a lower number of reported symptoms compared with patients in the control group ( P less than 0.001 ) . CONCLUSION Increasing the dietary potassium intake from natural foods is a feasible and effective measure to reduce antihypertensive drug treatment Potassium chloride ( KCl ) salt ( 65 mmol ) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study . The fall in BP was independent of the order of r and omization and was significant for systolic ( SBP ; P less than 0.01 ) and diastolic ( DBP ; P less than 0.05 ) pressure after 4 weeks . Analysis of the 95 % confidence intervals in this and in five other studies , two of which were reported as showing no beneficial effect , suggests that potassium supplementation does lower BP , but that the change is small and within the confidence levels of all six trials . Thus , apparent discrepancies in the literature are not genuine statistically Potassium salts , often in the form of KCl , have had variable hypotensive effects in experimental animals and man . The chloride anion has recently been implicated as the hypertensive agent in salt-sensitive hypertension . We therefore hypothesized that non-chloride salts of potassium would have superior hypotensive effects to KCl . In r and omized , double-blind fashion , we administered placebo , KCl ( 75 mmol/day ) or potassium citrate ( 75 mmol/day ) to 24 normotensive adult males . In these subjects , neither KCl nor potassium citrate affected blood pressure , despite urinary verification of potassium supplement intake . Thus , in these experimental circumstances , neither potassium nor its conjugate anion were of importance in lowering blood pressure 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 To determine whether the combination of nifedipine + chlorthalidone exerts an additive antihypertensive effect when compared with single-drug treatment , we studied 66 uncomplicated essential hypertensives , with diastolic blood pressure of greater than 100 and less than 115 mmHg . At the end of a 1-month washout placebo period , using a double-blind crossover design , the patients were r and omly allocated to nifedipine ( 20 mg twice a day ) , chlorthalidone ( 25 mg once a day ) , the two drugs combined at the same doses and the corresponding placebo . Compared with the r and omly allocated placebo , the three active treatments significantly reduced blood pressure without changing the heart rate or body weight . Both the absolute and percentage decreases in mean blood pressure induced by nifedipine and the combination compared with placebo were similar and significantly greater than those induced by chlorthalidone . Taken together , these data show that the combination of nifedipine + chlorthalidone does not exert any additive antihypertensive effect compared with nifedipine alone . This finding indicates that the combination of a dihydropyridine calcium antagonist + a thiazide diuretic is probably devoid of any particular clinical significance in the treatment of uncomplicated essential hypertensives The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive , moderately obese participants using a 3 x 3 factorial design . Drugs evaluated were placebo , diuretic ( chlorthalidone ) , and beta-blocker ( atenolol ) ; diets were usual ( no intervention ) , weight reduction , and low sodium/high potassium ( Na/K ) . This article reports 6-month dietary changes and the effect of dietary change on blood pressure . Six-month mean weight change was -4.7 kg in the weight reduction group , -0.3 kg in the Na/K group , and -0.5 kg in the usual-diet group . At 6 months , daily electrolyte excretion had changed in the Na/K intervention group . Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group . Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group , from 57.0 to 60.5 mmol in the weight reduction group , and from 55.3 to 59.1 mmol in the usual diet group . Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol . Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification
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 .