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Keywords: treatment indication, cut-off points, stratification, albumin excretion rate, microalbuminuria, Type 2 diabetes, irbesartan Abstract Hypothesis The efficacy of a treatment in a clinical trial depends in part on where the cut-off point is placed for the test result used to select patients for the trial, and this applies to irbesartan in the Irbesartan Microalbuminuria II (IRMA II) trial for preventing nephropathy. Patients and methods Patients in the IRMA II trial were stratified into different pre-treatment albumin excretion rate (AER) ranges to compare the proportion of patients starting in these different ranges (i) that progressed to develop nephropathy within 24 months and (ii) whose AER was over 40 µg/minute at three months. Results The proportion of patients with pre-treatment AER values between 20 and 40 µg/minute progressing to develop nephropathy was 1.25% in the placebo group and 0.78% in the irbesartan group, while for pre-treatment AER values between 41 and 200 µg/minute, 24.4% and 11.2% develop nephropathy respectively in the placebo and irbesartan groups. In patients with a pre-treatment AER of 20 to 30 µg/minute, 32.5% and 13.6% respectively in the placebo and irbesartan groups had a value exceeding 40 µg/minute at three months. Conclusions The data demonstrate that irbesartan is effective in reducing the onset of nephropathy within two years when the pre-treatment AER is above 40 µg/minute, but if the AER is below this level it progresses unusually to nephropathy within two years. Irbesartan also slows progression of AER to over 40 µg/minute for patients with pre-treatment AER values at or above 20 µg/minute and these patients should be treated.

Objective To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the β-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment Methods A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP ≥ 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. Results Similar significant reductions in SiSBPs (mean ± SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 ± 10.3 and 173.5 ± 10.7 mmHg at baseline to 149.0 ± 15.5 and 148.2 ± 15.3 mmHg after 16 weeks of losartan or atenolol treatment, respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P= 0.029). Conclusion It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.

A 38-year-old woman with systemic lupus erythematosus (SLE) and an acute neurological event was studied with computed tomography (CT) and magnetic resonance (MR). Marked intracranial calcification mimicking that seen in hypoparathyroid states was found. The clinical significance of this finding is not clear and the mechanism for cerebral calcification remains unknown.