Clinical Briefs
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
Hepatitis C: Shorter, Successful Treatment
Source: Kowdley KV, et al. N Engl J Med 2014;370:20:1879-1888.
The current and future epidemiologic burden of hepatitis C virus (HCV) is increasingly recognized as a major public health issue. Even though the greatest wave of liver disease attributable to HCV could be ahead of us, even now HCV is the most common cause of chronic liver disease, liver transplantation, and hepatic carcinoma in the United States. Because of insufficient identification of at-risk persons based on risk-factor profiles alone, the CDC has recommended that clinicians screen all persons born from 1945-1965 for HCV.
Supporting such initiatives is the recent evolution of treatment regimens characterized by higher success rates, greater efficacy in resistant subgroups, better tolerability, and more consistent across-genotype applicability than prior regimens.
Genotype 1 among HCV patients has been noted to be relatively refractory to older treatment regimens. Recently, a highly effective regimen combining ledipasvir (LED) and sofosbuvir (SOF) for 12 weeks demonstrated cure (i.e., sustained viral response, defined as absence of detectable HCV for at least 6 months post-treatment) in more than 95% of this highly resistant group.
To evaluate the potential efficacy of an even shorter course, Kowdley compared LED + SOF (8 weeks) vs LED + SOF (12 weeks) vs LED + SOF + ribavirin (12 weeks). They determined that not only was the LED + SOF 8-week course non-inferior to 12 weeks of the same, but that ribavirin imparted no meaningful additional efficacy and was associated with more adverse effects. Patients with HCV can look forward to a variety of highly effective, well tolerated, short-course treatments.
Can Potassium Prevent Sodium Adversities?
Source: Rodrigues SL, et al. J Am Soc Hypertens 2014;8:232-238.
On an epidemiologic basis, it is clear that for most populations there is a linear risk between levels of salt intake and cardiovascular (CV) endpoints, directly related — it appears — through the impact on blood pressure (BP). While it is intuitive as well as enticing to assume that the linear relationship between salt-BP-CV disease should be a two-way street, convincing proof of that has been remarkably elusive; that is, we do not have evidence from a large, randomized clinical trial proving that dietary sodium reduction improves CV outcomes. Nonetheless, since there is no suggestion that elevated ingestion of sodium is a health benefit, most experts advocate that a population-wide reduction in sodium, most of which excess comes from processed foods with lesser nutritional value than fresh food, would be a good thing.
There are, however, flies in the ointment. For instance, some individuals appear to ingest large amounts of sodium without incurring BP increases. Why that might be was explored by Rodrigues et al in a population of Brazilians (n = 1285). Investigators compared the amount of salt intake per day and evaluated potassium intake with the hunch that higher potassium levels in the diet might protect against sodium-induced elevations in BP. Their supposition was quite sensible based on two earlier population studies which found that BP was inversely associated with dietary potassium intake.
Among persons consuming high levels of sodium (> 6 gm/d), those in the top quartile sodium/potassium ratio had mean SBP 8 mmHg higher than the lowest quartile. Similarly, the highest quartile of dietary potassium intake had SBP that was 6 mmHg lower than the lowest quartile.
Having a strong component of potassium in the diet appears to mitigate sodium-associated elevations in BP.
SGLT2 Inhibitors and Blood Pressure
Source: Baker WL, et al. J Am Soc Hypertens 2014;8:262-275.
It has not gone unnoticed that there are multiple competing pathologies in diabetes that weigh as heavily or even more heavily on the scale of risk factors than glucose. Glucose control has not been shown to improve macrovascular outcomes (MI, stroke). On the other hand, BP control and lipid control have been shown to have more broad favorable impact, extending beyond microvascular endpoints to include macrovascular benefit. SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin), in addition to lowering glucose by enhancing urinary glucose excretion, are also associated with BP reduction, a combination that has great appeal since diabetics suffer a disproportionate burden of hypertensive cardiovascular disease.
Baker et al performed a meta-analysis of the BP effects of SGLT2 inhibitors. Their data analysis included not only agents FDA-approved for use in the United States, but also agents with data reported in Phase 2 and 3 clinical trials not yet approved in the United States (e.g., empagliflozin, ipragliflozin, remogliflozin).
From clinical trial data, SGLT2 inhibitors reduce SBP by a mean of 4 mmHg. While this may seem a modest amount, it should be recognized that the population studied was not exclusively hypertensive. Rather, the baseline SBP mean among the 27 trials they assessed (n = 12,960) ranged from 123-140 mmHg. In addition to their favorable effects upon glucose, SGLT2 inhibitors favorably affect BP.
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