Jackson T. Wright

Impact of an Electronic Medication Compliance Aid on Long-Term Blood Pressure Control

A two‐phase study was conducted to assess the effect of an electronic medication compliance aid on hypertension control and pharmaceutical compliance in ambulatory patients. In Phase I (12 weeks), 36 patients were randomly assigned to a medication vial equipped with a cap containing a digital timepiece that displays the last time the cap was removed. The control group included 34 patients randomly assigned to a standard medication vial. Subjects using the timepiece cap showed an average compliance rate of 95.1%, an average decrease in systolic pressure of 7.6 mm Hg (P = .006), and an average decrease in diastolic pressure of 8.8 mm Hg (P < .001). Controls had an average compliance rate of 78% and decreases of 2.8 mm Hg and 0.2 mm Hg in systolic and diastolic pressures, respectively. Phase 11 (12 weeks) combined use of the timepiece cap with other compliance aids: a pocket‐size card for recording blood pressure and a blood pressure cuff for self‐monitoring. Patients using the timepiece cap and the card had an average compliance rate of 98.7% with mean decreases of 11 mm Hg in systolic pressure (P < .01) and 7.64 Hg mm in diastolic pressure (P = .0001). The combined use of the cap, the card, and the blood pressure cuff resulted in an average 100.2% compliance rate with mean decreases of 15 mm Hg (P = .0006) and 6.60 mm Hg (P = .0006) in systolic and diastolic pressures, respectively. Results of the two‐phase study showed statistically significant increases in medication compliance associated with statistically and clinically significant reductions in blood pressure for all patients using the timepiece cap.

Metabolic and Clinical Outcomes in Non-Diabetic Individuals with the Metabolic Syndrome Assigned to Chlorthalidone, Amlodipine, or Lisinopril as Initial Treatment for Hypertension: A Report from the ALLHAT Study

OBJECTIVE—Optimal initial antihypertensive drug therapy in people with the metabolic syndrome is unknown. RESEARCH DESIGN AND METHODS—We conducted a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to compare metabolic, cardiovascular, and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACE inhibitor (lisinopril) in nondiabetic individuals with or without metabolic syndrome. RESULTS—In participants with metabolic syndrome, at 4 years of follow-up, the incidence of newly diagnosed diabetes (fasting glucose ≥126 mg/dl) was 17.1% for chlorthalidone, 16.0% for amlodipine (P = 0.49, chlorthalidone vs. amlodipine) and 12.6% for lisinopril (P < 0.05, lisinopril vs. chlorthalidone). For those without metabolic syndrome, the rate of newly diagnosed diabetes was 7.7% for chlorthalidone, 4.2% for amlodipine, and 4.7% for lisinopril (P < 0.05 for both comparisons). There were no differences in relative risks (RRs) for outcomes with amlodipine compared with chlorthalidone in those with metabolic syndrome; in those without metabolic syndrome, there was a higher risk for heart failure (RR 1.55 [95% CI 1.25–1.35]). In comparison with lisinopril, chlorthalidone was superior in those with metabolic syndrome with respect to heart failure (1.31 [1.04–1.64]) and combined cardiovascular disease (CVD) (1.19 [1.07–1.32]). No significant treatment group–metabolic syndrome interaction was noted. CONCLUSIONS—Despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CVD outcomes in older hypertensive adults with metabolic syndrome, as compared with treatment with CCBs and ACE inhibitors.

The effect of low-dose hydrochlorothiazide on blood pressure, serum potassium, and lipoproteins.

Recent clinical trials in hypertension suggest that thiazide diuretics may increase coronary heart deaths in selected patients, possibly through adverse effects on serum potassium, lipids, lipoproteins, and/or apolipoproteins. Administration of smaller doses of diuretics has been recommended to decrease this risk. We evaluated 12.5‐mg and 112.5‐mg daily doses of hydrochlorothiazide (HCTZ) administered for 1 month to nine postmenopausal black female hypertensives using a double‐blind, randomized, crossover design. Both regimens produced significant reductions in sitting diastolic blood pressure, a mean of 11 mm Hg with the high dose and 8 mm Hg with the low dose. The high dose produced a mean 0.7 mEq/L reduction in serum potassium while the low dose caused no change. Both doses produced similar changes in serum lipoproteins. Statistically significant elevations were seen in total cholesterol (approximately 12%), LDL cholesterol (approximately 20%), cholesterol: HDL ratio (approximately 15%), and apolipoprotein B (approximately 20%). Apolipoprotein A1 was significantly reduced (approximately 6%). These results support the use of low doses of HCTZ in mild hypertension to avoid hypokalemia, but suggest that adverse changes in serum lipids will occur.

Importance of Race/Ethnicity in Clinical Trials Lessons From the African-American Heart Failure Trial (A-HeFT), the African-American Study of Kidney Disease and Hypertension (AASK), and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Prevent Heart Attack Trial (ALLHAT) Hypertension (AASK), and the Antihypertensive and Lipid-Lowering Treatment to Heart Failure Trial (A-HeFT), the African-American Study of Kidney Disease and Importance of Race/Ethnicity in Clinical Trials : Lessons From the African-American Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright

The effect of phenylpropanolamine on ambulatory blood pressure

Phenylpropanolamine (PPA) is a sympathomimetic amine and component of many over‐the‐counter decongestants and anorectic agents. It has been reported to cause elevated blood pressure and even hypertensive crises. The pressor effects with therapeutic doses are not well established. We monitored the effects of acute and chronic PPA dosing using 24‐hour ambulatory blood pressure recording as a sensitive method of monitoring blood pressure variability. Eighteen normotensive male subjects were randomly assigned to receive 75 mg PPA (sustained‐release preparation) or placebo in a double‐blind crossover design with blood pressure monitored on days 1 (Dl) and 6 (D6) of each period. There was no significant difference in blood pressure when compared as either 2‐hour intervals or 24‐hour global means: (placebo) 116/68 (Dl), 117/68 (D6); (PPA) 118/69 (Dl), 119/69 (D6). Our results document the absence of pressor effect with PPA in therapeutic doses even with repeated measurements and further confirm the reproducibility of 24‐hour blood pressure monitoring.

Perindopril as monotherapy in hypertension: A multicenter comparison of two dosing regimens

Perindopril erbumine, a new long‐acting, non‐sulfhydryl‐containing angiotensin converting enzyme inhibitor, was evaluated in 289 patients with hypertension in a 16‐week, double‐blind, placebo‐controlled dose‐ranging study. After 4 weeks of single‐blind placebo treatment, patients with supine diastolic arterial pressures from 95 to 114 mm Hg were randomized to receive placebo, 4 mg perindopril once daily, or 2 mg perindopril twice daily. The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day. Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo (p < 0.05). The dose‐response curve flattened after 8 mg per day, and there was no difference in arterial pressure reduction or in the percentage of responders between once‐and twice‐daily administration of perindopril. Adverse reactions with perindopril were generally mild and, with the exception of cough, were similar with placebo. The findings of this study indicate that perindopril is effective, well tolerated, and suitable for once‐daily administration for the treatment of hypertension.

The effect of high‐dose short‐term ibuprofen on antihypertensive control with hydrochlorothiazide

The effect of high‐dose ibuprofen, a nonsteroidal anti‐inflammatory drug (NSAID), on the blood pressure of treated hypertensive patients was evaluated in a randomized, placebo‐controlled, double‐blind, crossover trial with 24‐hour ambulatory blood pressure monitoring. Twelve middle‐aged black women with essential hypertension, controlled with 50 mg hydrochlorothiazide per day, randomly received 3200 mg ibuprofen and a placebo for 8 days. Each treatment phase was separated by a 1‐week washout period. Ambulatory blood pressure monitoring (ABPM), body weight, and 24‐hour urinary excretion of sodium, creatinine, and prostaglandin E2 (PGE2) were determined at the end of each treatment phase. Mean (± SEM) 24‐hour systolic and diastolic blood pressures were 122/85 (±2.9/1.7) and 125/85 (±3.0/1.1) during the placebo and ibuprofen phases, respectively. Mean ABPM during six consecutive 4‐hour periods also revealed no significant differences between placebo and ibuprofen. We conclude that 3200 mg ibuprofen per day for up to 1 week induces little change in blood pressure in hypertensive patients who are receiving hydrochlorothiazide.

Profile of systemic hypertension in black patients

Hypertension extracts a huge toll from the black community in terms of excess morbidity and mortality. The black hypertensive is more likely to die from the disease and to have stroke, end-stage renal disease or heart failure. Furthermore, contrary to previous beliefs, blacks are at least as likely to have coronary artery disease as whites. Although substantial overlap occurs, the black hypertensive is more likely to be volume-expanded, to have a lower plasma renin level, and to be classified, as salt-sensitive than is the white hypertensive. Decreased dietary potassium and calcium intake, altered intra-cellular handling of sodium and calcium, and psychosocial factors have also been implicated in the pathophysiology of hypertension in blacks.

Effects of force-titrated valsartan/hydrochlorothiazide versus amlodipine/hydrochlorothiazide on ambulatory blood pressure in patients with stage 2 hypertension: the EVALUATE study.

BackgroundPrevious studies using the combination of angiotensin-receptor blockers and hydrochlorothiazide (HCTZ) have shown superior ambulatory blood pressure (ABP) reduction in study participants with stage 2 hypertension compared with monotherapy. ObjectiveThis multicenter, double-blind, parallel group, forced-titration study of individuals with stage 2 hypertension, compared the efficacy of valsartan and amlodipine in combination with HCTZ on ABP reduction. MethodsAfter a 2-week washout period, participants (n=482) with mean office sitting systolic BP ≥160u2009mmHg and ≤200u2009mmHg were randomized to receive treatment with either valsartan 160u2009mg (n=241) or amlodipine 5u2009mg (n=241), force-titrated to a maximum dose of valsartan/HCTZ 320/25u2009mg or amlodipine/HCTZ 10/25u2009mg over 6 weeks and continued through week 10. The primary endpoint was change in mean 24-h ambulatory systolic BP from baseline to week 10. ResultsAt week 10, changes from baseline in mean office BP were significantly (P<0.0001) decreased by both valsartan/HCTZ (−34.2/−14.2u2009mmHg) and amlodipine/HCTZ (−34.1/−14.7u2009mmHg). Changes from baseline in mean 24-h ABP were significantly (P<0.0001) decreased by both valsartan/HCTZ (−21.1/−12.5u2009mmHg) and amlodipine/HCTZ (−18.1/−9.9u2009mmHg). However, treatment with valsartan/HCTZ provided significant additional systolic BP (−3.8u2009mmHg; P=0.0042) and diastolic BP (−2.7u2009mmHg; P=0.0002) reduction compared with the amlodipine/HCTZ group. The proportion of individuals reaching the office goal BP (<140/80u2009mmHg) were similar in the valsartan/HCTZ (55.3%) versus amlodipine/HCTZ (54.9%) group, ABP control rates for the recommended ABP goal (<130/80u2009mmHg) were greater (P=0.0170) in the valsartan/HCTZ group (54.3%) than the amlodipine/HCTZ group (42.7%). Both treatments were well tolerated. ConclusionOn the basis of ABP monitoring but not office measurements, the fixed-dose combination of valsartan/HCTZ is a significantly more effective treatment regimen than amlodipine/HCTZ, with similar tolerability.

Ethnicity and Blood Pressure

The prevalence, impact, and control of hypertension differ across racial and ethnic subgroups in the United States population. Whether race/ethnicity should be a significant consideration in the choice of individual antihypertensive drugs continues to be a topic of intense interest and debate. This brief review will discuss recent findings that bear on the management of hypertension in these special patient groups.