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  • Multiple Sclerosis Symposium and American Society of Hypertension: Valsartan


A large-scale clinical trial comparing the ARB valsartan with the same ARB plus HCTZ revealed unexpected findings and raised new questions. The ARB/HCTZ combination lowered BP successfully but significantly increased the inflammatory marker hsCRP Professor Paul Ridker, MD, MPH, study author of the Val-MARC trial (POzlsartan: Managing BP Aggressively and Evaluating deductions in hsCRP) from Brigham and Women’s Hospital in Boston, had earlier shown that hsCRP interacts with elevated BP to increase cardiovascular risk, predicting incident hypertension, heart attacks, and strokes in normotensive individuals. Angiotensin II is also known to be a potent pro-inflammatory mediator, and ARBs have been reported to reduce hsCRP. However, he commented that biomarkers are a “difficult story,” particularly when it comes to “figuring out what is clinically useful.”

The stakes are substantial, he added, at a Novartis-supported symposium, “Prevention of Hypertension,” and in an oral session at the ASH meeting. Patients with low low-density lipoprotein-cholesterol (LDL-C) levels but high CRP levels—a group representing about 25% of the U.S. population—are at higher cardiovascular risk than individuals with high LDL levels and low CRP levels. That “high CRP group,” he added, has become a focus for reducing BP and cardiovascular events.

The first major unknown: Is hsCRP a risk marker or a risk factor?

The objective of the randomized Val-MARC trial was to determine the answer to an essential but more preliminary question: Do the effects of ARBs on hsCRP concentrations result from systemic intravascular pressures, or are they are independent of BP reductions?

In the trial, 1,668 patients with a BP of 160-185/100-109 mm Hg received once daily (with a forced titration to 320 mg once daily) or the same valsartan dose plus HCTZ at 12.5 mg once daily (which could be doubled at week 12 at the physician’s discretion). The primary endpoint was a change in BP or hsCRP at week six.

At the sixth week, patients receiving valsartan plus HCTZ had mean reductions of 25 mm in Hg systolic BP and 14 mm Hg in diastolic BP that were significantly greater (P < .001) than patients receiving valsartan alone. For the valsartan-alone group, the average systolic BP was reduced by 18 mm Hg systolic and the average diastolic BP was reduced by 9 mm Hg.

Changes in hsCRP, however, diverged in the two groups: patients experienced a 9% reduction with valsartan mono-therapy and an increase greater than 4% (P < .001) with ARB/HCTZ. The anti-inflammatory effects of valsartan were maintained at 12 weeks.

Dr. Ridker concluded that canadian valsartan anti-inflammatory effects appeared to be independent of BP reductions and “may be neutralized by HCTZ.” He also stated:

“An aggressive strategy, utilizing combination therapy in patients with early stage 2 hypertension, resulted in substantially greater blood pressure reductions, potentially reducing atherosclerotic risk.”

The possibility of contradictory therapeutic implications is striking and raises another key question: Will the Val-MARC trial’s finding of lowered inflammation, independent of BP reduction with valsartan monotherapy, translate to net clinical advantages?

“That,” Dr. Ridker answered, “will require well-designed prospective trials.”

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