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Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share the common effect of blockade of the renin-angiotensin-aldosterone system, albeit through different mechanisms. The preponderance of consensus advice currently recommends that the primary role of ARBs in cardiovascular drug therapy be as substitute medication for patients in whom ACEIs are efficacious, but side effects like cough prove problematic. Since, despite similarities, there are distinct pharmacodynamic effects of these 2 classes of agents, Stergiou and colleagues sought to discern whether responsiveness to ACEIs was predictive of responsiveness to ARBs.
Hypertensive patients (n = 33) were randomized to receive lisinopril (20 mg QD) or losartan (50 mg QD) for 5 weeks, and then crossed over. Blood pressure was monitored by 24-hour ambulatory monitoring. "Responders" were defined as having at least a 10/5 decline in BP.
More than one-third of subjects had "discordant" responses to the 2 drugs; ie, over 33% of persons who were responders to ACEIs did not respond to ARBs, and vice versa. Stergiou et al conclude that despite their mechanistic similarities, there is diversity of responsiveness to these 2 classes of agents. Clinicians might anticipate that failure to respond to one class of agent, then, need not preclude efficacy of the other within the same patient, nor does efficacy of one class ensure efficacy of the other, within the same patient.
Stergiou GS, et al. Am J Hypertens. 2001;14:688-693.
There have been disturbances in calcium metabolism noted in hypertensive populations, including hypercalciuria associated with increased salt intake. Hypertensive animals have lower trabecular bone mineralization than normotensive controls. To investigate the association of hypertension (HTN) with bone mineral density (BMD) in humans, Tsuda and colleagues performed DEXA scans on Japanese women (n = 31) with untreated essential HTN.
Despite the fact that serum calcium, magnesium, ionized calcium, and vitamin D levels did not differ between hypertensive and normotensive women, there was a significant decrease in BMD in hypertensive women when compared with normotensives. Some of this difference was explained by a slight mean age difference in the 2 groups (hypertensive group mean age = 62, normotensive = 57). Additionally, BMD was inversely associated with systolic blood pressure. The mechanism for decreased BMD in hypertensive women is not fully understood, but in this population, hypertensive women exhibited greater urinary calcium excretion.
Tsuda K, et al. Am J Hypertens. 2001; 13:704-707.
Even after appropriate treatment for Lyme disease, some patients have persistent symptoms such as fatigue, joint and muscle pain, neurologic symptoms, and cognitive disturbance. Some anecdotal reports have indicated that prolonged antibiotic treatment courses may cause such Lyme-related symptoms to remit. To examine the role of antibiotic treatment in persons who manifest protracted symptoms associated with Lyme disease, Klempner and colleagues report on 2 randomized trials comprising seropositive and seronegative Lyme disease patients with symptoms persisting at least 6 months after acute infection (combined n = 129).
Antibiotic treatment consisted of ceftriaxone IV 2 g/d ´ 30 days followed by doxycycline 200 mg PO QD ´ 60, or placebo. Outcomes included physical and mental health scores on the SF = 36 General Health Survey.
Though the original intention of Klempner et al had been to enroll 260 patients, the data as analyzed by the safety monitoring board suggested that the study be discontinued early, since no demonstrable improvement was discernible in patients receiving active antibiotic treatment, and continuing the study longer was highly unlikely to indicate a favorable response.
Klempner MS, et al. N Engl J Med. 2001;345:85-92.