In a double-blind randomised parallel group trial comprising 146 patients, a new calcium antagonist, isradipine, was compared with hydrochlorothiazide with regard to blood pressure lowering effect and adverse events during treatment of mild to moderate hypertension. Isradipine was given in doses between 2.5 and 10mg twice daily, and hydrochlorothiazide at a dosage of 25 to 50mg once daily for 10 weeks. Both treatments reduced blood pressure, with no difference between the treatment groups, and the number of responders did not differ. Patients not obtaining a diastolic blood pressure ≼ 90mm Hg on monotherapy received the second drug, with a further relevant lowering of blood pressure. More patients experienced newly occurring adverse events during treatment with isradipine (44) than with hydrochlorothiazide (28; p < 0.05). Palpitation, flushing and oedema were all more common in the isradipine group. Mean doses during therapy were isradipine 11.7 mg/day and hydrochlorothiazide 39.8 mg/day. During treatment with isradipine, white blood cells (p < 0.01), alkaline phosphatase (p < 0.0001), albumin (p < 0.05) and serum calcium (p < 0.05) increased, whereas serum potassium (p < 0.05) decreased. Hydrochlorothiazide decreased serum sodium (p < 0.01) and serum potassium (p < 0.01), but increased serum uric acid (p < 0.001).

In a double-blind randomised group comparative trial the adverse effects of the β-blockers acebutolol and metoprolol were compared in patients with arterial hypertension. The patients were asked before and during treatment about a number of complaints/symptoms, known to be common adverse reactions to β-blockers. A total of 215 patients were randomised, and 82 in each group completed 16 weeks’ treatment. No statistically significant differences were found in the reduction in blood pressure and heart rate, and confidence limits excluded major differences. After 4 weeks the heart rate was reduced more in the metoprolol group than in the acebutolol group. Before and after 16 weeks’ treatment no differences were found in either the number of patients with complaints/symptoms or in the severity of these complaints. Both parameters were reduced evenly during the study. Patients receiving metoprolol complained more often of palpitations 4 weeks after the start of treatment. Our results indicate that the choice between acebutolol and metoprolol should not be based on therapeutic efficacy or on adverse effects.

BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. METHODS In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure. RESULTS After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group. CONCLUSIONS In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)

Despite the well-known beneficial effects of lowering high blood pressure (BP), an important contributor to overall cardiovascular risk, the control of hypertension is far from being optimal, not only in the developing world but also in developed countries (1-3). Even in randomised controlled trials, where patient's motivation and physician expertise are ensured, it has been difficult to achieve optimal BP, despite the significant difference in the observed response rates (4). Among the several factors responsible for suboptimal control rates in hypertension, patient adherence, i.e., patient compliance, and persistence to treatment play crucial roles in achieving target BP values (5,6). Not surprisingly, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) has identified poor medication-taking behavior (specifically, adherence) as one of the main causes of failure to control BP in patients with hypertension (7). It is not only enough that patients take their medications regularly, but also continue to do so in the long-term in chronic diseases, such as hypertension, to avoid cardiovascular morbidity and mortality.

Background: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). Methods: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. Results: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. Conclusion: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

In a double-blind randomised parallel group trial a new angiotensin-converting enzyme (ACE) inhibitor, Spirapril, was compared to nitrendipine in 266 patients with hypertension (diastolic blood pressure 95 to 119mm Hg). Blood pressure was measured 24 hours after administration, and dose titration was performed every fourth week to achieve a diastolic blood pressure ⩽ 90mm Hg. After 4 weeks’ monotherapy with either nitrendipine 20mg once daily or Spirapril 12mg once daily, the dose was increased to 40mg once daily and 24mg once daily, respectively, if goal blood pressure had not been achieved. After 8 weeks of monotherapy hydrochlorothiazide 12.5mg once daily could be added.

Pinacidil is a new vasodilating agent. Previous studies have shown that the effect on blood pressure is related to the serum concentration. This study compared a sustained release tablet with a controlled release capsule formulation developed to extend the duration of the antihypertensive effect. 12 patients with severe essential hypertension requiring basic therapy with a diuretic, a β-adrenoceptor blocker and pinacidil participated in this randomised crossover study. All patients had received pinacidil at a constant dosage for more than 6 months. When the same dose was given, the capsule formulation gave a lower peak serum concentration of pinacidil and pinacidil N-oxide compared with the tablet formulation. The maximum serum concentration (Cmax) was more extended, with a Cmax/2 of 9.5 hours after the capsule compared with 6 hours after the tablet. Neither formulation lowered blood pressure in any patient for 12 hours. Thus, if blood pressure reduction is considered essential during the whole dose interval, twice-daily administration of the capsule formulation is not sufficient.