Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Peripheral Artery Disease: Helping Patients to Walk the Walk

Source: Ahimastos AA, et al. JAMA 2013;309:453-460.

Currently available treatments forperipheral artery disease (PAD) are only modestly effective. PAD portends increased risk of cardiovascular disease; hence, most PAD patients should be receiving pharmacotherapy with a statin and an antiplatelet agent (usually clopidogrel).

Because one of the quality-of-life limiting factors in advanced PAD is disease-mediated diminution in walking distance and walking time, incorporation of pharmacotherapy to improve these limitations is also considered important. Unfortunately, the two FDA-approved treatments (pentoxifylline and cilostazol) for symptoms of PAD provide only a modest increase in walking distance (25% or less). Smoking cessation and exercise advice remain critically important, but are too often not heeded.

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that has been used in numerous major clinical trials, including the HOPE trial, ONTARGET trial, REIN trial, and others. Use of ramipril is usually predicated on 1) its ability to lower blood pressure, 2) its ability to improve outcomes in congestive heart failure, or 3) its ability to improve albuminuria.

Based on results seen in a small pilot trial that suggested favorable results of ramipril on treadmill time in subjects with PAD, Ahimastos et al performed a larger randomized clinical trial (n = 212).

At the conclusion of the 6-month trial of ramipril 10 mg/day vs placebo, pain-free walking time had increased by more than 50% in the ramipril group, but only 10% in the placebo group.

Although the mechanism for improved function is speculative, it has been noted that ACE inhibitors increase skeletal muscle blood flow; indeed, this has been the mechanism to which improved insulin sensitivity in diabetics has been attributed. Ramipril may offer a new avenue to improve functionality in patients with PAD.


Long-Term Functional Outcomes After Localized Prostate Cancer Treatment

Source: Resnick MJ, et al. N Engl J Med 2013;368:436-445.

When prostate cancer is localized, either radical prostatectomy (RPT) or external beam radiation (EBR) can often be curative. The adverse effect profile of these two interventions, however, may be meaningfully different and such differences might also be time-dependent.

Resnick et al studied men (n = 1164) from the Prostate Cancer Outcomes Study who had been enrolled between the ages of 55-74 and had localized prostate cancer. More than 80% of the men had a Gleason score of 7 or less. The prevalence of urinary incontinence (UI) and erectile dysfunction (ED) were compared among these men at years 2, 5, and 15.

Prostatectomy subjects were five to six times more likely to have incontinence at 2 years and 5 years than EBR subjects. Similar disadvantage was seen in the prevalence of ED (two- to four-fold increased incidence in the RPT group). At the 15-year conclusion of their observations, no differences between groups remained. However, one would anticipate, for instance, a substantial incremental increase in ED as men age with or without intervention; hence, the fact that between-group differences are eliminated by 15 years provides little solace for the men who suffer the adverse effects in the interim!


A Relationship Between Nocturia and Hypertension

Source: Feldstein CA. J Am Soc Hypertens 2013;7:75-84.

Nocturia could easily be misconstrued as a “nuisance” symptom since, after all, nobody dies from nocturia ... or do they? Indeed, urinary frequency and nocturia have been associated with greater risk for nocturnal falls and hip fracture; hence, nocturia can be much more than just a nuisance.

Clinicians are used to identifying nocturia as a symptom associated with benign prostatic hyperplasia, overactive bladder, uncontrolled diabetes, uncontrolled congestive heart failure, use of diuretics, and (less commonly) interstitial cystitis. What is only minimally recognized, however, is the emerging observation that hypertension is associated with nocturia.

Several plausible mechanisms can explain the nocturia/hypertension relationship: hypertension-induced alterations in glomerular filtration or tubular transport, activation of atrial natriuretic peptide from ventricular wall stress induced by hypertension, and resetting of the pressure-natriuresis relationship in the kidney, to name a few.

Feldstein indicates that the prevalence of nocturia in untreated hypertension patients may be as high as 33%. Since nocturia can be both a burdensome symptom and lead to significant morbidity (and mortality), clinicians may wish to specifically inquire about nocturia when encountering hypertension patients.