New Standard in BP Lowering

LIFE study results showing losartan's added protection can change physician's view of hypertension treatment

People have repeatedly been told: lifestyle diseases are alarmingly on the rise. People continue to be unmindful of their health-eating unhealthily, smoking, adopting a sedentary lifestyle. Because of this, more and more people fall ill with--and even die of--cardiovascular diseases everyday, and the ones who are not yet sick are at an increased risk of developing these conditions.

    That is why health professionals have always stressed that to prevent these conditions from even starting, what one has to do is adopt a healthy diet, avoid smoking, and start getting physically active. This way, one's health is protected right from the start.a

    However, people continue with their unhealthy lifestyles. So they develop conditions that could be fatal if left unchecked. One of the most alarming of these conditions is hypertension, which, apart from being one of the leading causes of sickness in the country, is one of the more significant conditions that lead to a heart attack or stroke, among other cardiovascular events and complications.

    This is where the concept of secondary prevention--keeping a condition from worsening--comes in. In April Merck, Sharpe, and Dohme Philippines introduced to the media one of the most significant clinical trials in the control of hypertension and therefore protection from heart attacks, stroke, and even cardiovascular death.

Selective Blocking

    The results of the landmark trial, Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, were presented by Dr. Eugenio Reyes, a member of the Philippine Heart Association Council on Preventive Cardiology, and Dr. Esperanza Cabral, clinical professor at the University of the Philippines College of Medicine and former president of the Philippine College of Physicians and Philippine Heart Association.

    The LIFE trial, the results of which were published by The Lancet in March and presented at the 51st annual meeting of the American College of Cardiology, involved nearly 9,200 hypertensive patients from the United States, United Kingdom, and Scandinavia.

    The randomized, double-blind, parallel group trial was undertaken to see whether the selective blocking of angiotensin II would have any significant effect in lowering the risks for cardiovascular disease and death among hypertensive patients who also have left ventricular hypertrophy. Until the LIFE study, the best-documented treatment in reducing the combined risk of cardiovascular disease and death involved beta-blockers and diuretics.

    Spanning four years, the LIFE study involved patients who were assigned losartan on the one hand, and the beta-blocker atenolol, on the other. The patients ranged from 55 to 80 years old, and had an average blood pressure of 174/98 mm Hg.

    By the end of the study, there was a significant reduction in the blood pressure of the patients in both groups. Nearly half of all the participants have a blood pressure of 140/90 mm Hg or lower.

New Standard

    Significantly, the reduction of the combined risk for cardiovascular death, stroke, and myocardial infarction was achieved with losartan by 13 percent (p=0.021). Dr. Björn Dahlöf, lead investigator of the trial, said: "Results of the LIFE study showed that losartan has set a new standard in the treatment of hypertension."

    Explaining their choice of atenolol as comparative drug, the authors said that beta-blockade alone or in combination with diuretics had been shown better than placebo in trials of antihypertensive drugs and secondary prevention among MI survivors.

    The Swedish Trial in Old Patients with hypertension (STOP), for instance, yielded 40 percent reduction in primary composite endpoint of cardiovascular morbidity and mortality with an event rate similar to that attained in the atenolol group of the LIFE study. Other placebo-controlled studies reduced rates of many cardiovascular events by 15 to 45 percent.

    "Thus, the further 13 percent reduction of the primary endpoint by losartan in our trial should be seen as an incremental benefit above the established effects of beta-blockade," the authors wrote in The Lancet.

    As for individual end points, losartan and atenolol proved equally effective in reducing the risk for fatal and nonfatal myocardial infarction as well as cardiovascular death. Both groups achieved an 11.4-percent reduction in cardiovascular mortality. While in the reduction of MI events, the rate was about 7.3 percent.

    The big difference between the losartan and atenolol groups came in the risk reduction for fatal and nonfatal strokes--losartan is 24.9 percent (p=0.001) more efficacious than atenolol. Also, the risk of developing diabetes in hypertensive patients is much lower with losartan than with atenolol by 25 percent (p=0.001).

    As for adverse events, fewer patients in the losartan group dropped out of the study compared with those on atenolol, showing losartan's better tolerability.

    The results, the study authors said, contrast with those from other studies comparing ACE inhibitors, calcium antagonists, and alpha blockers with beta-blockers or diuretics or both, in which primary outcomes did not differ.

    "Our results show that losartan reduces cardiovascular morbidity and mortality more than established antihypertensive drug (atenolol)," they said.

    The study also noted that the greater clinical benefit in high-risk patients and enhanced tolerability with losartan than atenolol suggest that broader application will improve outcome for hypertensive patients.

    "Our results are directly applicable in clinical practice and should afffect future guidelines," the authors concluded.

    Dr. Reyes said that the results of the LIFE trial are significant in that they are also bound to change doctors' view in lowering blood pressure. "Before, most doctors were content with just lowering the patient's blood pressure and that the choice of medication didn't really matter. With the results of the LIFE trial, clinical experts say that how you lower blood pressure can be just as important."

    Dr. Cabral agreed, saying that people developing hypertension could be compared to people crossing the street. The pedestrian lane provides pedestrians protection; a beta-blocker, she said, functions like a pedestrian lane by protecting hypertensive patients from cardiovascular disease.

    "While the pedestrian lane reduces the risk of people being hit by car," she added, "a traffic aide further provides the pedestrian protection from an accident. Losartan is like that traffic aide, offering hypertensive patients further reduction from risk of cardiovascular complications."