Arterial Hypertension-clinical trials update 2023.

Arterial hypertension is associated with increased morbidity and mortality and research in the field is highly dynamic. This summary reviews the most important clinical trials published in 2022 and early 2023. Findings on new pharmacological approaches to treat resistant hypertension are presented and new knowledge about the optimal timing of the antihypertensive medication intake is discussed. It is focused on optimal blood pressure treatment targets and the problem of treatment and guideline inertia is acknowledged. Information about pregnancy-related hypertension is presented and blood pressure control following percutaneous thrombectomy after ischemic stroke is discussed. Finally, novel clinical data on device-based approaches to treat hypertension are summarized. The hypertension trials update summarizes the most important clincal trials on hypertension research in 2022 and early 2023. CTD - chlorthalidone, CV - cardiovascular, HCT - hydrochlorothiazide, SBP - systolic blood pressure, RDN - renal denervation *depicts systolic blood pressure only.

Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone.

BACKGROUND: Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients. METHODS: We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks. RESULTS: Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10-6 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e-7). CONCLUSION: Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.

Thiazides diuretics in the treatment of nephrolithiasis: are we using them in an evidence-based fashion?

In the 1980s a change occurred in hydrochlorothiazide prescribing practices for hypertension from high-dose (50 mg/day) to low-dose (12.5-25 mg/day) therapy. However, randomized controlled trials (RCT) for prevention of calcium-containing kidney stones (CCKS) employed only high doses (≥ 50 mg/day). We hypothesized that these practices have resulted in underdosing of hydrochlorothiazide for prevention of CCKS. Patients with a filled prescription for thiazide diuretics that underwent a 24-h urine stone risk factor analysis were eligible. Those with evidence that thiazide was prescribed for CCKS were further analyzed. Of 107 patients, 102 were treated with hydrochlorothiazide, 4 with indapamide, and one with chlorthalidone. Only 35% of hydrochlorothiazide-treated patients received 50 mg/day; a dose previously shown to reduce stone recurrence. Fifty-two percent were prescribed 25 mg and 13% 12.5 mg daily, doses that were not studied in RCT. Evidence-based hydrochlorothiazide use was suboptimal regardless of where the patient received care (Nephrology or Endocrinology clinic). In a small subset of patients (n = 6) with 24-h urinary calcium excretion measured at baseline and after 2 hydrochlorothiazide doses (25 and ≥ 50 mg), there was a trend toward decreased urinary calcium excretion as the dose was increased from 25 to ≥ 50 mg/day (p = 0.051). Low-dose hydrochlorothiazide was often used for prevention of CCKS despite the fact that there is no evidence that it is effective in this setting. This may have resulted from a practice pattern of using lower doses for hypertension therapy or a lack of knowledge of RCT results in treatment of CCKS.

Treatment of resistant hypertension.

AIM: Resistant hypertension (RH) is a common clinical problem. Patients with RH have increased cardiovascular risk. These patients also have high risk for having reversible causes of hypertension and may potentially benefit from special diagnostic or therapeutic considerations. The purpose of this review was to discuss RH, its definition, recognition, evaluation and treatment. METHODS: Authors define RH and the implications of this definition. They present latest data on its prevalence, prognostic implications, genetics, and patient characteristics. Elements of pseudoresistance and possible etiologies of treatment resistance are also identified. Lastly, diagnostic and therapeutic approaches to RH are discussed, focusing on antihypertensive medication classes that have proven benefit in patients with RH, and also on novel therapeutic approaches in these patients. CONCLUSION: RH is a common clinical problem and carries an increased risk for cardiovascular morbidity and mortality, as well as target organ damage. Patients with RH are aat high risk for reversible causes of hypertension and may benefit from special diagnostic or therapeutic considerations. Elements of pseudoresistance, intake of interfering substances and secondary causes of hypertension should be searched for and corrected, if possible. Therapeutic lifestyle modifications should be emphasized. Medical therapy includes optimizing diuretic use and considering the use of mineralocorticoid antagonists as add on antihypertensive agents. Novel approaches include surgical and transcatheter techniques, chronotherapy, and new classes of antihypertensive agents.

Antihypertensive efficacy and safety of manidipine versus amlodipine in elderly subjects with isolated systolic hypertension: MAISH study.

BACKGROUND AND OBJECTIVE: Isolated systolic hypertension (ISH) affects 10-20% of the elderly population and is strongly related to the risk of cardiovascular events. Elevated systolic BP values are primarily caused by reduced large vessel compliance with a consequent increase in total peripheral resistance. Vasodilating drugs, such as calcium channel antagonists, have proven to be effective in controlling ISH in elderly patients. This study set out to compare the antihypertensive efficacy and safety of two different calcium channel antagonists, manidipine and amlodipine, administered once daily in elderly subjects with ISH. METHODS: In a European, randomised, double-blind, multicentre, parallel-group study, after a 2-week placebo run-in period, 195 patients aged >or=60 years with ISH received manidipine 10-20 mg once daily or amlodipine 5-10 mg once daily. Chlortalidone 25mg once daily could be added to the high dose of test drug in the event of insufficient antihypertensive control. The primary efficacy parameter was the proportion of patients with a reduction in office sitting systolic BP (SBP) >or=15 mm Hg, measured at trough, at the final visit. Secondary efficacy parameters included: the proportion of patients with a normal sitting SBP value (<140 mm Hg) at the final visit; a change from baseline to the final visit in mean office trough sitting SBP; a change from baseline to the final visit in the cardiovascular risk score as measured by the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) project score; the proportion of patients with at least a two-point reduction in the cardiovascular risk score; the percentage of patients requiring upward dose titration and diuretic add-on treatment and the investigator's final judgement. Safety and tolerability evaluations were based on adverse events, ECG and laboratory tests, and clinically relevant reports of abnormalities. RESULTS: In the intention-to-treat population (n = 189), 76% and 72% of patients in the manidipine and amlodipine groups, respectively, had a reduction in sitting SBP of >or=15 mm Hg (p-value not significant for between-group comparison). The percentage of patients with a normal sitting SBP value was 52% in the manidipine group and 51% in the amlodipine group (p-value not significant for between-group comparison). Sitting SBP reductions at the end of treatment were -19.5 +/- 11.8 mm Hg in patients receiving manidipine and -18.4 +/- 11.1 mm Hg in patients receiving amlodipine. Both treatments induced a small reduction in cardiovascular risk score, with 45% of patients in both treatment groups having a two-point reduction in the final score. At the final visit, approximately half of the patients in both treatment groups were still being treated with the low dose of one of the test drugs (manidipine 10mg or amlodipine 5mg). Chlortalidone was added to the high dose of test drugs in 7% and 11% of patients in the amlodipine and manidipine groups, respectively. Both drugs were well tolerated, with a higher incidence of oedema in the amlodipine group (9% vs 4%). No clinically relevant changes in heart rate were induced by either treatment. CONCLUSION: In elderly patients with ISH, treatment with manidipine for 12 weeks was well tolerated and effective and the antihypertensive effects obtained with manidipine were the same as those obtained with amlodipine.

Foot volume increase on nifedipine is not prevented by pretreatment with diuretics.

OBJECTIVE: Despite their natriuretic effects, dihydropyridine calcium-channel blockers (CCBs) often induce ankle oedema, probably due to vasodilation in the dependent legs. Since concomitant administration of frusemide does not prevent the acute increase in foot volume on nifedipine, we investigated whether diuretic pretreatment attenuates foot swelling on CCBs. METHODS: In four separate experiments, 10 healthy volunteers received: (i) 20 mg of nifedipine without active pretreatment (pretreatment with placebo only); (ii) 20 mg of nifedipine after 5 days' treatment with amiloride 5 mg twice daily; (iii) 20 mg of nifedipine after 5 days' treatment with chlorthalidone 50 mg once daily; and (iv) no active drugs (pretreatment with placebo and placebo in place of nifedipine) as the control. Foot volumes were measured using an accurate water displacement technique (intra-individual coefficient of variance 0.27%). RESULTS: Amiloride and chlorthalidone pretreatment induced marked volume depletion, with a 2-3% reduction in body weight, a 5-10% increase in haematocrit and a 14-23% increase in plasma colloid osmotic pressure. In addition, the mean +/- SEM foot volume after both chlorthalidone (1282 +/- 37 ml) and amiloride (1289 +/- 40 ml) was lower than without pretreatment (1315 +/- 38 ml) (P < 0.05). Neither amiloride nor chlorthalidone significantly influenced the acute increase in foot volume on nifedipine. However, due to pretreatment effects, the foot volume after nifedipine was higher (P < 0.05) without pretreatment (1356 +/- 36 ml) than after amiloride (1318 +/- 38 ml) or chlorthalidone (1319 +/- 37 ml). Amiloride significantly attenuated the natriuretic effect of nifedipine, whereas chlorthalidone prevented the nifedipine-induced rise in colloid osmotic pressure and haematocrit. CONCLUSIONS: Diuretic pretreatment and the concomitant volume depletion did not prevent acute foot swelling on nifedipine, although the absolute foot volume remained lower after such pretreatment. Therefore diuretics mitigate the oedema of CCBs, but do not directly interfere with oedema formation.

Patterns of potassium wasting in response to stepwise combinations of diuretics in nephrotic syndrome.

OBJECTIVE: To study the urinary potassium wasting patterns when the decreasing effectiveness of diuretics during repeated administrations are counterbalanced by stepwise increases of doses and combinations of them. PATIENTS: Eleven patients with renal edema. Seven patients suffered from advanced nephrotic syndrome and 4 patients were "forme fruste". METHODS: Urinary excretions and serum levels of potassium, sodium, creatinine, osmoles were determined; specific renal functions, glomerular filtration rate (GFR) fractional excretion of potassium (FE(K)), transtubular potassium gradient (TTKG) and free water reabsorption (TcH2O) were calculated. Nine different intervention-induced changes were followed daily: furosemide (FSD) alone, FSD with chlorthalidone (CTN), "low dose" and "high dose" potassium sparing drugs (PSD), FSD with CTN and "low dose" or "high dose" PSD, and "no drug" as well as "postdiuretic" periods with or without PSD. RESULTS: TTKG significantly decreased in response to FSD. It elevated during FSD with CTN, but remained lower than the baseline. The normal correlation between urinary potassium excretion (UKV) and TTKG became distorted under FSD. UKV and FE(K) were slightly increased by FSD and more markedly when given FSD together with CTN, probably because "distal volume flow" was elevated. In the "postdiuretic" periods TTKG increased, but this was reversed by PSD. In response to PSD, TTKG and UKV decreased, but both were elevated when combining with FSD + CTN. CONCLUSIONS: FSD caused relatively small potassium loss, because the enhanced "distal volume flow" was counterbalanced by a decrease of TTKG. FSD may have had a potassium secretion inhibitory influence as well. Potassium loss and TTKG were enhanced during coadministration of CTN, and decreased by PSD. "Postdiuretic rebound" increase of TTKG was reversed by PSD.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Antihypertensive efficacy and tolerability of different drug regimens in isolated systolic hypertension in the elderly.

The pharmacological treatment, mainly based on diuretics, of isolated systolic hypertension (ISH) has recently been shown to reduce the risk of stroke and coronary heart disease in the elderly. The purpose of this study was to compare the antihypertensive effect and tolerability of different drug regimens in elderly subjects with ISH (systolic blood pressure--SBP-- > or = 160 mmHg and diastolic blood pressure--DBP-- < 90 mmHg). A multicentre, randomized, controlled open trial was planned in the general practice setting. Four widely used treatment schedules were tested: hydrochlorothiazide 25 mg plus amiloride 2.5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol 50 mg (At) and atenolol 25 mg plus chlorthalidone 6.25 mg (At+C). After a baseline evaluation, 308 patients (76.3% female, mean age 75.3 +/- 7.1 years) were randomized and followed up for 6 months. After 3 months the drug dosage was doubled if the systolic blood pressure goal (SBP < 160 mmHg and SBP reduction of at least 20 mmHg) had not been reached. Ninety-four subjects (30.5%) presented contraindications to beta-blockers. At the 3rd- and 6th-month visits all treatment groups, except At, showed a significant reduction in SBP compared to the control group; DBP showed no significant reduction in any group at any time. At the end of the follow-up the percentage of hypertensives who had reached the BP goal was 14.6% in the control group, 52.9% in H+Am, 54.8% in N, 28.6% in At and 52.2% in At+C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of a combination of a diuretic and nifedipine retard for the treatment of hypertensive patients refractory to nifedipine retard]. / Evaluación de la asociación de un diurético a nifedipina retard como terapia en pacientes hipertensos refractarios a nifedipina retard.

This study assessed the effectivity of the association between a diuretic, chlorthalidone, and retard nifedipine in the treatment of patients above 50 years of age with Arterial Hypertension refractory to retard nifedipine. A prospective study of a 3-month controlled intervention was designed, in which the patients were treated with retard nifedipine for 2 months and, if they did not respond to the treatment, chlorthalidone was associated for 1 month. Out of 235 patients selected at the beginning of the study, 28 dropped out voluntarily, 24 were excluded because they did not adhere to the protocol and 30 dropped out due to side effects. After the first two months of therapy, hypertension was controlled in 60.2% of the 181 patients, whereas in the third month, only in 20% of the 44 patients considered could be controlled. Significant differences were observed between the two treatments (p < 0.001) with a 95% CI in the percentage differences of 54% versus 26.4%. These results suggest that the association of chlorthalidone and retard nifedipine does not improve the treatment of Arterial Hypertension refractory to retard nifedipine.

Abnormal electrocardiograms and cardiovascular risk: role of silent myocardial ischemia. Evidence from MRFIT.

The Multiple Risk Factor Intervention Trial (MRFIT) was designed as a primary prevention study to test the effect of multifactorial intervention on long-term outcome in men with a combination of risk factors that placed them in the top 10-15 percentiles of risk for coronary artery disease. Of the 12,866 patients in this study, the 3,600 men (about 28%) with abnormalities in the baseline electrocardiogram were prospectively identified. They were expected to be at increased risk for coronary events compared with those without electrocardiographic abnormalities. Analysis of cumulative mortality data following antihypertensive regimens that included high dosages of diuretics revealed an association between electrocardiographic abnormalities at rest and diuretic treatment that related to adverse outcome. When the dosages of the diuretic were lowered, this trend was reversed. It is proposed that diuretic-related hypokalemia may predispose patients who may have silent myocardial ischemia to potentially fatal arrhythmias and that use of potassium-sparing antihypertensive regimens be considered in high-risk hypertensive patients.

Angiotensin converting enzymes from urine of treated and untreated essential mild hypertensive patients (EHP) with diuretic: partial purification and characterization.

Urine of untreated EHP was eluted, on a ion-exchange chromatography, in two protein peaks with ACE activity, at 0.7 mS (BI) and 1.25 mS (BII), while urine of treated EHP, was eluted only in one peak with ACE activity (0.7 mS). BI (Mr, 88 kDa) and BII (Mr, 61 kDa) convert AI to AII, hydrolyze bradikinin, are inhibited by captopril, EDTA and metal ions.

Effects of nifedipine-GITS on left ventricular mass and left ventricular filling.

Sixteen patients with initial diastolic blood pressure greater than or equal to 120 mm Hg were treated for 1 year with extended-release nifedipine [nifedipine-GITS (gastrointestinal therapeutic system)]. Serial changes in left ventricular mass index and associated alterations in left ventricular systolic function, left ventricular filling, plasma renin activity, atrial natriuretic peptide, and catecholamines were evaluated. Blood pressure was significantly reduced from 200 +/- 8/122 +/- 3 mm Hg (mean +/- SEM) to 144 +/- 5/89 +/- 2 mm Hg (p less than 0.0001) at 1 year. Eleven patients (69%) required only nifedipine-GITS for blood pressure control and 5 (31%) required the addition of chlorthalidone. After 6 months, the left ventricular mass index was significantly reduced by 19% from 121 +/- 8 to 96 +/- 7 g/m2 and this reduction was sustained at 1 year. Septal and posterior wall thicknesses were reduced from 13.4 +/- 0.1 to 11.2 +/- 0.04 mm and from 12.8 +/- 0.1 to 10.0 +/- 0.03 mm (p less than 0.001), respectively. Prevalence of left ventricular hypertrophy decreased from 63 to 25%. Left ventricular fractional shortening increased from 34 to 42% (p less than 0.05) and the relationship between fractional shortening and end-systolic stress did not change. Over the year of sustained blood pressure reduction, the peak velocity of early filling increased from 58 to 63 cm/s (p = 0.07), the peak velocity of late filling did not change, and the ratio of late to early peak velocity of left ventricular filling significantly decreased (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of left ventricular mass and associated changes in neurohormones and atrial natriuretic peptide after 1 year of sustained nifedipine therapy for severe hypertension.

Sixteen patients with severe hypertension were treated for 1 year with extended release nifedipine, during which time serial changes in left ventricular mass index and associated alterations in left ventricular systolic function, left ventricular filling, plasma renin activity, atrial natriuretic peptide and catecholamines were evaluated. Mean seated blood pressure (+/- SE) was significantly reduced from 200 +/- 8/122 +/- 3 to 144 +/- 5/89 +/- 2 mm Hg (p less than 0.0001) at 1 year. After 6 months, left ventricular mass index was significantly reduced by 19% from 121 +/- 8 to 96 +/- 7 g/m2 and this reduction was sustained at 1 year. Septal and posterior wall thickness were reduced from 13.4 +/- 0.1 to 11.2 +/- 0.04 mm and from 12.8 +/- 0.1 to 10.0 +/- 0.03 mm (p less than 0.001), respectively. The prevalence of left ventricular hypertrophy decreased from 63% to 25%. Left ventricular fractional shortening increased from 34 +/- 2% to 41 +/- 3% (p less than 0.05) and the relation between fractional shortening and end-systolic stress did not change. Over the year of sustained blood pressure reduction, the peak velocity of early filling increased from 57 +/- 3 to 63 +/- 4 cm/s (p = 0.07), peak velocity of late filling did not change and the ratio of late to early peak left ventricular filling velocity significantly decreased (p less than 0.05). Plasma atrial natriuretic peptide levels, markedly elevated at entry, decreased from 70 +/- 15 to 41 +/- 8 pg/ml at 1 year (p less than 0.05). Plasma renin activity and catecholamine levels were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

[Electrocardiographic and echocardiographic changes during antihypertensive therapy]. / Modificazioni elettrocardiografiche ed ecocardiografiche durante terapia antipertensiva.

To investigate the changes of electrocardiographic and echocardiographic indexes of left ventricular hypertrophy (LVH) during antihypertensive therapy, 100 hypertensive patients, mean age 46 years, were studied in pretreatment condition and during 12 months of antihypertensive therapy. In pretreatment condition, 83 patients showed LVH by echocardiography (echo; left ventricular mass index greater than 130 g/m2) and 30 patients had LVH by electrocardiography (ECG) (Sokolow index greater than 35 mm). In comparison to echo index of LVH, Sokolow index showed a sensibility of 34% and a specificity of 88%. Both LV mass echo index and ECG index significantly decreased after 3 months but in different way. LV mass index mainly decreased after 12 months, whereas Sokolow index particularly decreased after 6 months, with no further changes in the subsequent months. After 12 months of therapy, the LV mass echo index normalized in 19% of the patients (16/83) and Sokolow index normalized in 57% (17/30). ECG sensibility and specificity, in comparison to LV mass echo, was 20% and 100%, respectively. Thus, ECG appears less sensitive than echo in the detection of LVH. During antihypertensive therapy ECG index of LVH normalized more precociously and to a greater extent than the echo index. However, the normalization of LVH by ECG does not necessarily mean that a complete anatomic regression of LVH has occurred.

[A multicenter study comparing nitrendipine and chlorthalidone in elderly hypertensive patients]. / Estudio multicéntrico comparativo entre nitrendipino y clortalidona en pacientes ancianos hipertensos.

One hundred and eleven low-moderate hypertense elderly patients treated with nitrenpidine or chlortalidone were studied during 4 months either on monotherapy or in combination according to the therapeutic response observed. The therapeutic goal (diastolic arterial pressure less than 95 mmHg) was obtained in 92.4% of patients on nintrenpidine and in 49.1% on chlortidone, both on monotherapy (2 months) (p less than 0.001). At the end of the study 96.3% of patients reaches the therapeutic goal. Secondary effects were observed in 8.3% of patients on nitrenpidine and 6.1% on chlortalidone and in 11.1% of patients on combined treatment. No abnormalities were observed in blood biochemistry studied nor was there evidence of a significant influence of any of the two drugs on the patients quality of life which was evaluated through a specific questionnaire specially designed.

[Comparison of chlorthalidone and sustained-action nifedipine in the treatment of mild to moderate arterial hypertension]. / Comparación de la clortalidona y nifedipina retardada en el tratamiento de la hipertensión arterial leve-moderada.

The effectiveness and safety of sustained action nifedipine (NF) were compared to those of chlorthalidone (CL) in two groups of 35 and 37 patients with mild to moderate hypertension followed up for 4 months. There was a significant reduction in blood pressure (BP) after 15 days of therapy. The degree of control was acceptable with both drugs. A second drug was required in 20% patients of the NF group and in 30.8% of CL group. The therapeutic goal (BP less than 160/95) was achieved in 86.7% of patients in CL group and in 48.4% of those in NF group. We found 48.8% of dropouts in the NF group and none in CL group. There was a significant increase in blood glucose in CL group and a reduction of uric acid and an increase of HDL-cholesterol in NF group. Both drugs are useful to treat hypertension, although NF has the drawback of a high dropout rate and CL induces abnormalities in biochemical parameters.

Haemodynamic resistance of forearm vessels during prolonged drug treatment of essential hypertension.

In 40 patients with essential hypertension, the authors studied the haemodynamic resistance in forearm vessels before and after 15-min arterial occlusion, and changes in this parameter during a three-year combined antihypertensive treatment. The study revealed that the 15-min occlusion did not entirely suppress the contractile activity of vascular smooth muscles. Under these conditions, the minimum vascular resistance reflects the sum of structural and functional alterations. The character of change in minimal haemodynamic vascular resistance depends on the mechanism of action of the antihypertensive drugs. Administration of the post-synaptic alpha-adrenergic blocker Pratsiol produces a decrease in the minimal haemodynamic vascular resistance.

Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study.

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 randomly 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 randomly 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.