When One Antihypertensive Med is Not Enough: Which Combination?
Source: Kato J, et al. J Am Soc Hypertens 2012;6:393-398.
The ALLHAT trial is the largest hypertension clinical trial ever done, originally enrolling more than 42,000 individuals. That trial concluded that a thiazide diuretic (chlorthalidone) was at least as good as — and in some situations superior to — a calcium channel blocker ([CCB] amlodipine) or an angiotensin converting enzyme inhibitor ([ACE] lisinopril), and that an alpha blocker (doxazosin) was inferior to any of the three others.
But ALLHAT also demonstrated that only about 25% of hypertensives are able to maintain control on one medication. So, when one antihypertensive med is not enough, which combination should we choose?
The ACCOMPLISH trial was the first to address this question on a large-scale basis (n = 11,506) by directly comparing ACE/CCB (benazepril/amlodipine) with ACE/diuretic (benazepril/hydrochlorothiazide). In this trial, outcomes were superior for ACE/CCB.
Not everyone can tolerate an ACE, most commonly due to cough. Kato et al performed a clinical trial to compare in 58 hypertensive elderly patients (mean age, 72 years) the efficacy of an angiotensin receptor blocker (ARB)/CCB (mostly olmesartan/amlodipine) with ARB/diuretic (mostly olmesartan/indapamide).
At the conclusion of the trial, the ARB/CCB combination provided superior blood pressure reduction to ARB/diuretic. The diuretic used in ALLHAT was chlorthalidone, which is definitely more potent than hydrochlorothiazide; whether substitution of chlorthalidone for indapamide in this trial might have tipped the scales in another direction remains unknown.
Vitamin D for Osteoarthritis: NOT
Source: McAlindon T, et al. JAMA 2013; 309:155-162.
For a burgeoning population of baby-boomers who wish to continue being physically active despite advanced years, tools to provide symptomatic relief from osteoarthritis (OA) are valuable (e.g., topical and systemic NSAIDs, opioids, physical therapy), but disease-modification is really the "holy grail." At the current time, we do not possess any disease-modifying pharmacotherapy for OA.
Since vitamin D (VID) is an important player in bone health, might it influence symptoms or disease progression of OA? McAlindon et al performed a 2-year randomized, placebo-controlled trial of VID in subjects with symptomatic OA of the knee. VID dose was titrated from 2000 IU/d up to as much as 8000 IU/d, depending on attainment of a goal plasma VID level between 36-100 ng/mL. In this population of mostly Caucasian adults (mean age, 62 years) living in the Boston area, it is perhaps not surprising that baseline levels of VID averaged 22 ng/mL.
At the end of the trial, no effect (positive or negative) was seen from supplementation with VID on either OA symptoms or evidence of disease progression as measured by degree of cartilage loss.
Early Identification of COPD Exacerbations
Source: Yanez AM, et al. Chest 2012; 142:1524-1529.
Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are consequential: 10% of patients admitted to the hospital die, 25% of those admitted to the ICU die, and the mortality rate in the year following an AE-COPD hospitalization for those who are discharged home is as high as 43%. Even after successful recovery from an AE-COPD, decrements in pulmonary function from pre-event status are noted that are not regained. Early identification of AE-COPD, with an intent-to-treat with minimum delay, might possibly alter the ominous natural history of AE-COPD.
Historically, it has been shown that the increasing dyspnea characteristic of AE-COPD typically begins about 5 days before patients seek consultation from their clinician. For asthma, wider swings in variation between morning and evening peak flow rate herald an acute deterioration, even before patients are overtly symptomatic. In a similar vein of thought, the authors postulated that changes in respiratory rate would signal an impending AE-COPD.
Oxygen-dependent COPD patients (n = 89) were asked to monitor respiratory rate daily for 3 months. Monitoring of daily respiratory rate (DRR) was performed automatically by installing a monitoring device to the patients' oxygen delivery systems. Although respiratory rate was monitored at three different times each day, only the mean DRR rate was used for evaluation.
During 3 months of follow-up, 30 of the 89 patients required hospitalization for AE-COPD. Baseline average DRR for the group as a whole was 16 breaths/minute; among the subgroup ultimately admitted for AE-COPD, baseline DRR was 15.2. In the 5 days prior to an AE-COPD admission, their DRR increased to 19.1, but no meaningful change in DRR was seen in patients not requiring hospital admission. DRR may provide a new window into early identification of AE-COPD.
CKD: Consistency of GFR and Albuminuria as Risk Predictors
Source: Hallan SI, et al. JAMA 2012;308: 2349-2360.
Clinicians have become increasingly aware of the disease burden associated with chronic kidney disease (CKD), especially since the routine inclusion of a calculated estimated glomerular filtration rate (eGFR) within metabolic profile testing. Promulgation of CKD stages by national organizations and encouragement of clinicians to consider referral of patients with CKD at an earlier stage (usually by CKD stage 3-B) has prompted the clinical community to address eGFR as well as the presence, absence, and severity of urinary albumin excretion on a more consistent basis. Because of inherent renal functional decline associated with increased age, accompanied by decrease in muscle mass that contributes to the generation of creatinine, some have questioned whether current stratification of CKD by eGFR, albuminuria, or both holds true throughout the lifespan.
Hallan et al performed a meta-analysis on data from more than 2 million individuals in Asia, Australasia, Europe, and North/South America to investigate whether eGFR and the presence of albuminuria remain consistently predictive of adverse outcomes.
Although at older ages the absolute risk imparted by CKD was greater than in younger folks (simply because a larger absolute number of older individuals die than younger individuals, whether or not they have CKD), overall, the hazard ratio (HR) for mortality decreased with increasing age. For example, at an eGFR of 45 mL/min, the HR for death (when compared to a normal eGFR) was 3.5 for persons ages 18-54, 2.2 for ages 55-64, and 1.35 for ages > 75 years. A similar relationship was noted for albuminuria.
Albuminuria and reduction in eGFR are associated with adverse outcomes throughout the lifespan, although the HR for risk appears to lessen as we age.
Changing Outcomes for Patients with Chronic Hepatitis C
Source: van der Meer AJ, et al. JAMA 2012;308:2584-2593.
Chronic Hepatitis C (HEPC) has an increased risk for liver cancer, end-stage liver disease, and all-cause mortality. Fortunately, current antiviral treatments for HEPc (e.g., ribavirin and interferon) are effective in the majority of subjects. As many as 80% of HEPc patients who complete a therapeutic course will obtain what is called a sustained virological response (SVR); that is, no detectible HEPc virus 6 months after completion of therapy. SVR might reasonably be titled "cure," since indications are that absence of virus at 6 months is indicative of permanent eradication.
Nonetheless, some patients enjoying SVR already have experienced inflammatory hepatic changes resulting in fibrosis. It has not been sufficiently elucidated whether achievement of SVR ultimately reduces risk for mortality, liver cancer, or hepatic failure, especially in a group with already established hepatic fibrosis.
Using an international multicenter database (n = 540), the outcomes of HEPc patients with long-term follow-up (mean 8.4 years), as well as biopsy-proven fibrosis, were investigated to compare those who attained SVR vs those who did not. The mortality rate was essentially three times greater in those who did not attain SVR (26% vs 8.9%); the comparative cumulative incidence rate of liver-related mortality or transplantation was even more dramatic: 1.9% (SVR) vs 27.4% (SVR not attained). The attainment of SVR is associated with substantial long-term reductions in mortality as well as less need for liver transplantation.
Is Fructose a Primary Culprit in Obesity?
Source: Page KA, et al. JAMA 2013;309: 63-70.
Sorting out the causes of the current pandemic of obesity has not been easy and appears to have contributions from various life quadrants: activity, genetics, absolute calorie ingestion, and — most recently — characteristics of the calories we ingest. For instance, whereas in the recent past one might simplistically think that a gram of ice cream and a gram of broccoli should result in similar metabolic impact, recognition of the glycemic index (variation in glucose rate of absorption from different food sources) has taught us that a calorie is not necessarily always a calorie in the grander scope of things.
Fructose, an increasingly commonplace component of fast foods, snacks, etc., has recently come under fire as a potential culprit exacerbating the obesity pandemic. Mechanistically, fructose could be metabolically detrimental because (compared to glucose, that is) it blunts satiety-inducing GLP-1, and fails to shut off appetite-stimulating ghrelin.
Page et al measured regional cerebral blood flow in response to glucose and fructose ingestion. They found that fructose did not produce the same reduction in hypothalamic cerebral blood flow (associated with satiety and fullness) as did glucose. Disproportionate consumption of fructose may be a significant contributor to weight management problems.
When One Antihypertensive Med is Not Enough: Which Combination?; Vitamin D for Osteoarthritis: NOT; Early Identification of COPD Exacerbations; CKD: Consistency of GFR and Albuminuria as Risk Predictors; Changing Outcomes for Patients with Chronic Hepatitis C; Is Fructose a Primary Culprit in Obesity?You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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