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Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension.

Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension

Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension.

Michael A. Weber, MD; Ernesto L. Schiffrin, MD; William B. White, MD; Samuel Mann, MD; Lars H. Lindholm, MD; John G. Kenerson, MD; John M. Flack, MD; Barry L. Carter, Pharm D; Barry J. Materson, MD; C. Venkata S. Ram, MD; Debbie L. Cohen, MD; Jean-Claude Cadet, MD; Roger R. Jean-Charles, MD; Sandra Taler, MD; David Kountz, MD; Raymond R. Townsend, MD; John Chalmers, MD; Agustin J. Ramirez, MD; George L. Bakris, MD; Jiguang Wang, MD; Aletta E. Schutte, MD; John D. Bisognano, MD; Rhian M. Touyz, MD; Dominic Sica, MD; Stephen B. Harrap, MD

Clinical Practice Guidelines for the Management of Hypertension in the Community

Michael A. Weber, MD; Ernesto L. Schiffrin, MD; William B. White, MD; Samuel Mann, MD; Lars H. Lindholm, MD; John G. Kenerson, MD; John M. Flack, MD; Barry L. Carter, Pharm D; Barry J. Materson, MD; C. Venkata S. Ram, MD; Debbie L. Cohen, MD; Jean-Claude Cadet, MD; Roger R. Jean-Charles, MD; Sandra Taler, MD; David Kountz, MD; Raymond R. Townsend, MD; John Chalmers, MD; Agustin J. Ramirez, MD; George L. Bakris, MD; Jiguang Wang, MD; Aletta E. Schutte, MD; John D. Bisognano, MD; Rhian M. Touyz, MD; Dominic Sica, MD; Stephen B. Harrap, MD

A comparative trial of controlled-onset, extended-release verapamil, enalapril, and losartan on blood pressure and heart rate changes.

BACKGROUND The excess morning risk of myocardial infarction and stroke may be attributable to the rapid rise in blood pressure (BP) and heart rate in the hours after awakening. The aim of this randomized, double-blinded, placebo-controlled, multicenter study was to compare once-daily, controlled-onset, extended-release (COER-24) verapamil to enalapril and losartan on BP and heart rate during the postawakening morning phase as well as throughout the 24-h period. METHODS A total of 406 patients were randomized to an 8-week forced-titration period with one of the following: 1) COER-24 verapamil 240 mg/day titrated to 360 mg/day; 2) enalapril 10 mg/day titrated to 20 mg/day, 3) losartan 50 mg/day titrated to 100 mg/day, or 4) placebo. Office BP and heart rate and ambulatory 24-h BP monitoring was performed at baseline, 4 weeks, and 8 weeks. RESULTS Each active treatment, as compared with placebo, lowered BP both during the morning hours as well as the entire 24-h period. COER-24 verapamil was more effective in lowering morning systolic (-16.6 mm Hg) and diastolic (-11.9 mm Hg) BP than either enalapril or losartan (P < .001). For the entire 24-h period, the effects of COER-24 verapamil (-11.6/-8.4 mm Hg) were comparable to enalapril (- 13.4/-8.3 mm Hg; P = NS). Losartan achieved a similar 24-h effect on systolic pressure (-9.3 mm Hg) but was less effective on diastolic pressure (-5.4 mm Hg; P = .004 v COER-verapamil). Unlike losartan or enalapril, COER-24 verapamil was the only treatment to lower the heart rate over both the 24-h period (-4.6 beats/min; P < .001) and during waking hours (-4.6 beats/min; P < .001). A blunted rate of rise in BP, heart rate, and rate-pressure product occurred during the postawakening period with COER-verapamil (P = .03) but not with either of the other treatment arms. Lastly, the decline in BP at night was similar for COER-verapamil and losartan and greater with enalapril (P = .014) CONCLUSIONS COER-24 verapamil produces changes in BP and pulse that more closely match the normal circadian hemodynamic rhythms than either do enalapril or losartan.

Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril

Drug therapy often fails to control hypertension. Azilsartan medoxomil (AZL-M) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability. This double-blind, controlled, randomised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with clinic systolic blood pressure (SBP) 150–180 mm Hg. Patients were randomised (n=884) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks, then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks. The primary endpoint was change in trough, seated, clinic SBP. Mean patient age was 57±11 years, 52.4% were male, 99.5% were Caucasian. Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg. Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM (P<0.001 for both AZL-M doses). Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg (2.4% and 3.1%, respectively) than with RAM (4.8%). These data demonstrated that treatment of stage 1–2 hypertension with AZL-M was more effective than RAM and better tolerated.

Comparison Of Antihypertensive Efficacy Of The New Angiotensin Receptor Blocker Azilsartan Medoxomil With Ramipril: Pp.16.112

Objective: We compared the blood pressure (BP)–lowering efficacy and safety of the new angiotensin II receptor blocker (ARB) azilsartan medoxomil (AZL-M), with the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with stages 1–2 systolic hypertension. Design and Method: In this 24-week, double-blind study, patients with a clinic systolic BP (SBP) of 150–180 mm Hg were randomly assigned to receive AZL-M 40 or 80 mg QD or RAM 10 mg QD; subjects received low doses (AZL-M 20 mg or RAM 2.5 mg) for the initial 2 weeks. The primary endpoint was change in trough sitting clinic SBP; secondary endpoints were changes in clinic diastolic BP, 24-hour ambulatory BP parameters, response rates (clinic BP less than 140/90 mm Hg and/or reduction of 20/10 mm Hg or more from baseline), and safety parameters. Results: A total of 884 subjects (mean age 57 ± 11 years, 47.6% female) underwent randomization (5 were not treated). Baseline BPs were similar in each group (Table). AZL-M 40 and 80 mg reduced clinic and 24-hour mean SBP significantly more than RAM. Response rates were higher with AZL-M 40 and 80 mg than RAM (54.0%, 53.6%, and 33.8%, respectively; P < 0.001). Adverse events leading to discontinuation (2.4%, 3.1%, and 4.8%) and cough (1.0%, 1.4%, and 8.2%) were less frequent with AZL-M 40 and 80 mg than with RAM, respectively. Conclusions: Long-term treatment with AZL-M was more effective at reducing BP compared to RAM 10 mg, and AZL-M was well tolerated in patients with stage 1–2 hypertension. Figure 1. No caption available.

Potassium homeostasis in health and disease: A scientific workshop cosponsored by the National Kidney Foundation and the American Society of Hypertension

While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for recommending potassium intake and often limits the use of renin-angiotensin-aldosterone system blockers in patients with heart failure and chronic kidney diseases. New agents for managing hyperkalemia may alter the long-term management of heart failure and the hypertension, proteinuria, and further function loss in chronic kidney diseases. In this jointly sponsored effort between the American Society of Hypertension and the National Kidney Foundation, 3 panels of researchers and practitioners from various disciplines discussed and summarized current understanding of the role of potassium in health and disease, focusing on cardiovascular, nutritional, and kidney considerations associated with both hypo- and hyperkalemia.

Pharmacokinetics and pharmacodynamics of torasemide in patients with chronic renal insufficiency—Preliminary evaluation

SummaryThe pharmacokinetics and pharmacodynamics of torasemide were studied in 24 subjects with chronic renal insufficiency. The subjects were divided into two groups of patients, half having a creatinine clearance <30 ml/min and the other half having a creatinine clearance between 30 and 60 ml/min. Three different intravenous doses were studied in each patient group. Pharmacokinetic analysis revealed dose proportionality when relating area under the concentration curve to dose. There was a progressive decrease in renal clearance of torasemide with declining renal function. In contrast, there was no difference in serum elimination half-life among the patients. In addition, this half-life was not different from that observed in healthy young or elderly control subjects. In previous reports on patients with congestive heart failure and liver disease, serum half-life values were prolonged compared to that of control subjects, presumably due to decreased hepatic, nonrenal clearance of torasemide. Supportive of this hypothesis is the considerably increased area under the serum vs. concentration time curve in such patients. In summary, this study has shown that the serum half-life of torasemide would be unchanged in patients with renal disease. The ceiling dose for torasemide (i.e., the dose above which no further drug-induced natriuresis is obtained) has been preliminarily found to be a single 100-mg intravenous dose in patients with moderate renal insufficiency and a single 200-mg intravenous dose in patients with severe disease.

Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension Weber et al.

Michael A. Weber, MD; Ernesto L. Schiffrin, MD; William B. White, MD; Samuel Mann, MD; Lars H. Lindholm, MD; John G. Kenerson, MD; John M. Flack, MD; Barry L. Carter, Pharm D; Barry J. Materson, MD; C. Venkata S. Ram, MD; Debbie L. Cohen, MD; Jean-Claude Cadet, MD; Roger R. Jean-Charles, MD; Sandra Taler, MD; David Kountz, MD; Raymond R. Townsend, MD; John Chalmers, MD; Agustin J. Ramirez, MD; George L. Bakris, MD; Jiguang Wang, MD; Aletta E. Schutte, MD; John D. Bisognano, MD; Rhian M. Touyz, MD; Dominic Sica, MD; Stephen B. Harrap, MD

RESULTS OF A NOVEL ANGIOTENSIN RECEPTOR BLOCKER, AZILSARTAN MEDOXOMIL, IN PATIENTS WITH PRIMARY HYPERTENSION: 9A.01

Objective: We compared blood pressure (BP) lowering of a novel angiotensin II receptor blocker (ARB), azilsartan medoxomil (AZL-M), with placebo and another ARB, olmesartan medoxomil (OLM-M), in patients with primary hypertension using ambulatory BP monitoring (ABPM) and clinic measurement. Design and Method: In this 6-week, multicenter, double-blind, randomized controlled study, the primary endpoint was change in 24-hour mean systolic BP (SBP) by ABPM. Other outcomes were clinic BP, trough SBP at 22–24 hours by ABPM, and safety. We treated 1272 patients. Sample size was calculated for 90% power to detect a 5.5-mm Hg difference from placebo and 4 mm Hg between treatments. Results: Final ABPM data were available for 86% of patients (age 58 ± 11 yrs [mean ± SD]; 73% Caucasian, 11% African-American, 12% Hispanic; body mass index 30.2 ± 6 kg/m2). AZL-M 80 mg reduced 24-hour mean SBP most, followed by AZL-M 40 mg and OLM-M 40 mg (Table). AZL-M 80 mg lowered clinic BP more than OLM-M 40 mg (placebo-corrected difference -15.5/-8.6 vs -12.8/-7.1 mm Hg); treatment differences were -2.7 mm Hg SBP (95% CI -5.34, -0.09; P = 0.043) and -1.5 mm Hg DBP (95% CI -2.98, -0.04; P = 0.044). AZL-M tended to reduce 22- to 24-hour SBP by ABPM more than OLM-M (treatment difference -2.3 mm Hg; 95% CI -4.70, 0.04; P = 0.054). Adverse effects were similar. Headache was most common with placebo. Conclusions: AZL-M lowered 24-hour mean SBP in a dose-related fashion, and AZL-M at its maximum 80-mg dose was more efficacious than OLM-M 40 mg. Similar results for AZL-M were observed for clinic BP measurements. Figure 1. No caption available.