Barry L. Carter

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

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

Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order–drug–time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = −12.4±1.8 mm Hg versus −7.4±1.7 mm Hg; P=0.054; nighttime mean = −13.5±1.9 mm Hg versus −6.4±1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (−15.7±2.2 mm Hg versus −4.5±2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (−17.1±3.7 versus −10.8±3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

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

Thiazide diuretics, potassium, and the development of diabetes: a quantitative review.

National guidelines and a recent clinical trial have supported the use of thiazide diuretics as the preferred initial pharmacological treatment for hypertension. However, evidence from this and other clinical trials have also found an increased incidence of new onset diabetes among those patients receiving thiazide diuretics. The mechanisms responsible for the increased incidence of diabetes with thiazide diuretics have not been fully elucidated. This article provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance. We conducted a literature search from 1966 to June 2004 to identify clinical trials using thiazide diuretics where the metabolic effects on potassium and glucose are reported. A total of 59 clinical trials constituting 83 thiazide diuretic study arms were identified. Trial size, length, type of thiazide diuretic, and dose varied substantially among the studies. The association between average changes in potassium and glucose in the study arms is considered jointly in a weighted statistical model. The Pearson’s correlation coefficient, weighted by study sample size, for the relationship between glucose and potassium was −0.54 (95% CI, −0.67 to −0.36; P<0.01). A sensitivity analysis, which considered subset analyses and effect of covariates, as well as inverse-variance weighting, supported this finding. These data suggest that thiazide-induced hypokalemia is associated with increased blood glucose. Treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent the future development of diabetes.

Hydrochlorothiazide Versus Chlorthalidone Evidence Supporting Their Interchangeability

Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is approximately 1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.

Physician and pharmacist collaboration to improve blood pressure control.

BACKGROUND Studies have demonstrated that blood pressure (BP) control can be improved when clinical pharmacists assist with patient management. The objective of this study was to evaluate if a physician and pharmacist collaborative model in community-based medical offices could improve BP control. METHODS This was a prospective, cluster randomized, controlled clinical trial with clinics randomized to a control group (n = 3) or to an intervention group (n = 3). The study enrolled 402 patients (mean age, 58.3 years) with uncontrolled hypertension. Clinical pharmacists made drug therapy recommendations to physicians based on national guidelines. Research nurses performed BP measurements and 24-hour BP monitoring. RESULTS The mean (SD) guideline adherence scores increased from 49.4 (19.3) at baseline to 53.4 (18.1) at 6 months (8.1% increase) in the control group and from 40.4 (22.6) at baseline to 62.8 (13.5) at 6 months (55.4% increase) in the intervention group (P = .09 for adjusted between-group comparison). The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group (P < .05 for between-group systolic BP comparison). The adjusted difference in systolic BP was -12.0 (95% confidence interval [CI], -24.0 to 0.0) mm Hg, while the adjusted difference in diastolic BP was -1.8 (95% CI, -11.9 to 8.3) mm Hg. The 24-hour BP levels showed similar effect sizes. Blood pressure was controlled in 29.9% of patients in the control group and in 63.9% of patients in the intervention group (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1; P < .001). CONCLUSIONS A physician and pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates compared with a control group. Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00201019.

The Potency of Team-Based Care Interventions for Hypertension: A Meta-analysis

BACKGROUND Team-based care is the strategy that has had the greatest effect on improving blood pressure (BP). The purpose of this systematic review was to determine the potency of interventions for BP involving nurses or pharmacists. METHODS A MEDLINE search for controlled clinical trials that involved a nurse or pharmacist intervention was conducted. Mean reductions in systolic (S) and diastolic (D) BP were determined by 2 reviewers who independently abstracted data and classified the different intervention components. RESULTS Thirty-seven articles met the inclusion criteria. Education about BP medications was significantly associated with a reduction in mean BP (-8.75/-3.60 mm Hg). Other strategies that had large effect sizes on SBP include pharmacist treatment recommendations (-9.30 mm Hg), intervention by nurses (-4.80 mm Hg), and use of a treatment algorithm (-4.00 mm Hg). The odds ratios (95% confidence intervals) for controlled BP were: nurses, 1.69 (1.48-1.93); pharmacists within primary care clinics, 2.17 (1.75-2.68); and community pharmacists, 2.89 (1.83-4.55). Mean (SD) reductions in SBP were: nursing studies, 5.84 (8.05) mm Hg; pharmacists in clinics, 7.76 (7.81) mm Hg; and community pharmacists, 9.31 (5.00) mm Hg. There were no significant differences between the nursing and pharmacy studies (P > or = .19). CONCLUSIONS Team-based care was associated with improved BP control, and individual components of the intervention appeared to predict potency. Implementation of new hypertension guidelines should consider changes in health care organizational structure to include important components of team-based care.

A Cluster Randomized Trial to Evaluate Physician/Pharmacist Collaboration to Improve Blood Pressure Control

This was a prospective, cluster randomized controlled trial in patients with uncontrolled hypertension aged 21 to 85 years (mean, 61 years). Pharmacists made recommendations to physicians for patients in the intervention clinics (n=101) but not patients in the control clinics (n=78). The mean adjusted difference in systolic blood pressure (BP) between the control and intervention groups was 8.7 mm Hg (95% confidence interval [CI], 4.4–12.9), while the difference in diastolic BP was 5.4 mm Hg (CI, 2.8–8.0) at 9 months. The 24‐hour BP levels showed similar effects, with a mean systolic BP level that was 8.8 mm Hg lower (CI, 5.0–12.6) and a mean diastolic BP level that was 4.6 mm Hg (CI, 2.4–6.8) lower in the intervention group. BP was controlled in 89.1% of patients in the intervention group and 52.9% in the control group (adjusted odds ratio, 8.9; CI, 3.8–20.7; P<.001). Physician/pharmacist collaboration achieved significantly better mean BP values and overall BP control rates, primarily by intensification of medication therapy and improving patient adherence.

Evaluation of hypertensive patients after care provided by community pharmacists in a rural setting.

We evaluated blood pressure control, quality of life, quality of care, and satisfaction of patients who were monitored by specially trained community pharmacists in a group medical practice. After participating in an intensive skill development program, pharmacists performed in an interdisciplinary team in a rural clinic. The primary objective was assessed by evaluating outcome variables at 6 months compared with baseline in 25 patients randomly assigned to a study group. A control group of 26 patients was also evaluated to determine if outcome variables remained constant from baseline to 6 months. Systolic blood pressure was reduced in the study group (151 mm Hg baseline, 140 mm Hg at 6 mo, p<0.001) and diastolic blood pressure was significantly lower at 2, 4, and 5 months compared with baseline. Ratings from a blinded peer review panel indicated significant improvement in the appropriateness of the blood pressure regimen, going from 8.7 ± 4.7 to 10.9 ± 4.5 in the study group (p<0.01), but they did not change in the control group. Several quality of life scores improved significantly in the study group after 6 months (p<0.05). These included physical functioning (61.6 vs 70.7), physical role limitations (56.8 vs 72.8), and bodily pain (60.0 vs 71.7) at baseline and 6 months, respectively. There were no significant changes in the control group. Patient satisfaction scores were consistently higher in the study group at the end of the study. Our results indicate that when community pharmacists in a clinic setting are trained and included as members of the primary care team, significant improvements in blood pressure control, quality of life, and patient satisfaction can be achieved.