Efficacy and safety of ticagrelor: a reversible P2Y12 receptor antagonist.

OBJECTIVE: To summarize the pharmacokinetic and pharmacodynamic properties of ticagrelor, a selective P2Y12 receptor antagonist, and evaluate its role in the treatment of patients with acute coronary syndromes (ACS). DATA SOURCES: A literature search was conducted in MEDLINE (1966-November 2009), International Pharmaceutical Abstracts (1970-November 2009), and EMBASE (1990-November 2009) using the MeSH terms and key words AZD6140, ticagrelor, P2Y12 receptor antagonist, cardiovascular disease, ACS, atherothrombosis, and platelets. STUDY SELECTION AND DATA EXTRACTION: Selected studies evaluated the pharmacology, pharmacokinetics, pharmacodynamics, safety, and efficacy of ticagrelor for the treatment of ACS. DATA SYNTHESIS: Ticagrelor selectively and reversibly blocks the P2Y12 receptor, inhibiting platelet aggregation and preventing amplification of platelet activation. Optimal dosing strategy as determined by ticagrelor's pharmacokinetic and pharmacodynamic profile is a loading dose of 180 mg followed by 90 mg by mouth twice daily. At these doses, greater platelet inhibition is observed with ticagrelor as compared to clopidogrel 75 mg once daily in both clopidogrel-experienced and -naïve patients. Studies in patients experiencing ACS concluded that ticagrelor reduced the rate of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and overall mortality compared to clopidogrel without increasing major bleeding when administered with standard therapy for ACS. There was no significant difference in the risk of stroke with ticagrelor compared to clopidogrel; however, intracranial bleeding was more common with ticagrelor. Ticagrelor is well tolerated; however, minor bleeding, dyspnea, hypotension, nausea, and ventricular pauses were reported more frequently than with clopidogrel. Reversible inhibition with ticagrelor may allow for more rapid surgical intervention after discontinuation, suggesting greater flexibility in treatment of ACS. CONCLUSIONS: Ticagrelor's improved pharmacokinetic and pharmacodynamic profile builds upon the limitations of currently available P2Y12 receptor antagonists. Ticagrelor represents a promising approach for the prevention of cardiovascular events in patients with ACS.

Managing peripheral edema in patients with arterial hypertension.

Calcium channel blockers (CCBs) play a vital role in the management of hypertension. Peripheral edema is the most common side effect reported with CCB monotherapy, especially with high-dose dihydropyridine CCBs. CCB-related peripheral edema is a dose-limiting effect that is usually medically benign but can compromise patient adherence. CCB-related peripheral edema may cause considerable discomfort and patient concern. Patients presenting with peripheral edema should undergo assessment for drug and nondrug causes. Rather than lowering the CCB dose or switching to another monotherapy, combination therapy (e.g, CCB plus a renin-angiotensin-aldosterone system inhibitor) can enhance blood pressure control, generally with lower doses of individual agents, and lessen the risk of adverse events. As recommended by consensus guidelines, addition of a renin-angiotensin-aldosterone system inhibitor as part of combination therapy may accelerate the time to goal blood pressure as well as help alleviate peripheral edema in affected patients. Successful management of CCB-related peripheral edema with lifestyle changes and rational combination therapy is likely to improve blood pressure control and patient outcomes.

Optimizing management of hypertension with combination therapy: considerations for the nurse practitioner.

Hypertension is an important contributor to the risk of cardiovascular disease and death, yet success in achieving blood pressure (BP) control has been limited. Most patients will require 2 or more medications to control their BP. Nurse practitioners play a vital role in treating patients with hypertension and can help overcome barriers to reaching BP goals. Measures to improve therapeutic adherence include educating the patient and simplifying the medication regimen. Use of single-pill combination therapy, which reduces the pill burden, can contribute to improved medication persistence and compliance. Rational combination therapy combines medications with complementary mechanisms of action, such as a calcium channel blocker (CCB) and a renin-angiotensin-aldosterone system (RAAS) inhibitor; it is often more efficacious than monotherapy and allows the use of lower doses of the individual components, which usually results in improved tolerability. Current guidelines support the first-line use of combination therapy in many patients. Initiating therapy with a RAAS inhibitor-based combination can reduce BP and cardiovascular risk and may be more effective for some patients than traditional combinations such as a beta-blocker with a diuretic. Adverse events associated with any medication can compromise its therapeutic usefulness. Peripheral edema is a common and dose-dependent adverse event seen with dihydropyridine CCBs, which can cause marked patient distress, reduce adherence to therapy, and result in dose reduction or even discontinuation of therapy. In most cases, CCB-induced peripheral edema can be managed successfully, and CCB therapy need not be abandoned. Management strategies include nonpharmacologic and pharmacologic measures. Several clinical trials have shown a lower incidence of peripheral edema in patients receiving combination therapy with a CCB and a RAAS blocker compared with CCB monotherapy.

Efficacy and safety of darusentan: a novel endothelin receptor antagonist.

OBJECTIVE: To summarize the role of the endothelin system (ETS) in cardiovascular disease (CVD) and evaluate the potential usefulness of darusentan, a selective endothelin type A (ET(A)) receptor antagonist, in the treatment of hypertension and chronic heart failure (CHF). DATA SOURCES: A literature search was conducted in MEDLINE (1966-February 2008), International Pharmaceutical Abstracts (1970-February 2008), and EMBASE (1990-February 2008) using the search terms endothelin, darusentan, LU 135252, hypertension, and heart failure. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the role of the ETS in CVD and the pharmacology, pharmacokinetics, safety, and efficacy of darusentan for the treatment of hypertension and CHF were included. DATA SYNTHESIS: Darusentan represents a novel treatment strategy for patients with resistant hypertension. Its safety and efficacy have been evaluated in the treatment of hypertension and CHF. Darusentan selectively blocks the ET(A) receptor, promoting vasodilatation and preventing several proliferative and inflammatory processes, while promoting the actions of the ET(B) receptor. Studies in patients with stage 2 or resistant hypertension concluded that darusentan safely and effectively lowers blood pressure. Darusentan's unique mechanism of action, dose-dependent blood pressure-lowering profile, once-daily dosing regimen, and sustained 24-hour blood pressure-lowering effect are valuable features. Darusentan is well tolerated, with only peripheral edema, headache, and nasal symptoms being reported more frequently than with placebo. Endothelin receptor antagonists, including darusentan, have been associated with a decrease in hemoglobin and hematocrit and are teratogens. Darusentan does not appear to cause hepatotoxicity. Additional studies in CHF are warranted to assess the safety and efficacy of darusentan, especially given its association with peripheral edema and decreased red blood cell count. CONCLUSIONS: Given the important role of the ETS in hypertension and available data with darusentan, selective antagonism of the ET(A) receptor represents a promising approach to managing resistant hypertension. Darusentan's role will be more clearly elucidated by ongoing Phase 3 studies.

Dihydropyridine calcium channel antagonists in the management of hypertension.

Dihydropyridine calcium channel antagonists have been maligned in recent years because of concerns regarding their cardiovascular and overall safety profile. Specifically, it was widely publicised in the mid-1990s that these agents might increase the risk of myocardial infarction, gastrointestinal bleeding and cancer. Data linking these agents with increased cardiovascular risk were based on nonrandomised studies and implicated short-acting, immediate-release agents. These results were inappropriately extrapolated to longer-acting compounds, extended-release products, and to the non-dihydropyridine class. Fortunately, recent studies have vindicated the class from safety allegations. These studies are reviewed herein. Compared with both diuretics and contemporary agents, amlodipine decreases cardiovascular events to a similar or greater extent without evidence for increased coronary heart disease, gastrointestinal bleeding or cancer. Despite these data, initial concerns have had lasting repercussions, as the use of dihydropyridine calcium channel antagonists appears to lag behind what emerging data would support. Dihydropyridine calcium channel antagonists have several noteworthy attributes that merit consideration in the management of hypertension. The blood pressure response to this class of drugs is less contingent on patient factors such as age and race compared with other antihypertensive agents (e.g. ACE inhibitors). Dihydropyridine calcium channel antagonists may exert effects that protect against stroke that are independent of their blood pressure-lowering mechanism. Unlike diuretics and beta-adrenoceptor anatagonists (beta-blockers), dihydropyridine calcium channel antagonists are lipid neutral and do not disturb glucose homeostasis. Dihydropyridine calcium channel antagonists demonstrate a highly desirable profile when administered as part of combination therapy. Combinations of dihydropyridine calcium channel antagonists and ACE inhibitors or angiotensin receptor antagonists display additive efficacy and an enviable adverse-effect profile. Collectively, the cardiovascular benefit, metabolic neutrality and homogeneous blood pressure response illuminated in recent studies, and reviewed here, represent a reaffirmation of the benefit of long-acting dihydropyridine calcium channel antagonists and should serve to help reinforce the critical importance of these agents in the therapeutic armamentarium against cardiovascular disease.

Drug evaluation: PSN-9301, a short-acting inhibitor of dipeptidyl peptidase IV.

(OSI) Prosidion is developing PSN-9301, a rationally designed dipeptidyl peptidase IV inhibitor acquired from Probiodrug AG, as a potential oral treatment for type 2 diabetes. Phase II clinical trials of PSN-9301 are underway.

Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff.

The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, beta-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of beta-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by beta-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient.

Optimal pharmacological therapy for community-acquired pneumonia: the role of dual antibacterial therapy.

The optimal pharmacological therapy of community-acquired pneumonia (CAP) is one of the most ardently debated issues in medicine. Presently, most guidelines recommend either a fluoroquinolone alone or dual therapy with a third-generation cephalosporin plus a macrolide in patients hospitalised with CAP, but few provide clinicians with specific considerations for selecting from these agents. Despite a similar spectrum of activity and favourable resistance patterns (for fluoroquinolones and third-generation cephalosporins) against CAP pathogens, there is emerging evidence that dual therapy may be superior to monotherapy in certain populations.In patients with non-severe CAP, the evidence supports the use of either monotherapy or dual therapy in most patients; however, patients with severe CAP or bacteraemic pneumococcal CAP experience improved survival when treated with dual therapy. It is unclear from this evidence if any specific combination of agents is the most effective, but the combination of a third-generation cephalosporin plus a macrolide is the most extensively studied. Dual therapy was superior to monotherapy irrespective of the susceptibility of the aetiological pathogen, thus insufficient antimicrobial spectrum does not explain the disparity. The most likely explanation for improved outcomes with dual therapy is the combined effect of optimised antimicrobial spectrum (including atypicals), decreased impact of resistance to a single agent and the immunomodulatory effects of macrolides. Increasing resistance in patients with non-severe CAP warrants the consideration of dual therapy and perhaps a reappraisal of agents usually reserved for second-line therapy, including doxycycline, in these populations as well. In light of the available evidence, dual therapy should be strongly considered in all patients with severe CAP, especially when complicated by pneumococcal bacteraemia.

Can the renin-angiotensin system protect against stroke? A focus on angiotensin II receptor blockers.

From a patient's perspective, stroke is the most devastating form of cardiovascular disease, representing the number one cause of permanent disability in the United States. Treatment of hypertension significantly reduces the risk of stroke; however, it is unclear whether all antihypertensive agents are equivalent in this regard. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the risk of cardiovascular events, including stroke. Although attenuation of the renin-angiotensin system (RAS) is often credited with the blood pressure-independent effects of this class of agents, this hypothesis has not been confirmed with regard to the end point of stroke. In fact, drugs that activate the RAS, such as diuretics and dihydropyridine calcium channel blockers, are as effective or superior to ACE inhibitors for stroke prevention. Angiotensin II receptor blockers (ARBs) selectively block the angiotensin II subtype I receptor, which results in a reflexive increase in levels of angiotensin II and unopposed activation of angiotensin II subtype 2 receptors. Clinical trials comparing ARBs with active controls have reported significant reductions in stroke in ARB-treated patients. Data on ARBs and other drugs that activate the RAS (diuretics and dihydropyridine calcium channel blockers) support a potential role for the RAS in protecting against stroke. Ongoing trials with ARBs are evaluating stroke as a primary end point, and results should help to further elucidate the role of ARBs in this disease. Until then, it is prudent to treat hypertension with an agent or combination of agents that are likely to result in a rapid and sustained reduction in blood pressure, taking into consideration patient characteristics, comorbidities, tolerability, and cost.

Elevations in serum creatinine concentration: concerning or reassuring?

The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has significantly reduced morbidity and mortality across the continuum of vascular disease. The utilization of these agents, however, remains suboptimal. The drugs are not prescribed in many patients because of concerns regarding their effects on renal function. Despite overwhelming evidence in favor of renoprotection, it is not uncommon for the glomerular filtration rate (GFR) to decrease shortly after starting treatment with an ACE inhibitor or ARB. This response is functional in nature and should be expected based on renal physiology and its dependence on the renin-angiotensin system to maintain GFR. Unfortunately, this phenomenon sometimes is viewed as an adverse effect or an indicator of underlying pathology. Although somewhat counterintuitive, early elevations in serum creatinine concentration are associated with improved long-term renal outcomes in patients with renal insufficiency and thus support, rather than condemn, continued treatment. Clinicians should be aware of the physiologic course associated with blockade of the renin-angiotensin system so that these agents will not be withheld unnecessarily.

Management of hypertension with fixed-dose triple-combination treatments.

The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed that half the patients with hypertension have uncontrolled blood pressure (BP), with underlying factors including therapeutic inertia and poor patient adherence. Many patients will require three antihypertensive agents to achieve BP goals, and current guidelines recommend combining drugs with complementary mechanisms of action. Three single-pill triple-combination treatments are available and each includes an agent affecting the renin-angiotensin-aldosterone pathway (either a direct renin inhibitor or an angiotensin II receptor blocker) in combination with a calcium channel blocker and diuretic. These triple-combination therapies consistently demonstrated significantly greater BP reduction relative to the component dual combinations, with BP reductions documented across a range of patient populations. Triple-combination treatments were well tolerated in all clinical trials reviewed. The use of single-pill, triple-combination antihypertensive therapy has been shown to be an effective, well-tolerated, and convenient treatment strategy that can help patients achieve BP control.

SGLT-2 inhibitors and their potential in the treatment of diabetes.

Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors improve glucose control to an extent comparable to other hypoglycemic agents while simultaneously reducing body weight, blood pressure, and cholesterol - an admirable portfolio. One agent, canagliflozin, has recently been approved by the US Food and Drug Administration (FDA) and two other agents have progressed through Phase III trials, including dapagliflozin and empagliflozin. Collectively, when used as monotherapy, these agents have demonstrated reductions in hemoglobin A1c (HbA1c), body weight, and blood pressure of -0.34% to -1.03%, -2.0 to -3.4 kg, and -1.7 to -6.4 mmHg/-0.3 to -2.6 mmHg (systolic blood pressure/diastolic blood pressure), respectively. SGLT-2 inhibitors have been well tolerated, with hypoglycemia (0.9% to 4.3%) occurring infrequently in clinical trials. Safety signals related to breast and bladder cancer have arisen with dapagliflozin, though these are unsubstantiated and likely ascribed to the presence of preexisting cancer. As these agents emerge, clinicians should embrace the addition to the formulary for treating type 2 diabetes, but must also weight the risk-benefit of this new class in deciding which patient types are most likely to benefit from their novel mechanism of action.

The evolving landscape of RAAS inhibition: from ACE inhibitors to ARBs, to DRIs and beyond.

Chronic renin-angiotensin-aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to cardiovascular (CV) disease and renal dysfunction. The vascular effects of sustained RAAS activation are associated with hemodynamic imbalances, as well as inflammatory stimulation and prothrombotic processes that lead to fibrosis, endothelial dysfunction and cellular remodeling. RAAS inhibition therapies, which include the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and more recently, direct renin inhibitors, have been used in clinical practice for more than 30 years. Our understanding of how these drugs work, alone and in combination, has contributed to an expanding landscape of treatment options and established RAAS inhibition as essential for reducing the risk of CV and renal disease. This perspective provides a historical overview of how RAAS inhibitors have evolved to their present-day status and will discuss recently discovered functions for components of this complicated and powerful regulatory system.

Dapagliflozin: a novel sodium-glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.

The prevalence of diabetes mellitus has grown to staggering numbers, and its incidence is expected to rise in the next 2 decades. The need for novel approaches to treat hyperglycemia cannot be ignored. Current agents have been shown to modestly improve glycemia and in some cases prevent complications of diabetes, but they become less effective over time and are often accompanied by undesirable adverse effects. Dapagliflozin is the lead agent in a new class of oral antidiabetic agents known as sodium-glucose cotransporter type 2 (SGLT2) inhibitors, which represent a novel approach to the management of type 2 diabetes mellitus. By selectively and reversibly blocking the SGLT2 receptor, dapagliflozin prevents the reabsorption of glucose at the renal proximal tubule. Phase II and III clinical trials have demonstrated that dapagliflozin is a safe and effective method for treating type 2 diabetes. Dapagliflozin produces a sustained, dose-dependent reduction in plasma glucose levels while simultaneously improving insulin secretion and sensitivity. Over 12-24 weeks, reductions in hemoglobin A(1c) ranged from 0.54-0.89% when dapagliflozin was administered once/day (either as monotherapy or add-on therapy to oral antidiabetic drugs with or without insulin) to patients with type 2 diabetes. Therapy with dapagliflozin also results in a mild osmotic-diuretic effect that may account for decreases in total body weight (~2-3 kg) and blood pressure (systolic 2-5 mm Hg, diastolic 1.5-3 mm Hg), and increases in hematocrit (1-2%). Dapagliflozin has a favorable safety profile, with the rates of hypoglycemia similar to those of placebo. Genital and urinary tract infections were more commonly reported in patients taking dapagliflozin (2-13%) than those taking placebo (0-8%). Dapagliflozin does not appear to cause electrolyte disturbances, hepatotoxicity, or nephrotoxicity. Results from clinical trials have been promising, and well-designed clinical programs that address the long-term safety and efficacy of dapagliflozin are under way.

Carvedilol reduces aortic wave reflection and improves left ventricular/vascular coupling: a comparison with atenolol (CENTRAL Study).

Blood pressure (BP) characteristics, such as central aortic pressure and arterial stiffness, independently predict cardiovascular events. The effects of pharmacologically dissimilar ß-blockers on these properties have not been fully elucidated. Patients with essential hypertension and without significant concomitant cardiovascular disease were randomly assigned to controlled-release carvedilol, force-titrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg (n=19); each was given once daily for 4 weeks. Baseline characteristics were similar. At the end of week 4, atenolol and carvedilol reduced central and brachial systolic and diastolic BP to a similar extent. Central augmentation index was increased in atenolol-treated patients but not carvedilol-treated patients (atenolol 4.47% vs carvedilol -0.68%; P=.04). Mean augmented central aortic pressure increased slightly during atenolol treatment (+1.1 mm Hg) but decreased slightly during carvedilol treatment (-1.1 mm Hg), although the difference in these changes was not statistically significant (P=.23). Pulse pressure amplification was reduced more with atenolol at week 4 (atenolol -10.7% vs carvedilol -1.8%; P=.02). Therefore, we conclude that carvedilol results in more favorable pulse pressure amplification and augmentation index by increasing arterial compliance and reducing the magnitude of wave reflection, respectively, compared with atenolol.

Aliskiren and valsartan combination therapy for the management of hypertension.

Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA), a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI) to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.

Improving blood pressure control rates by optimizing combination antihypertensive therapy.

IMPORTANCE OF THE FIELD: Hypertension is the most common preventable cause of cardiovascular morbidity and mortality. Despite the availability of a multitude of antihypertensive drugs, blood pressure (BP) control rates remain poor in the majority of patients with hypertension due to both patient- and clinician-related factors. The purpose of this review is to describe how healthcare professionals can best utilize combination therapy to optimize patient antihypertensive treatment and achieve BP goals. AREAS COVERED IN THIS REVIEW: Data are discussed describing the common need for multiple antihypertensive agents for achieving BP control, importance of the time required for BP control on patient outcomes, and key clinical trial experiences for guiding decisions in antihypertensive regimen selection, with particular attention to the efficacy and tolerability of triple-therapy combinations and the benefits and disadvantages of single-pill formulations for combination regimens. Literature searches of these various topics were conducted in July 2009 (using no time period limits), with the paper later updated with published literature available as of May 2010 (including abstracts from the 2010 annual meeting of the American Society of Hypertension). WHAT THE READER WILL GAIN: The reader will derive an appreciation for general need for the use of two, and often three or more, antihypertensive agents for achieving BP goals, supporting the importance of thorough patient assessment in determining the appropriateness of combination therapy early in the course of treatment. They will also be updated as to the clinical trial data available for triple-therapy combinations, including both published and recently presented data. TAKE HOME MESSAGE: By optimizing efficacy, decreasing side effects, and increasing adherence, combination therapy using single-pill combinations can improve outcomes in patients with mild to moderate hypertension.

Nonpharmacological interventions for the treatment of rheumatoid arthritis: a focus on mind-body medicine.

Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects approximately 1.3 million Americans. It is characterized by inflammation of the joints, most often affecting the hands, hips, and knees. Presently, there is no cure, and the commonly used pharmacological therapies are not always effective and have significant side effects, especially when used long term. Consequently, there is a need for alternative treatments for RA. Mind-body medicine (MBM), which uses the mind to affect disease processes, is a promising area for many pathological conditions, especially autoimmune disorders like RA. In this review, we highlight the basis for psychological-based interventions for the treatment of RA. The notion that the mind has an impact on immune function and several processes that underpin the pathophysiology of RA is well established. Correspondingly, there are several lines of evidence to indicate that psychological-based interventions can favorably affect these processes. Clinical trials of MBM in RA have most commonly assessed outcomes such as pain, functional disability, psychological status, coping abilities, self-efficacy, and joint involvement. Across studies, statistically significant improvements were found for all outcomes, though the clinical significance of these changes is open to interpretation. Given that the RA patients included in these studies had generally maximized the use of pharmacological options, any additional therapeutic benefit may be considered significant. Patients with a history of depression appear to exhibit heightened responsiveness to MBM, and this is a group that should be preferentially targeted. Based on the current evidence, MBM can be recommended as an adjunct to conventional therapy to enhance treatment response and possibly reduce the use of more risky pharmacological therapies.