Lower Blood Pressure, Not the Drug Regimen, Regresses Left Ventricular Hypertrophy

May 13, 2009

May 13, 2009 (San Francisco, California) — Getting blood-pressure levels down to targets recommended in the clinical guidelines regresses left ventricle hypertrophy (LVH) in patients with resistant hypertension. This benefit, importantly, was not limited to patients treated with angiotensin-renin antagonists but occurred regardless of which drug combination clinicians used to lower blood pressure.

The main message for the clinician is that they should use agents that bring the blood pressure down to levels that the guidelines recommend.

These new data support the concept that previously described differences in LVH regression between antihypertensive agents are abolished when recommended blood-pressure goals are achieved, say researchers.

"This is a trial that I think has practical implications for physicians," said lead investigator Dr Alan Miller (University of Florida Health Science Center, Jacksonville, FL). "Basically, what we've shown using three different combinations of drug regimens is that we were not only able to bring blood pressure down to recommended guideline cut points, but we were also able to cause reverse remodeling of the ventricle."

Blood Pressure Goals, Not the Drug Regimen

Presenting the results of the Comparable Blood Pressure Control and Left Ventricular Mass Reduction (CLEVER) trial here at the American Society of Hypertension 2009 Scientific Meeting last week, Miller said it is believed that the angiotensin-renin agents with neurohormonal antagonism and vasodilation, which include angiotensin-receptor blockers (ARBs) and ACE inhibitors as well as calcium-channel blockers, are best at regressing LVH. Diuretics and beta blockers, on the other hand, are thought to be less effective in this regard.

LVH is present in approximately 30% of patients with hypertension and is associated with an increased risk of cardiovascular morbidity and mortality.

In this study, the researchers wanted to assess left ventricular remodeling in 287 patients with hypertension and LVH who were treated to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) targets.

Prior to drug therapy, patients were screened with 2D echocardiography to confirm LVH. Once confirmed, all patients were treated with low-dose lisinopril--10 mg for one week and 20 mg in the second week--before undergoing cardiac MRI. Patients were then randomized to one of three treatment arms: open-label lisinopril only, open-label carvedilol and lisinopril, or open-label atenolol plus lisinopril. The mean doses of the lisinopril, atenolol, and carvedilol used in the study were 29 mg, 82 mg, and 60 mg, respectively. For patients who didn't reach blood-pressure targets, the protocol allowed concomitant use of the diuretic hydrochlorothiazide 12.5 to 25 mg or the addition of the calcium-channel blocker amlodipine at a dose of 5 to 10 mg.

Blood Pressure and LVH Results in Patients With Readable MRI Images

Blood-pressure measurements Lisinopril (n=59) Atenolol plus lisinopril (n=76) Carvedilol plus lisinopril (n=66)
Mean baseline systolic/diastolic blood pressure (mm Hg) 147.1/91.4 149.8/89.5 150.5/89.5
Mean systolic/diastolic blood pressure at 12 mo (mm Hg) 126.3/80.4 128.8/76.5 125.9/78.0
Patients who achieved guideline targets (%) 79 67 73
Primary end point: Change in left ventricular mass assessed my MRI at 12 mo (gm/m2) -7.9 -6.7 -6.3

After 12 months, all three treatments significantly reduced systolic and diastolic blood pressures from baseline. In terms of left ventricular mass assessed by MRI, there was no significant difference in reductions from baseline between the treatment arms.

"The main message for the clinician is that they should use agents that bring the blood pressure down to levels that the guidelines recommend at this point in time," said Miller. "When you get to the guidelines, good things are going to happen. In the case of our study, it's LVH regression, and I would suspect that clinical outcomes would follow."

Miller noted that improvements in LVH were observed in all subgroups, including 25% of patients with diabetes mellitus. He said there was no difference in adverse events between the treatment groups, although patients treated with the beta blocker atenolol did have lower heart rates and reported more fatigue than the other treatment arms. He said the study, in addition to the overall findings, showed that beta blockers are effective drugs when used with vasodilators for lowering blood pressure.

GlaxoSmithKline sponsored the CLEVER trial, and Miller reports consulting for the company.