Robert Guthrie

An acculturation scale for Southeast Asians.

SummaryThis article reports the development of an acculturation scale for Southeast Asian immigrants. From factor analyses of responses on 13 items obtained from samples of three different Southeast Asian ethnic groups, i.e., Cambodians, Laotians, and Vietnamese, two subscales were derived: (1) proficiency in languages (land of origin versus English), and (2) language, social and food (LSF) preferences. Inter-item reliability of the scales was demonstrated for each of the three ethnic groups, with Cronbach alpha coefficients of 0.76 or above. Construct validity was also established within each of the three ethnic groups by demonstrating expected associations of the subscales with current age, years in the USA, total years of education, percentage of lifetime in the USA, and age on entering the USA. Multivariate analyses within each of the ethnic groups revealed that, once controlling for years of education, percentage of lifetime in the USA, and type of health care coverage, although not significant for the Cambodians (P=0.08) males tended to show higher scores for the proficiency in language subscale in comparison to females. Similar multivariate analyses for the LSF preference subscale showed that although slightly higher for the males, the differences between the genders was not significant for the Cambodians (P=0.78); both the Laotian (P=0.23) and Vietnamese (P=0.01) females showed higher scores in comparison to males although only just reaching significance for the Vietnamese.

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.

Dose-Related Antihypertensive Effects of Irbesartan in Patients With Mild-to-Moderate Hypertension

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

An elective-titration study of the comparative effectiveness of two angiotensin II-receptor blockers, irbesartan and losartan

This multicenter, randomized, double-masked, elective-titration study was designed to compare the effectiveness, safety, and tolerability of irbesartan and losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of patients with mild-to-moderate hypertension. After a 3-week, single-masked, placebo lead-in period, 432 patients with a mean seated diastolic blood pressure (SeDBP) of 95 to 115 mm Hg were randomly allocated to receive either irbesartan 150 mg once daily (n = 213) or losartan 50 mg once daily (n = 219). At week 4, if SeDBP at trough (i.e., 24 +/- 3 hours after the previous dose) was > or = 90 mm Hg, the daily dose was doubled (to irbesartan 300 mg or losartan 100 mg). At week 8, if trough SeDBP was > or = 90 mm Hg, hydrochlorothiazide 12.5 mg once daily was added to the regimen; consistent with the prescribing information for losartan, the dose of losartan was reduced to 50 mg once daily on the addition of hydrochlorothiazide. A total of 370 patients (178 irbesartan and 192 losartan) were evaluable for efficacy. The mean change in trough SeDBP at week 8, the primary efficacy end point, was significantly greater in patients receiving irbesartan monotherapy than in those receiving losartan monotherapy (-10.2 mm Hg vs -7.9 mm Hg, respectively). At week 12, reductions in trough SeDBP and seated systolic blood pressure were greater with irbesartan treatment than with losartan treatment (-13.8 mm Hg vs -10.8 mm Hg and -18.0 mm Hg vs -13.9 mm Hg, respectively), and a greater proportion of irbesartan patients responded to therapy (i.e., trough SeDBP < 90 mm Hg or reduction in trough SeDBP > or = 10 mm Hg) compared with losartan patients (78% vs 64%, respectively). Both regimens were well tolerated.

The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the First Myocardial Infarction Risk Reduction Program

BACKGROUND Noncompliance with cardiovascular therapy and prevention initiatives is well documented. OBJECTIVES The purpose of the First Myocardial Infarction (MI) Risk Reduction Program, an open-label drug registry involving mainly primary-care patients at increased risk of a first MI, was to examine the effects of postal and telephone reminders, as well as demographic and other baseline characteristics, on patient self-reported compliance with pravastatin treatment. A second objective was to determine whether regimen adherence was associated with the adoption of other lifestyle modifications recommended to decrease the risk of coronary artery disease. METHODS Patients with risk scores of > or = 4 on a scale of -1 to +16 for men and -1 to +17 for women on the First Heart Attack Risk Test were considered to be at increased risk of a first MI and eligible for enrollment in the registry program. An elevated total cholesterol level despite dietary interventions was an additional inclusion criterion. Patients were prospectively randomized (4:1) to either an intervention involving postal and telephone reminders (about coronary risk reduction and medication compliance), which were sent during the first 2 months of pravastatin treatment, or usual care. Both groups received reminder postcards at 4 and 5 months, in addition to counseling by physicians about coronary risk reduction. At 3 and 6 months (or study discontinuation), patients completed and mailed to the program-coordinating center questionnaires concerning compliance with care, including current use of prescribed pravastatin, as well as self-reported adoption of other lifestyle modifications, such as changing eating habits, losing weight, increasing physical activity, and/or quitting smoking. Compliance with pravastatin therapy and with these coronary risk-reducing behaviors was also assessed by physicians at the 3-month follow-up visit. RESULTS A total of 10,335 patients were in the intervention group, and 2765 received usual care. The 2 groups were well balanced at baseline with respect to age, race, and total cholesterol values. Neither early reminders nor baseline patient characteristics were significantly associated with reported pravastatin compliance rates, which were approximately 79% overall. However, according to self-reports at 6 months, regimen compliance was associated with the adoption of other coronary risk-reducing behaviors. CONCLUSIONS The results of this study suggest that early telephone and postal reminders do not improve compliance with drug treatment or with recommended coronary risk-reducing behaviors.

Results of Treatment With Telmisartan-Amlodipine in Hypertensive Patients

This randomized 4×4 factorial study determined the efficacy and safety of telmisartan (T) plus amlodipine (A) in hypertensive patients. Adults (N=1461) with stage 1 or 2 hypertension (baseline blood pressure [BP]: 153.2[12.1]/101.7[4.3] mm Hg) were randomized to 1 of 16 treatment groups with T 0, 20, 40, 80 mg and A 0, 2.5, 5, 10 mg for 8 weeks. In‐clinic BP reductions were greater with combination therapy than respective monotherapies. The greatest least‐square mean systolic/diastolic BP reductions were observed with T80 mg plus A10 mg (−26.4/−20.1 mm Hg; P<.05 compared with both monotherapies). BP control was also greatest in the T80‐mg plus A10‐mg group (76.5% [overall control] and 85.3% [diastolic BP control]), and BP response rates >90% with this combination. Peripheral edema was most common in the A10‐mg group (17.8%); however, this rate was notably lower when A was used in combination with T: 11.4% (T20/A10), 6.2% (T40/A10), and 11.3% (T80/A10).

The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide

The long-term safety, tolerability, and antihypertensive effects of irbesartan/hydrochlorothiazide (HCTZ) were assessed in hypertensive patients (seated diastolic blood pressure [SeDBP] 95–110 mm Hg). Patients (n = 1098) completing two randomised, double-blind trials of irbesartan alone, HCTZ alone, irbesartan/HCTZ combinations, or placebo, took 1 year of open-label therapy starting with irbesartan 75 mg/HCTZ 12.5 mg once daily. If target blood pressure (BP) (<140/<90 mm hg) was not achieved, the dose was titrated sequentially at 2- to 4-week intervals to irbesartan 150 mg/hctz 12.5 mg, then to irbesartan 300 mg/hctz 25 mg. if necessary, adjunctive therapies were added. mean changes in trough seated systolic bp/sedbp at months 2, 6, and 12 were −19.1/−14.2 mm hg (n = 941), −20.7/ −15.7 mm Hg (n = 948), and −20.6/−15.6 mm Hg (n = 898), respectively. From months 2 to 12, normalisation rates (trough SeDBP <90 mm hg) ranged from 75–85% and total responder rates (normalised or ⩾10 mm hg trough sedbp reduction) ranged from 81–91%, while target bp was achieved in 65–75% of patients. at all time-points, most patients (⩾87%) were receiving irbesartan/hctz alone. eighty-two patients (7.5%) discontinued the study due to adverse events, with half of these events considered unrelated to study medication. there were no reports of serious adverse events related to study medication. long-term therapy with irbesartan/hctz is safe, well tolerated, and maintains normalised bp in >80% of patients.

A multicenter, community-based study of doxazosin in the treatment of concomitant hypertension and symptomatic benign prostatic hyperplasia: the hypertension and BPH intervention trial (HABIT)

As men age, the incidence of both benign prostatic hyperplasia (BPH) and hypertension increases. Concomitant occurrence of these conditions also increases with age, and the 2 are frequently encountered together in primary care practice. In addition, many patients with hypertension require >1 antihypertensive agent to adequately control blood pressure. In a multicenter, community-based, 8-week, uncontrolled, open-label study, we evaluated doxazosin, a selective alpha1-adrenergic-receptor antagonist, in 491 patients with concomitant symptomatic BPH (American Urological Association [AUA] symptom score > or =12) and hypertension, some previously untreated and some with inadequately controlled hypertension (systolic blood pressure 120-179 mm Hg or diastolic blood pressure [DBP] 80-109 mm Hg) despite taking 1 or 2 antihypertensive agents. Patients were allocated to 1 of 4 groups at baseline according to their diastolic blood pressure (control was considered DBP <90 mm Hg) and whether they had received antihypertensive medication before the study. Thus the 4 groups were treated/well-controlled, treated/poorly controlled, untreated/hypertensive, and untreated/normotensive. In all patient groups, doxazosin therapy significantly improved AUA total symptom and bothersomeness scores and BPH-specific indices of health status and interference with activities (P<0.001). Significant improvements in BPH symptoms were observed with doxazosin, regardless of whether initial symptoms were moderate or severe (P<0.001). Clinically important blood pressure lowering occurred only in the patient groups in which blood pressure had been elevated at baseline. Patients whose blood pressure was poorly controlled at baseline, either without or with treatment (predominantly with angiotensin-converting enzyme inhibitors or calcium channel blockers), achieved adequate blood pressure control (reduction to <140/90 mm Hg) with the addition of doxazosin. Similar improvements in blood pressure and BPH symptoms were seen in both older (> or =65 years) and younger (45 to 64 years) patients, and doxazosin was well tolerated by both groups. The most frequent treatment-related adverse event was dizziness (13.0% of patients); however, patients classified the dizziness as mild in approximately 75% of reports, and severe dizziness was reported by only 2 patients (0.4%). Doxazosin is an effective antihypertensive agent when used in combination with agents from other antihypertensive classes in patients with poorly controlled hypertension and BPH, and is also successful as monotherapy for controlling both BPH and hypertension in patients with mild to moderate hypertension.

Efficacy and Tolerability of Irbesartan, an Angiotensin II Receptor Antagonist, in Primary Hypertension

SummaryThis study compared the efficacy and tolerability of two dose-titrated regimens of irbesartan, an angiotensin II receptor antagonist selective for the AT1 subtype, vs placebo in hypertensive patients when titrated to clinical response. Patients with seated diastolic blood pressure (SeDBP) 95 to 110mm Hg following a 4- to 5-week single-blind placebo lead-in period were randomised to double-blind irbesartan 75mg, 150mg or matching placebo administered orally once daily for 12 weeks. At week 6, the dose of double-blind medication was doubled for patients with SeDBP ≥90mm Hg. The primary outcome measure was change from baseline in SeDBP at week 12 of double-blind treatment. Mean changes from baseline in SeDBP were significantly greater for irbesartan 75mg/ 150mg (−8.3mm Hg) and 150mg/300mg (−10.5mm Hg) dose regimens vs placebo (−4.2mm Hg) [p < 0.01]. At week 12, greater proportions of patients receiving irbesartan 75mg/150mg and 150mg/300mg achieved normalised blood pressure (SeDBP <90mm Hg) vs placebo (38,53 and 24%, respectively; p < 0.01). Irbesartan was well tolerated, without evidence of dose-related adverse events.In the present study, irbesartan demonstrated dose-dependent reductions in blood pressure vs placebo. Both irbesartan regimens were equally well tolerated; however, blood pressure reduction was greater with the 150mg/300mg dose regimen. Initiation with irbesartan 150mg once daily and titrating to 300mg (if necessary) is an effective, well-tolerated, and efficient strategy for normalising blood pressure in patients with mild-to-moderate hypertension.

Review and management of side effects associated with antiplatelet therapy for prevention of recurrent cerebrovascular events

The risk of secondary events following noncardioembolic ischemic stroke or transient ischemic attack (TIA) is high and especially pronounced in the first days and weeks following the initial event; to reduce this risk, it is recommended that antiplatelet therapy be initiated immediately. Although the risk and impact of antiplatelet-associated side effects are generally far less substantial than those of secondary events, some (especially bleeding) can be severe and even life-threatening, and others may reduce adherence to antiplatelet regimens. Therefore, clinicians should implement strategies to reduce the risk of side effects and to manage those that occur. Three antiplatelet regimens have demonstrated substantial reductions in secondary event risk and are currently recommended by consensus panels: aspirin monotherapy at 50–325 mg/day; the combination of aspirin plus extended-release dipyridamole (ER-DP); and clopidogrel monotherapy. Bleeding is potentially the most significant antiplatelet-associated side effect. As bleeding risk with aspirin monotherapy is dose dependent, while preventive efficacy appears similar at all doses above 50 mg/day, aspirin doses should be kept as low as possible. Clopidogrel bleeding risk is similar to aspirin, although a reduced incidence of gastrointestinal bleeding events suggests lower gastrotoxicity. Clopidogrel should not be combined with aspirin after stroke or TIA, as the combination increases bleeding risk without improving antiplatelet efficacy. Patients should be assessed for bleeding risk (especially gastrointestinal bleeding) before initiating antiplatelet therapy; those at elevated risk should be made aware of the signs and symptoms of bleeding events to facilitate prompt treatment. The addition of ER-DP to aspirin does not increase bleeding risk, although ER-DP is associated with risk of headache, which may be severe. The prevalence of headache drops rapidly following initiation of ER-DP, suggesting most patients are able to “push through” this side effect; for those who find headache intolerable, short-term use of a reduced-dose regimen may be helpful.