Aldosterone escape with diuretic or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy in patients with mild to moderate hypertension

Renin-angiotensin-aldosterone system (RAAS) hyperactivity is implicated in the development of hypertension and progressive damage in target organs. Chronic inhibition of the RAAS or use of thiazide-type diuretics may trigger an aldoster-one escape. The aim of this study was to assess this phenomenon in hypertensive patients treated with thiazide-type diuretics (hydrochlorothiazide [HCTZ]) or single or double blockade of the RAAS (irbesartan [IRBE], quinapril [QUIN], and IRBE+QUIN). Blood pressure levels were obtained by 24-hour ambulatory blood pressure monitoring. Plasma renin activity and aldosterone levels were determined by immunoradiometric assay. Blood pressure level was normalized in the 4 treatment groups; the HCTZ and IRBE+QUIN groups showed an increased plasma aldosterone level after 12 weeks (9.1+/-2.2 to 14.1+/-1.4 and 6.9+/-1.9 to 12.9+/-2.3 ng/dL, respectively; P<.05), whereas plasma renin activity was increased only in the HCTZ group (0.9+/-0.2-1.7+/-0.2 ng/mL/h; P<.05). The increase in plasma aldosterone level after 12 weeks of HCTZ and IRBE+QUIN therapy suggests early aldosterone escape.     

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.     

Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy

OBJECTIVE: To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy. DESIGN AND METHODS: Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period. RESULTS: Sixty-four individuals completed the study: 32 men and 32 women (mean +/- SD age 48.2 +/- 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 +/- 12.6/87.7 +/- 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 +/- 8.8/6.3 +/- 6.7 mmHg), amlodipine (15.2 +/- 12.9/9.9 +/- 6.8 mmHg) and chlorthalidone (13.5 +/- 11.6/9.5 +/- 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril. CONCLUSIONS: In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB-diuretic and the ARB-calcium antagonist combinations were superior to that of the ARB-ACE inhibitor combination.     

Effectiveness of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on atrial natriuretic peptide.

The aim of this study was to evaluate the effectiveness of an angiotensin-converting enzyne inhibitor (ACEI, quinapril) or angiotensin II receptor blocker (ARB, candesartan) on atrial natriuretic peptide (ANP) activity in rats with hypertension induced by nitric oxide (NO) inhibition. ACEI and ARB have a number of pharmacologic effects, including blood pressure reduction, myocardial preservation, and an unknown effect in the circulation. The changes in ANP in NO inhibitor-induced hypertensive rats were evaluated in order to elucidate the interaction between ANP and NO in the regulation of blood pressure. Thirty-six rats were divided into 4 groups and administered the experimental agents for 8 weeks: group Control was given regular food (n=9), group N(G)-nitro-L-arginine (L-NNA) was administered L-NNA (25 mg. kg(-1). day(-1), n=9), group ACEI was administered L-NNA and quinapril (10 mg. kg(-1). day(-1), n=9), and group ARB was administered L-NNA and candesartan (10 mg. kg(-1). day(-1), n=9). Blood pressure, plasma ANP, atrial ANP, ANP mRNA, and ANP granules were measured. A significant elevation in blood pressure was observed in group L-NNA. However, there were no increases in plasma ANP (L-NNA: 138.8+/-64.4, Control: 86.7+/-36.4), ANP mRNA (L-NNA: 2.2+/-1.0, Control: 1.7+/-0.5) or ANP granules (L-NNA: 61.1+/-10.2, Control: 64.5+/-8.5). No increase in blood pressure was seen in groups ACEI and ARB. However, plasma ANP (ACEI: 1,392.3+/-1,034.4, ARB: 1,142.8+/-667.3), ANP mRNA (ACEI: 52.8+/-29.1, ARB: 42.9+/-21.2), and ANP granules (ACEI: 122.5+/-23.4, ARB: 136.3+/-33.2) increased significantly. NO inhibitor-induced hypertension caused no changes in ANP concentrations. However, the ACEI and ARB had a direct effect on the induction of ANP secretion. The findings suggest that ANP secretion is directly effected by ACEI and ARB, which seems to play a key role in lowering blood pressure, relieving heart failure symptoms, and preserving the myocardium.     

Differential blood pressure reductions by angiotensin receptor blocker plus calcium channel blocker or diuretic in elderly hypertension with or without obesity

We conducted the Miyazaki Olmesartan Therapy for Hypertension in the EldeRly (MOTHER) study, which suggested that there are preferable effects of an angiotensin receptor blocker (ARB), olmesartan, plus a calcium channel blocker (CCB) over the ARB plus a diuretic, in elderly patients with hypertension. In this subanalysis, we examined whether obesity influences the efficacies of these combination therapies. The study subjects were 58 hypertensive patients ages 65 to 85, who had been randomly assigned to either group treated with olmesartan plus a CCB or a diuretic and completed the treatment for 6 months. Systolic and diastolic blood pressures were reduced following these combination treatments in nonobese and obese patients. In the CCB combination, blood pressure reductions in nonobese patients were larger than in obese patients at 1 and 3 months, and serum creatinine remained unchanged despite the greater reduction of blood pressure. Meanwhile, such differences were not noted in the diuretic groups. Plasma aldosterone was significantly reduced in nonobese patients of two combination groups, but not in those with obesity. ARB plus CCB combination therapy might be preferably chosen for nonobese elderly patients, whereas the influence of obesity seems smaller in the efficacy of ARB plus a diuretic.     

Rationale for the use of combination angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy in heart failure

BACKGROUND: Heart failure (HF) is a major cause of morbidity and mortality in the United States. The renin-angiotensin system (RAS) plays a major role in its pathophysiology, and angiotensin-converting enzyme (ACE) inhibitors are the cornerstone of therapy. However, HF continues to progress despite this therapy, perhaps because of production of angiotensin II by alternative pathways, which lead to direct stimulation of the angiotensin II receptor. Angiotensin II receptor blocker (ARB) therapy alone or in combination with the ACE inhibitor is a promising approach to block the RAS and slow HF progression more completely. METHODS: The current medical literature on the pathophysiology of HF and the use of ACE inhibitors and ARBs was extensively reviewed. RESULTS: Evidence from basic science, experimental animals, and clinical trials provides data on the safety and efficacy of RAS inhibition with ACE inhibitors and ARBs as monotherapy and in combination. Data from the Evaluation of Losartan in the Elderly (ELITE) II trial indicate that ARBs alone do not appear to be more effective than ACE inhibitors in HF, but studies evaluating their use in combination are currently ongoing. CONCLUSIONS: The addition of an ARB offers more complete angiotensin II receptor blockade of the RAS than can be obtained by ACE inhibitors alone. Combination therapy preserves the benefits of bradykinin potentiation offered by ACE inhibitors while providing potential antitrophic influences of AT(2) receptor stimulation and may play an increased role in the treatment of chronic HF in the future.     

Effects of angiotensin-converting enzyme inhibition on blood pressure and plasma renin activity in essential hypertension

Oral converting enzyme inhibitor SQ14225 was administered in 11 patients with essential hypertension, in order to investigate the role of the renin-angiotensin system in the regulation of blood pressure in essential hypertension. In the sodium-repleted state (150 mEq sodium intake for 6 days) in 11 patients, converting enzyme inhibitor decreased the average mean blood pressure from 113 +/- 2 to 106 +/- 2 mm Hg (p less than 0.001). Plasma renin activity increased with sodium depletion (30 mEq sodium intake for 3 days after furosemide treatment) from 1.26 +/- 0.07 to 3.26 +/- 0.48 ng/ml/hr (p less than 0.001). In the sodium-depleted state the hypotensive effect of SQ 14225 was more pronounced (mean blood pressure 108 +/- 2 to 93 +/- 3 mm Hg). The decrease in mean blood pressure caused by the inhibitor correlated to the basal plasma renin activity (r = -0.53, p less than 0.02, n = 22 measurements). The results indicate that the renin-angiotensin system participates in the regulation of blood pressure in essential hypertension, even in the sodium-repleted state. This role of the renin-angiotensin system in blood pressure regulation becomes more crucial during sodium depletion.     

Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure.

BACKGROUND: The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone. METHODS AND RESULTS: One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were randomly assigned to the combination therapy or monotherapy. Changes in physical activity (New York Heart Association functional classes, Specific Activity Scale (SAS)), concentrations of neurohumoral factors (plasma renin activity, angiotensin II, aldosterone, and brain natriuretic peptide (BNP)), and cardiac function for 6 months were compared between the 2 groups. It was found that the combination therapy, which was administered at doses standard in Japan, increased the SAS score (4.5 +/- 1.5 to 4.9 +/- 1.5, p<0.05) and decreased the plasma BNP concentration (183 +/- 163 to 135 +/- 118 pg/ml, p<0.05). In contrast, there were no changes in SAS score (4.5 +/- 1.4 to 4.6 +/- 1.4, NS) or BNP concentration (156 +/- 157 to 151 +/- 185 pg/ml, NS) in the patients receiving monotherapy. CONCLUSIONS: The results of the study demonstrate that the combination therapy, even at the standard doses for Japan, improves physical activity and plasma BNP concentration more than the monotherapy. A larger study is required to assess the effects of the combination therapy on major clinical outcomes.     

Interaction between an angiotensin converting enzyme inhibitor, perindopril, and a thiazide diuretic in the spontaneously hypertensive rat.

Fifty adult male spontaneously hypertensive rats were randomly allocated to receive daily oral treatment with placebo, hydrochlorothiazide (HCTZ 10 mg/kg) and three different dosages of perindopril (S9490-30.1, 0.3 and 1 mg/kg) administered alone or in combination with HCTZ for two eight-day treatment periods separated by a therapeutic washout period of 13 days. Effect of order of treatment was evaluated in rats receiving perindopril plus HCTZ. Time course of changes in systolic blood pressure, heart rate, 24 h urine volume and urinary excretion of sodium, potassium and chloride were studied and compared for all groups. HCTZ alone and lower dosages of perindopril (0.1 mg/kg, 0.3 mg/kg) were ineffective in lowering elevated systolic blood pressure of the spontaneously hypertensive rat, and there were no significant intergroup differences in urine volume and electrolytes. However, antihypertensive efficacy of lower dosages of perindopril was significantly (P less than 0.01) enhanced when administered in combination with HCTZ. The combined treatment also induced significant (P less than 0.01) diuresis and urinary chloride excretion. No significant effect was seen in heart rate. The dose-effect relationship of the combination confirmed the existence of synergistic antihypertensive action between HCTZ and perindopril in the spontaneously hypertensive rat.     

Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy: its role in clinical practice

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly prescribed for the management of hypertension. In addition, each of these drug classes has been shown to be effective in the treatment of congestive heart failure, proteinuric chronic kidney disease, and most recently the high-cardiac-risk profile patient. The individual success of each of these drug classes has fueled the theory that given together, the overall biologic effect of both would surpass that of either given alone. The foundation of this premise, although biologically plausible, has yet to be proven in a compelling enough fashion to support the everyday use of these two drug classes in combination. Additional clarifying studies are required to establish whether specific patient subsets exist that might benefit from such combination therapy.     

Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

Lack of effect on coronary atherosclerotic disease biomarkers with modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type-1 receptor blocker, and the combination

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, used alone or in combination, have been shown to improve outcomes in certain populations, primarily when administered in high doses. For stable coronary atherosclerotic disease, however, the relative physiologic effect of these therapies is unclear. Furthermore, because of the notorious subtarget dosing of such agents in clinical practice, we explored the influence of a modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blockers, and the combination on common biologic markers of coronary atherosclerotic disease. METHODS: This randomized, cross-over study enrolled stable coronary atherosclerotic disease patients (n=20), each receiving three treatments: candesartan 16 mg daily, ramipril 5 mg daily, and candesartan 8 mg plus ramipril 2.5 mg daily. Treatments were administered for 2 weeks with a 2-week washout. Blood samples were collected before and after each treatment. Markers of endothelial function, fibrinolytic balance, and vascular inflammation were measured. RESULTS: No significant differences were observed in the pretreatment concentrations of angiotensin-converting enzyme or of any measured biologic marker. Relative to pretreatment levels, candesartan alone was the only therapy to exhibit an action on any measured biomarker--a trend toward increased nitric oxide concentrations (P=0.054). Otherwise, no effects on biologic markers were observed with the treatments. CONCLUSION: This study of various methods of the renin-angiotensin system inhibition in stable coronary atherosclerotic disease patients demonstrates negligible effects of a modest dosing of ramipril and the combination of ramipril plus candesartan on common biologic markers of coronary atherosclerotic disease. Candesartan at modest doses may favorably influence endothelial function. Overall, however, the results indicate that the commonly practiced subtarget dosing of such treatments provides little, if any, benefit pertaining to key physiologic components of coronary atherosclerotic disease.     

Reporting on sex-based analysis in clinical trials of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker efficacy

BACKGROUND:

Clinical practice recommendations for hypertension do not make recommendations specific to men or women. However, the sex hormones appear to modulate differently the renin-angiotensin system (RAS), which plays a central role in the regulation of blood pressure. Today, little is known about the effects of sex on the efficacy of therapies that antagonize the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).

OBJECTIVE:

To identify randomized controlled trials evaluating the efficacy of ACEIs and ARBs in preventing major cardiovascular outcomes, determine what proportion of the trial participants were female, and evaluate whether there was any evidence of a sex difference in the efficacy of these agents.

METHODS:

A systematic review of the literature was conducted to identify randomized controlled trials that used either ACEIs or ARBs for the treatment of hypertension.

RESULTS:

Thirteen ACEI trials and nine ARB trials were identified. Sex-specific outcome data were available in six of the ACEI trials and three of the ARB trials. These trials enrolled 74,105 patients; 39.1% were women. Seven of the nine trials indicated that ACEIs or ARBs may be slightly more beneficial in men. The magnitude of these differences, in most trials, was small.

CONCLUSIONS:

Sex-specific data are reported in 43% of large hypertension clinical trials. Review of the trials reporting sex-specific effect sizes indicates that ACEIs and ARBs may be more effective in men.     

Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker.

Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p<0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p<0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.     

Combination therapy with an angiotensin-converting enzyme inhibitor and a calcium channel blocker

More than 1 medication is required in many hypertensive patients to reach blood pressure (BP) goals, and initial treatment with 2 agents has been recommended for patients whose BP level is >20/10 mm Hg above target. Diuretics reduce BP levels and the incidence of target organ complications and together with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers, which are recommended in patients with comorbid cardiovascular disease, nephropathy, or diabetes, are effective antihypertensive combinations. Calcium channel blockers (CCBs) are also effective antihypertensive agents, and evidence suggests that a CCB/ACEI combination is well tolerated and also decreases the risk of cardiovascular and renal disease. Some evidence suggests that this combination may improve endothelial function more than either agent alone, and its use could potentially lead to better cardiovascular outcomes than a diuretic/ACEI or diuretic/ARB combination. The ongoing Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial compares these 2 effective combinations (ie, an ACEI/diuretic and ACEI/CCB) as initial treatment for reducing cardiovascular morbidity and mortality in older high-risk hypertensive patients. The results of this trial, when reported, should help to clarify the relative benefits of these different therapies.     

Intraindividual blood pressure responses to angiotensin-converting enzyme inhibition and angiotensin receptor blockade

This study aims to test the hypothesis that in some hypertensive subjects the blood pressure (BP) response to angiotensin-converting enzyme inhibition differs from that to angiotensin receptor blockade (ARB); a responder to angiotensin-converting enzyme inhibition may not respond to ARB or the opposite. A randomized, open-label, crossover, comparative trial of lisinopril 20 mg compared with telmisartan 80 mg (5 weeks per treatment period) was conducted in 32 untreated hypertensives using 24-hour ambulatory BP monitoring. Subjects were classified as "responders" and "nonresponders" using an arbitrary threshold of ambulatory BP response (> or =10 mm Hg systolic or > or =5 diastolic) or the median response achieved by each drug. No difference was detected between the drugs in their effect on ambulatory BP (mean difference 1.2+/-7.1/0.7+/-5.1 mm Hg, systolic/diastolic). Significant correlations were found between the antihypertensive responses to the two drugs (r=0.77, p<0.001). Using the arbitrary response criterion, there was a difference between the drugs in the responses in 28%/13% of subjects (9/4 patients) for systolic/diastolic BP (19%/25% using the median response criterion). These data suggest that in some hypertensive patients the BP response to angiotensin-converting enzyme inhibition may fail to predict the response to ARB. It appears that there are differences in the antihypertensive action of angiotensin-converting enzyme inhibitors and ARBs that may be clinically important.