Treatment of Resistant and Refractory Hypertension.

Resistant hypertension (RHTN) is defined as uncontrolled blood pressure despite the use of ≥3 antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin receptor blocker), at maximal or maximally tolerated doses. Antihypertensive medication nonadherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. RHTN is a high-risk phenotype, leading to increased all-cause mortality and cardiovascular disease outcomes. Healthy lifestyle habits are associated with reduced cardiovascular risk in patients with RHTN. Aldosterone excess is common in patients with RHTN, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying RHTN, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.

Variations and practice in the care of patients with rheumatoid arthritis: quality and cost of care.

INTRODUCTION: Variability in treatment is linked to lower quality of care and higher costs. Rheumatoid arthritis (RA) is a chronic inflammatory disease for which care and management may vary considerably among rheumatologists. The extent of this variability and its cost ramifications have not been widely studied. This prospective study evaluated the quality and variability in care and quantified the potential cost implications. METHODS: We used Clinical Performance and Value® vignettes to measure the quality of RA care among community-based rheumatologists. Three online Clinical Performance and Value® vignettes--representing patients likely seen in practice with mild disease activity (case A), worsening disease activity (case B), and stable disease with a complicating comorbidity (case C)--were administered to each rheumatologist. Responses were scored against evidence-based criteria. Costs were computed using current (2011) Medicare pricing. Data were analyzed using t test and fixed-effects analysis of variance. RESULTS: One hundred eight board-certified rheumatologists (72% were male; mean age, 49.1 years) completed the study. Overall quality scores averaged 61.3%. Those employed by a health system or in a multispecialty practice were more likely to score higher. Highest combined scores for diagnosis and treatment were evident with case A (61.7%) and lowest with case C (46.7%). Up to 79% of rheumatologists ordered at least 1 laboratory test that was considered unnecessary by study protocol criteria, incurring a mean excess cost of $37.85 per physician per case. Up to 26.9% rheumatologists prescribed biologic agents that were not indicated based on American College of Rheumatology treatment guidelines, resulting in additional costs of $2041 per patient per month. CONCLUSION: In this study, we observed a wide range of reported practice variability by rheumatologists in the management of RA. This included unnecessary testing and use of biologic agents that increased the costs of treatment. Opportunities for quality improvement and cost control exist in the management of RA.

Variation in Diabetes Management: A National Assessment of Primary Care Providers.

BACKGROUND: Glucose control is monitored primarily through ordering HbA1c levels, which is problematic in patients with glycemic variability. Herein, we report on the management of these patients by board-certified primary care providers (PCPs) in the United States. METHODS: We measured provider practice in a representative sample of 156 PCPs. All providers cared for simulated patients with diabetes presenting with symptoms of glycemic variability. Provider responses were reviewed by trained clinicians against evidence-based care standards and accepted standard of care protocols. RESULTS: Care varied widely-overall quality of care averaged 51.3%±10.6%-with providers performing just over half the evidence-based practices necessary for their cases. More worryingly, provider identified the underlying etiology of the poor glycemic control only 36.3% of the time. HbA1c was routinely ordered in 91.3% of all cases but often (59.5%) inappropriately. Ordering other tests of glycemic control (done in 15% of cases) led to significant increases in identifying the etiology of the hyperglycemia. Correctly modifying their patient's treatment was more likely to occur if doctors first identified the underlying etiology (65.9% vs 49.0%, P<0.001). We conservatively estimated a US $65/patient/visit in unnecessary testing and US $389 annually in additional care costs when the etiology was missed, translating potentially into millions of dollars of wasteful spending. CONCLUSION: Despite established evidence that HbA1c misses short-term changes in diabetes, we found PCPs consistently ordered HbA1c, rarely using other available blood tests. However, if the factors leading to poor glycemic control were recognized, PCPs were more likely to correctly alter their patient's hypoglycemic therapy.

Resistant hypertension: who and how to evaluate.

PURPOSE OF REVIEW: Resistant hypertension is found in an important and rapidly growing subset of the hypertensive population, and data characterizing this group of patients are limited. The purpose of this review is to present the latest evidence on resistant hypertension, its risk factors, patient characteristics, and approach to diagnosis. We focus on important associations between resistant hypertension and primary aldosteronism and with obstructive sleep apnea. RECENT FINDINGS: Resistant hypertension comprises 20-35% of the general hypertensive population. It is important to ascertain that a patient has true resistant hypertension and not merely uncontrolled hypertension. Twenty-four-hour ambulatory blood pressure monitoring can reliably rule out a white-coat effect and may have prognostic significance in patients with resistant hypertension. Patients should be screened for secondary causes of hypertension. Primary aldosteronism is common among patients with resistant hypertension, as is obstructive sleep apnea. A plasma aldosterone to renin ratio is a useful screening tool for primary aldosteronism. Aldosterone has been found to accelerate the increase in left ventricular mass in patients with hypertension. SUMMARY: Patients with resistant hypertension comprise a unique subset, with risk factors and associations that are distinct or pronounced compared with the general hypertensive population. It is important to bear these associations in mind when dealing with patients with true resistant hypertension.

A Better Pathway? Building Consensus and Engaging Providers with Feedback to Improve and Standardize Cancer Care.

INTRODUCTION: Unwanted clinical variation is common across the United States health care system and is particularly vexing in oncology owing to the complexity, morbidity, and high cost of the disease. Efforts to standardize care including guidelines and continuing medical education have had only limited impact. Disease-specific oncology clinical pathways hold the promise of reducing variation but have been hampered by a lack of ownership and accountability among oncology providers. MATERIALS AND METHODS: We describe the utility of combining a patient simulation-based clinical variation measurement with the in-house development of multidisciplinary breast cancer pathways at a National Cancer Institute-designated cancer center. RESULTS: At baseline, we found high variation in care decisions across the multidisciplinary team and within individual specialties in the management of simulated patients. Development and introduction of breast cancer clinical pathways combined with individual and group feedback on pathway adherence led to significant increases in pathway-aligned care decisions and decreases in measured variation. Overall quality scores increased from 47.5% to 61.1% (P < .001), with the largest improvement in diagnostic accuracy (+22.1%). Providers also ordered fewer unnecessary tests, saving an estimated $305 per patient case. Adherence to preferred chemotherapy regimens increased for both medical oncologists (+16%) and other members of the multidisciplinary team (+19%). CONCLUSION: Our work shows that a structured process to measure clinical variation and provide personalized feedback to an oncology multidisciplinary team drives adoption of evidence-based pathways, less unneeded spending, and higher quality care for patients.

Drug-Drug Interaction Assessment and Identification in the Primary Care Setting.

BACKGROUND: Drug-drug interactions (DDIs) are ubiquitous, harmful and a leading cause of morbidity and mortality. With an aging population, growth in polypharmacy, widespread use of supplements, and the rising opioid abuse epidemic, primary care physicians (PCPs) are increasingly challenged with identifying and preventing DDIs. We set out to evaluate current clinical practices related to identifying and treating DDIs and to determine if opportunities to increase prevention of DDIs and their adverse events could be identified. METHODS: In a nationally representative sample of 330 board-certified family and internal medicine practitioners, we evaluated whether PCPs assessed DDIs in the care they provided for three simulated patients. The patients were taking common prescription medications (e.g. opioids and psychiatric medications) along with other common ingestants (e.g. supplements and food) and presented with symptoms of DDIs. Physicians were scored on their ability to inquire about the patient's medications, investigate possible DDIs, evaluate the patient, and provide treatment recommendations. We scored the physicians' care recommendations against evidence-based criteria, including overall care quality and treatment for DDIs. RESULTS: Average overall quality of care score was 50.5% ± 12.0%. Despite >99% self-reported use of medication reconciliation practices and tools, physicians identified DDIs in only 15.3% of patients, with 15.5% ± 20.3% of DDI-specific treatment by the physicians. CONCLUSIONS: PCPs in this study did not recognize or adequately treat DDIs. Better methods are needed to screen for DDIs in the primary care setting.

Hypertension.

Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of cardiovascular disease (CVD). Fewer than half of those with hypertension are aware of their condition, and many others are aware but not treated or inadequately treated, although successful treatment of hypertension reduces the global burden of disease and mortality. The aetiology of hypertension involves the complex interplay of environmental and pathophysiological factors that affect multiple systems, as well as genetic predisposition. The evaluation of patients with hypertension includes accurate standardized blood pressure (BP) measurement, assessment of the patients' predicted risk of atherosclerotic CVD and evidence of target-organ damage, and detection of secondary causes of hypertension and presence of comorbidities (such as CVD and kidney disease). Lifestyle changes, including dietary modifications and increased physical activity, are effective in lowering BP and preventing hypertension and its CVD sequelae. Pharmacological therapy is very effective in lowering BP and in preventing CVD outcomes in most patients; first-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium-channel blockers and thiazide diuretics.

Hyperemesis Gravidarum in Undiagnosed Gitelman's Syndrome.

Introduction. Gitelman's syndrome (GS) is an autosomal recessive inherited defect in the thiazide-sensitive sodium-chloride cotransporter (NCCT) in the renal distal convoluted tubule. Physiologic changes of pregnancy promote renal potassium wasting, but serum potassium levels are kept in the physiologic range by increased levels of progesterone, which resist kaliuresis. In the presence of GS, this compensatory mechanism is easily overwhelmed, resulting in profound hypokalemia. We present a case of an 18-year-old primigravida with undiagnosed GS who presented with hyperemesis gravidarum in her 7th week of pregnancy. This report adds to the limited experience with GS in pregnancy as reported in literature and provides additional information on medical management that leads to successful maternal and fetal outcomes.

Low Rates of Genetic Testing in Children With Developmental Delays, Intellectual Disability, and Autism Spectrum Disorders.

To explore the routine and effective use of genetic testing for patients with intellectual disability and developmental delay (ID/DD), we conducted a prospective, randomized observational study of 231 general pediatricians (40%) and specialists (60%), using simulated patients with 9 rare pediatric genetic illnesses. Participants cared for 3 randomly assigned simulated patients, and care responses were scored against explicit evidence-based criteria. Scores were calculated as a percentage of criteria completed. Care varied widely, with a median overall score of 44.7% and interquartile range of 36.6% to 53.7%. Diagnostic accuracy was low: 27.4% of physicians identified the correct primary diagnosis. Physicians ordered chromosomal microarray analysis in 55.7% of cases. Specific gene sequence testing was used in 1.4% to 30.3% of cases. This study demonstrates that genetic testing is underutilized, even for widely available tests. Further efforts to educate physicians on the clinical utility of genetic testing may improve diagnosis and care in these patients.

Antiplatelet therapy for transient ischemic attack.

Transient ischemic attack (TIA) is currently defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia without infarction. TIA is an important risk factor for stroke and other major vascular events. Risk factors for TIA or stroke need to be addressed effectively to reduce the risk for stroke in patients who have had a TIA. Aspirin (ASA) significantly reduces the risk for stroke when given after a TIA, stroke, or myocardial infarction in a dose of 50 mg/d to 325 mg/d. The role of ASA in the primary prevention of TIA or stroke, however, is less well-substantiated. Clopidogrel may be used in the secondary prevention of TIA or stroke, but its antiplatelet effect may be reduced in poor metabolizers of the drug. The combination of ASA and extended-release dipyridamole is effective in reducing risk for TIA and stroke, and may confer additional risk-lowering without an increased risk of bleeding compared with ASA alone. ASA monotherapy, clopidogrel alone, or the combination of ASA and extended-release dypiridamole are all acceptable options for initial therapy in patients with a TIA and stroke, and the combination of ASA plus extended-release dypiridamole is recommended over ASA alone.

Both morning and evening dosing of nebivolol reduces trough mean blood pressure surge in hypertensive patients.

The morning blood pressure surge (MBPS) has been shown to be an independent predictor of cardiovascular events. There is insufficient evidence on the effect of nebivolol, a vasodilating ß1-receptor blocker, on the MBPS when given in the morning or the evening. This is a prospective, randomized, double-blind, crossover study designed to test morning vs. evening dosing of nebivolol in nondiabetic, hypertensive patients. Patients received nebivolol 5 mg/day (force-titrated to 10 mg/day after 1 week) in the morning or evening and corresponding placebos. Patients underwent ambulatory BP monitoring at baseline and after each treatment phase. Forty-two patients were randomized, of whom 38 completed both study periods. Both morning and evening dosed nebivolol significantly lowered daytime, nighttime, and 24-hour BP after 3 weeks of treatment. Evening (but not morning) dosing significantly reduced prewaking systolic BP from baseline (8.64 ± 26.46 mm Hg, P = .048). Nebivolol given in the morning or the evening significantly reduces 24-hour BP parameters. Evening dosed nebivolol may confer some advantage over morning dosing in reducing prewaking systolic BP.

Refractory hypertension: definition, prevalence, and patient characteristics.

Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure.

Aldosteronism and resistant hypertension.

Resistant hypertension (RHTN) is defined as blood pressure (BP) that remains uncontrolled in spite of intake of ≥3 antihypertensive medications, ideally prescribed at optimal doses and one of which is a diuretic. The incidence of primary aldosteronism (PA) in patients with RHTN is estimated in prospective studies to be 14 to 23%, which is higher than in the general hypertensive population. Patients with PA are at an increased cardiovascular risk, as shown by higher rates of stroke, myocardial infarction, and arrhythmias compared to hypertensive individuals without PA. Likewise, RHTN is associated with adverse cardiovascular outcomes, and the contribution of PA to this increased risk is undetermined. Similar to PA, obstructive sleep apnea (OSA) is closely associated with RHTN, and a causal link between PA, OSA, and RHTN remains to be elucidated. The addition of MR antagonists to the antihypertensive regimen in patients with RHTN produces a profound BP-lowering effect, and this effect is seen in patients with or without biochemical evidence of PA, highlighting the role of relative aldosterone excess in driving treatment resistance in this group of patients.

Optimal management of hypertension in elderly patients.

Hypertension is a common and important modifiable risk factor for cardiovascular and kidney diseases. The prevalence of hypertension, particularly isolated systolic hypertension, increases with advancing age, and this is partly due to the age-related changes in the arterial tree, leading to an increase in arterial stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake, weight loss, regular aerobic activity, and moderation of alcohol consumption, have been shown to benefit elderly patients with hypertension. Lowering blood pressure (BP) using pharmacological agents reduces the risk for cardiovascular morbidity and mortality, with no difference in risk reduction in elderly patients compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in hypertensive patients regardless of age and <130/80 in patients with concomitant diabetes or kidney disease, and lowering the BP further has not been shown to confer any additional benefit. Moreover, the choice of antihypertensive does not seem to be as important as the degree of BP lowering. Special considerations in the treatment of elderly hypertensive patients include cognitive impairment, dementia, orthostatic hypotension, and polypharmacy.

Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment.

Hypertension is a very common modifiable risk factor for cardiovascular morbidity and mortality. Patients with hypertension represent a diverse group. In addition to those with primary hypertension, there are patients whose hypertension is attributable to secondary causes, those with resistant hypertension, and patients who present with a hypertensive crisis. Secondary causes of hypertension account for less than 10% of cases of elevated blood pressure (BP), and screening for these causes is warranted if clinically indicated. Patients with resistant hypertension, whose BP remains uncontrolled in spite of use of 3 or more antihypertensive agents, are at increased cardiovascular risk compared with the general hypertensive population. After potentially correctible causes of uncontrolled BP (pseudoresistance, secondary causes, and intake of interfering substances) are eliminated, patients with true resistant hypertension are managed by encouraging therapeutic lifestyle changes and optimizing the antihypertensive regimen, whereby the clinician ensures that the medications are prescribed at optimal doses using drugs with complementary mechanisms of action, while adding an appropriate diuretic if there are no contraindications. Mineralocorticoid receptor antagonists are formidable add-on agents to the antihypertensive regimen, usually as a fourth drug, and are effective in reducing BP even in patients without biochemical evidence of aldosterone excess. In the setting of a hypertensive crisis, the BP has to be reduced within hours in the case of a hypertensive emergency (elevated BP with evidence of target organ damage) using parenteral agents, and within a few days if there is hypertensive urgency, using oral antihypertensive agents.

Hypertension in the elderly.

Hypertension is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. Blood pressure elevation in the elderly is due to structural and functional changes that occur with aging. Treatment of hypertension reduces the risk of stroke, heart failure, myocardial infarction, all-cause mortality, cognitive impairment, and dementia in elderly patients with hypertension. A healthy lifestyle helps hypertension management, with benefits extending beyond lowering of blood pressure. Several classes of antihypertensive drugs are effective in preventing cardiovascular events. Treatment decisions should be guided by the presence of compelling indications such as diabetes or heart failure and by the tolerability of individual drugs or drug combinations in individual patients. The concomitant intake of certain medications that counter the effects of antihypertensive drugs and the frequent occurrence of orthostatic hypotension complicate treatment in older patients and drive down blood pressure control rates.

Reduction of blood pressure in patients with treatment-resistant hypertension.

BACKGROUND: Resistant hypertension is a common clinical problem, and patients with resistant hypertension have increased cardiovascular risk. It is a subset of the hypertensive population that is little studied and poorly characterized. OBJECTIVE: The purpose of this review is to discuss resistant hypertension, its recognition and diagnostic workup and management, and to present current data about the disease from the latest research. METHODS: We define resistant hypertension and differentiate it from pseudoresistance. We identify diagnostic tests that may be done on patients with resistant hypertension. Last, we discuss therapeutic approaches to resistant hypertension, focusing on pharmacological treatment, and present an algorithm that may be used by the clinician in treating a patient with resistant hypertension. CONCLUSION: Resistant hypertension is a significant clinical problem commonly encountered by clinicians. Patients with resistant hypertension have increased cardiovascular risk. In evaluating for resistant hypertension, it is important to recognize elements that contribute to pseudoresistance to treatment. Secondary causes of hypertension are common in patients with resistant hypertension and should be included in the diagnostic workup. Pharmacological treatment for resistant hypertension entails choosing medications with complementary mechanisms of action, optimizing diuretic use, and considering the use of mineralocorticoid antagonists as an add-on agent to the antihypertensive regimen.