Left Ventricular Hypertrophy a Major Risk Factor for Heart Attack
Drug Reduces Blood Pressure and LVH over Long Term
Sep 22, 2004
For patients with a dangerous enlargement of heart muscle called left ventricular hypertrophy (LVH), the drug Losartan beats standard beta-blocker therapy in reducing hearts to a healthier size, according to researchers at NewYork Presbyterian Hospital/Weill Cornell Medical Center.
The study, published in the September 14 issue of Circulation, finds that Losartan's effects on LVH go beyond its ability to lower blood pressure — suggesting that added mechanisms may be at work.
"Overall there was an advantage in favor of Losartan," a drug from the angiotensin II receptor antagonist family of cardiovascular medications, said study lead researcher Dr. Richard B. Devereux, Professor of Medicine in the Greenberg Division of Cardiology at Weill Cornell Medical College, and Attending Physician at NewYork-Presbyterian/Weill Cornell.
"This is the largest well-controlled, well-designed study comparing the ability of two now standard anti-hypertensive treatments to reduce the weight of the left ventricle as measured by echocardiogram — with both drugs producing essentially identical blood-pressure lowering. However, Losartan significantly improved on reductions in LVH compared with the beta-blocker, Atenolol," Dr. Devereux said.
The study is part of the larger Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, a multicenter investigation of 9,193 European and American patients with high blood pressure and LVH as revealed on echocardiogram.
LVH is intimately related to a history of hypertension, as the heart thickens over time to cope with increased blood pressure. Enlarged heart muscle is also a serious risk factor for heart attack and stroke.
In this arm of the LIFE study, Dr. Devereux and colleagues compared the LVH of 960 patients 1, 2, 3, 4, and 5 years after being randomized to receive either Atenolol or Losartan therapy.
"One of the strengths of the study was that patients had their blood pressure checked in the doctor's office an average of 15 times, so there's a lot of information on hypertension," Dr. Devereux said.
The researchers found that both drugs acted similarly in reducing blood pressure over the 5-year period.
However, Losartan patients showed significantly better reductions in LVH, compared with patients on the beta-blocker. "The walls of their hearts got thinner with Losartan," Dr Devereux explained.
He explained that beta-blockers like Atenolol "slow the pulse, making the heart pump a little more blood on each heartbeat, so the heart often tends to enlarge slightly when beta-blockers are used."
On the other hand, Losartan works on a different mechanism, so "it thins the heart walls somewhat better than Atenolol and prevents the increase in heart size we'd seen with that drug."
The study also found that while the anti-hypertensive benefits of either drug leveled out after the first year or two, Losartan's healthy effects in reducing left ventricular size continued to increase with years of use. "It seems like you have cumulative benefits with Losartan," Dr. Devereux said.
This study builds on previous findings from the LIFE trial, including a study led by Dr. Devereux and released last year in The Annals of Internal Medicine. That investigation found Losartan better at preventing cardiovascular events in hypertensive patients with LVH, compared with Atenolol.
"Excess amounts of heart muscle are very strong predictors of a high risk of cardiovascular events such as heart attack or stroke," Dr. Devereux noted. "So the finding that one treatment reduces heart muscle weight more than another has very important clinical implications."
The study was funded by a grant from Merck & Co.
Co-researchers include Dr. Kristian Wachtell, also of Weill Cornell Medical College and Glostrup University Hospital, in Glostrup, Denmark; Dr. Bjorn Dahlof, of Sahlgrenska University Hospital and the University of Goteborg, Sweden; Dr. F. Eva Gerdts, of Haukeland University Hospital, Bergen, Norway; Dr. Kurt Boman, of Skellefteå Lasarett and Umea University, Skelleftea, Sweden; Dr. Markku S. Nieminen, of Helsinki University Central Hospital, in Helsinki, Finland; Dr. Vasilios Papademetriou, of Veterans Administration Hospital, Washington, DC; and Dr. Jens Rokkedal, of Glostrup University Hospital, Glostrup, Denmark.