The main limiting factor in patient retention was adverse drug reactions. Patients taking lamotrigine (LTG) or gabapentin (GBP) did better than those taking carbamazepine. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures.

Abstract-The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (nϭ9048) or lisinopril (nϭ9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease (ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RRϭ1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RRϭ1.07, 95% CI 0.89 to 1.28), and in women (RRϭ1.45, 95% CI 1.17 to 1.79), but not in men (RRϭ1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RRϭ1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RRϭ0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm. Key Words: antihypertensive therapy Ⅲ hypertension, detection and control Ⅲ calcium channel blockers Ⅲ angiotensin-converting enzyme Ⅲ cardiovascular diseases Ⅲ stroke Ⅲ heart failure T he success in the management of hypertension and prevention of its sequelae is owed, in part, to the many antihypertensive drugs available to physicians and patients. By the early 1990s, all of the classes of antihypertensive drugs were shown effective in lowering blood pressure (BP), but few morbidity and mortality efficacy data were available except for thiazide-type diuretics and ␤-blockers. Angiotensin-converting enzyme (ACE) inhib-

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A B S T R A C T Subsequent to studies indicating that cholecystographic agents and sulfobromophthalein (BSP) inhibit uptake of thyroxine (T4) by rat liver slices, the effect of such compounds on hepatic storage of T, in man has been examined. After intravenous administration of [1'251]T4 to five normal subjects, hepatic radioactivity, estimated by external gamma counting, rose to a peak in -4 h and then declined in parallel with serum radioactivity. When a 6-g dose of the cholecystographic agent, tyropanoate (Bilopaque), was administered orally 3 d later, estimated hepatic extravasctilar radioactivity fell 50-60% within 4 h and then rose toward the pretyropanoate value. Concomitant with the fall in hepatic radioactivity, serum radioactivity rose 57-70%, as did stable T4 levels in serum, suggesting that hormone discharged from the liver entered the serum. Both uptake ofT4 and discharge by tyropanoate were much less in two patients with liver disease.Ipodate (Oragrafin), 12 g orally in two subjects, caused much smaller changes in hepatic and serum radioactivity. However, ipodate also caused a doubling of the percenit free T4 in the serum as judged by equilibrium dlialvsis, and the ratio of hepatic radioactivity to free I' I]T4 in serum declined markedly after ipodate, similar to the fall in hepatic:serum 1251 ratios after tyropanoate. BSP, 20 mg/kg i.v. in three subjects, caused a smaller change; the decline in hepatic T4 content averaged 19%.We conclude that these organic anions, tyropanoate, ipodate, and BSP, all can displace T4 from the liver.The restults imply a link between T4 transport and organic anion transport, and indicate 'a mechanism for altering hepatic T4 content in man that could be the site of physiologic regulation or of disease. A method is described whereby analysis of the change in hepatic and plasma radioactivity after tyropanoate could be employed to estimate hepatic T4 content in diverse clinical circumstances.

Hypogeusia is a reported side effect of captopril. Linkage of hypogeusia to zinc deficiency has been suggested. We objectively assessed taste acuity using Henkin's three-drop stimulus technique and measured plasma zinc (PZn) level and urinary zinc excretion in 31 hypertensive patients. Of these, 11 were long-term, high-dose captopril recipients (more than 6 months, 266 +/- 34 mg/day), six were short-term captopril recipients (less than 6 months, 104 +/- 40 mg/daily dose), and the remaining 14 served as noncaptopril controls. Compared to controls, the long-term captopril group had significantly higher taste detection and recognition thresholds, lower PZn (91 +/- 3 vs. 100 +/- 3 micrograms/dl, P less than 0.05) and higher urinary zinc excretion (1017 +/- 89 vs. 609 +/- 76 micrograms/day, P less than 0.005). The short-term captopril group did not differ significantly from the noncaptopril group except for higher taste-recognition thresholds for NaCl and sucrose (P less than 0.05). Discontinuing captopril improved taste acuity and almost normalized zinc parameters in two patients on long-term captopril. These results suggest that abnormalities of taste are commonly associated with captopril therapy and may be related to changes in zinc metabolism. This is especially true in patients on long-term, high-dose captopril therapy.

The aim of the study was to summarize and reanalyze all available data from the literature to study the overall effect of postmenopausal hormone replacement therapy (HRT) and its various forms on hemostatic variables. Studies were identified from literature searches by Medline and Index Medicus, review articles and personal communications. Reference lists of all articles were checked to find additional studies. Principal investigators were contacted and asked to provide additional data if required. Data were collected separately for each factor of the hemostatic system. Studies written in any language were included. Each collection of studies was analyzed using standard methods for meta-analysis. A total of 76 arms of 48 studies were eligible for analysis. This included 6,119 women using HRT and 24,974 non-users. The age of investigated women was 40-68 years. HRT was associated with significantly decreased levels of fibrinogen, factor VIII, antithrombin III, and proteins C and S, but significantly increased plasminogen levels. HRT with estrogen alone or in combination with progestins, oral vs. transdermal regimens, different estrogen preparations and various progestins induced significantly different changes in many cases. In conclusion, HRT was associated with changes that could explain the increased rate of venous thrombotic events, and also with some changes that could account for beneficial vascular effects. Surprisingly, the addition of progestins induced favorable changes in many cases. Also, transdermal use was associated with more beneficial effects than oral regimens in some cases.

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