| |
 |
| TITLE |
|
Telmisartan, ramipril, or both in patients at high risk for vascular events.
|
|
|
| AUTHORS |
|
The ONTARGET Investigators, Salim Yusuf, Koon K Teo, Janice Pouge, Leanne Dyal, Ingrid Copland, Helmut Schumacher, G Dagenais, P Sleight, Craig Anderson
|
|
|
| PUBLICATION INFORMATION |
Journal Name: The New England Journal of Medicine
Volume: 358(15)
Pages: 1547-59
Date Published: 04/10/2008
|
|
|
| ABSTRACT/REVIEW |
What were the researchers trying to learn in this study? They wanted to see if a newer high blood pressure drug called telmisartan (tel mi SAR tan) was as safe and effective as an older drug called ramipril (RAM eh pril). They also wanted to see if the combination of telmisartan and ramipril was more effective than either drug alone.
Telmisartan is a high blood pressure drug belonging to the class of drugs called angiotensin II receptor blockers (ARBs). These drugs interfere with the action of a natural substance (angiotensin II) produced in the body that causes blood vessels to constrict and raise blood pressure. Telmisartan is marketed under the brand name Micardis®.
Ramipril (Altace®) is an angiotensin converting enzyme (ACE) inhibitor. ACE inhibitors work by blocking an enzyme that is necessary to produce the blood vessel constricting substance angiotensin II. As a result, the blood vessels relax and this lowers blood pressure.
The primary measure of effectiveness in this trial was the total deaths from heart and blood vessel-related (cardiovascular) causes, heart attacks (myocardial infarctions), strokes, and hospitalizations for heart failure for each group.
What did they find? The results of this study showed that telmisartan was "noninferior" or equivalent to ramipril in terms of reducing the risk of death from cardiovascular causes, heart attack, stroke, or heart failure in patients with established blood vessel disease or high-risk diabetes. After a follow-up of about 56 months, 1,412 patients (16.5%) in the ramipril group and 1,423 patients (16.7%) in the telmisartan group had experienced one or more of the outcomes. The difference between these two percentages is not statistically significant, meaning the difference is small enough that the result could have occurred by chance.
When the two drugs were taken together, no added benefit was seen in terms of reducing the risk of adverse cardiac events, but there was an increase in drug-related side effects.
Patients who took telmisartan alone or in combination with ramipril, however, had significantly greater decreases in blood pressure than those who took ramipril alone. At the beginning of the study, the average blood pressure was 141.8/82.1 mmHg. After 6 weeks of treatment, average blood pressure was reduced by 7.4/5.0 mmHg in the telmisartan group, 6.4/4.3 mmHg in the ramipril group, and by 9.8/6.3 mmHg in the combination-therapy group.
Kidney impairment (based on the physician's report of an event that led to discontinuation of the study drug) was seen significantly more often in the combination-therapy group (13.5%) compared to either the telmisartan group (10.6%) or the ramipril group (10.2%).
As expected, those who took telmisartan alone had significantly lower rates of cough compared to those who took ramipril (1.1% versus 4.2%). Fewer patients in the telmisartan (0.1%) experienced episodes of rapid swelling beneath the skin (angioedema) compared to those in the ramipril group (0.3%). Symptoms of low blood pressure (hypotension) occurred more often in telmisartan-treated patients (2.6%) compared to ramipril-treated patients (1.7%). The researchers noted that these hypotensive episodes are consistent with the lower blood pressure levels seen with telmisartan.
Who was studied? The ONTARGET trial enrolled 25,620 patients with blood vessel disease including coronary, peripheral, or cerebrovascular disease or diabetes (with organ damage) plus additional risk factors who were 55 years of age or older. Patients with blood pressure above 160/100 mmHg or with evidence of heart failure were excluded.
A total of 8,576 patients were randomly assigned to receive ramipril, 8,542 received telmisartan, and 8,502 were assigned to receive both drugs (combination therapy). They followed the patients for an average of 55 months.
The average age of the ONTARGET study population was 66.4 years, 73.3% were men, 85% had cardiovascular disease, 69% had high blood pressure (hypertension), and 38% had diabetes.
How was the study done? Participants in the study first underwent a run-in period in which they received increasing doses of the drugs over time to gradually bring them up to the dose to be used for the trial period. Of the 29,019 patients who entered the run-in period, 3,399 were excluded from the study and 25,620 underwent random assignment to a treatment group.
After random assignment, follow-up visits occurred at 6 weeks, at 6 months, and then every 6 months for 5.5 years.
What did researchers know before starting this study? Previous studies have shown that ACE inhibitors (such as ramipril) reduce heart-related adverse events, including death, in patients with vascular disease or high-risk diabetes. However, ACE inhibitors only partially block the production of all angiotensin II and can have side effects such as cough and the rare, but serious side effect of rapid swelling beneath the skin of the hands and the mucous membranes (angioedema).
ARBs (such as telmisartan) block the action of angiotensin II without having the same risk of cough or angioedema. However, the role of ARBs in patients with established vascular disease or high-risk diabetes is unknown. They have been shown to reduce the rate of death or hospitalization for heart failure in patients with heart failure who either could not tolerate an ACE inhibitor or were already taking one.
Why did they do it? The researchers wanted to determine whether daily treatment with telmisartan, either alone or in combination with the widely used ramipril, could reduce the risk of death, heart attack, stroke, or heart failure in high-risk patients with established cardiovascular disease or diabetes.
What did the researchers say their study results mean? The researchers concluded that telmisartan is an effective and well tolerated treatment that reduces the risk of death from cardiovascular causes, heart attack, stroke, or heart failure for high-risk patients with heart disease or diabetes. As compared with ramipril, patients who took telmisartan had fewer episodes of cough or angioedema, but higher rates of hypotensive (low blood pressure) symptoms. The choice between the two drugs will depend on the preferences of the patient and physician and on the individual patient's susceptibility to specific side effects.
In this trial, the combination of telmisartan and ramipril was associated with more adverse side effects without an increase in benefits.
|
|
|
|
|
|
|
