Clinical Briefs: ARBs and Headache; Lower Doses of HRT; Pulse Pressure and Cardiovascular Disease Mortality
By Louis Kuritzky, MD
Efficacy of Angiotensin II Receptor Antagonists in Preventing Headache
Headache is among the most commonly reported events in placebo-controlled trials of pharmaceutical agents, usually occurring in both the recipients of active drug and placebo. It has not gone unnoticed that, in contrast to some other antihypertensive agents which have been associated with increases in headache, angiotensin II receptor antagonists (ARBs) have often demonstrated reduced headache incidence when compared to placebo.
To clarify whether this favorable effect of ARB upon headache was consistent, Etminan and colleagues analyzed 27 studies, including more than 12,000 patients, who had received ARB treatment in placebo-controlled trials. In addition, trial data had to include headache either as a primary outcome or as one of the listed adverse effects.
Overall, the risk of headache in recipients of ARBs was reduced about one third compared to placebo. This compares favorably with the headache reduction seen in migraine prophylaxis trials using ACE inhibitors (22% reduction).
Although headache was not further delineated in this report by subtype (eg, migraine, tension, cluster), this report suggests that there has been good consistency between studies. To date, there has not been a comparison trial between ACE inhibitors and ARBs.
Etminan M, et al. Am J Med. 2002; 112:642-646.
Effect of Lower Doses of HRT on Bone in Early Postmenopausal Women
In addition to relief of vasomo- tor symptoms, postmenopausal hormone replacement therapy (HRT) has been shown to improve bone mineral density (BMD). Traditionally, 0.625 mg of conjugated equine estrogen (CEE) daily, or the equivalent, has been viewed as "standard" dosing. Nonetheless, substantially lower doses (eg, 0.3 mg/d CEE) have been shown to provide relief for vasomotor symptoms, as well as enhance BMD when combined with calcium supplementation. Combined HRT (estrogen + progestogen) studies have suggested that CEE + medroxyprogesterone acetate (MPA), is either neutral, or possibly beneficial for BMD.
In this report, Lindsay and colleagues examined the effects of various doses of CEE (0.3-0.625 mg/d) and MPA (1.5-2.5 mg/d) in healthy postmenopausal women. End points included BMD (spine and hip) and markers of bone turnover (eg, osteocalcin, urinary telopeptides).
All treatments were superior to placebo for BMD in spine and hip, as well as markers of bone turnover. Standard’ dose CEE (0.625 mg/d) alone was superior to CEE 0.3mg/d alone. The addition of MPA had no effect, positive or negative, on BMD except in women using higher dose CEE (0.625 mg/d), in whom the effect was favorable. Lindsay et al conclude that lower dose CEE-MPA does reduce bone loss in postmenopausal women.
Lindsay R, et al. JAMA. 2002;287: 2668-2676.
Pulse Pressure and Cardiovascular Disease-Related Mortality
The population of men screened for participation in the Multiple Risk Factor Intervention Trial (MRFIT) has provided a large population (n = 342,815) from which to derive important observational epidemiologic data. Men were screened from 1973 until 1975, and followed for cardiovascular mortality until 1996.
Pulse pressure ( = SBP-DBP) has been increasingly recognized as a predictive factor for cardiovascular morbidity and mortality. Pulse pressure rises as large artery elasticity is lost. Hence, an increased pulse pressure reflects increasing arterial rigidity.
In the MRFIT screenees, the SBP and DBP showed a stronger association with cardiovascular mortality than pulse pressure. Using any 2 of the 3 variables (DBP, SBP, pulse pressure) was superior to any one individual variable for predicting adverse cardiovascular outcome. Intuitively, it can be recognized that at lower levels of blood pressure (eg, 120/50), the pulse pressure alone (= 70), even though the same as that seen at 160/90 (= 70) would not likely reflect cardiovascular risk. However, in support of the predictive role of pulse pressure, in this population the men suffering elevated SBP with the LOWEST DBP (thus, with the highest pulse pressure), experienced the highest cardiovascular mortality rates.
Domanski M, et al. JAMA. 2002;287:2677-2683.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.
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