Key result
Losartan cuts major cardiovascular events ~13% vs atenolol in patients with hypertension and LVH.
Why the study?
It was unknown whether selective blocking of angiotensin II improves left ventricular hypertrophy beyond blood pressure reduction and consequently reduces cardiovascular morbidity and death.
Does once daily losartan-based antihypertensive treatment reduce cardiovascular morbidity and death compared to atenolol-based treatment in patients aged 55-80 years with essential hypertension and LVH?
RCT (n=9,193)
double-masked
randomised
Does once daily losartan-based antihypertensive treatment reduce cardiovascular morbidity and death compared to atenolol-based treatment in patients aged 55-80 years with essential hypertension and LVH?
Relative Risk: 0.87 (95% CI 0.77–0.98)
Absolute Event Rate: 23.8% vs 27.9%
p-value: p=0.021
Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure in patients with essential hypertension and LVH, primarily driven by a reduction in stroke.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“I think we have this paradigm shift in the thinking of hypertension, that it's not only necessarily blood pressure control, we also need target organ damage control to achieve the disease control.”
“This is the first demonstration that a treatment can reduce illness and death in ISH patients better than another treatment that is equally good at reducing blood pressure. The finding of a 40 percent reduction in stroke is especially important, because of stroke's role as a major cause of death and disability in people with hypertension.”
Favors losartan over atenolol in hypertensive LVH; confirms cardiovascular protection beyond blood pressure reduction.
BACKGROUND: Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension. Left ventricular hypertrophy (LVH) is a strong independent indicator of risk of cardiovascular morbidity and death. We aimed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and, consequently, reduces cardiovascular morbidity and death. METHODS: We did a double-masked, randomised, parallel-group trial in 9193 participants aged 55-80 years with essential hypertension (sitting blood pressure 160-200/95-115 mm Hg) and LVH ascertained by electrocardiography (ECG). We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event (death, myocardial infarction, or stroke). We used Cox regression analysis to compare regimens. FINDINGS: Blood pressure fell by 30.2/16.6 (SD 18.5/10.1) and 29.1/16.8 mm Hg (19.2/10.1) in the losartan and atenolol groups, respectively. The primary composite endpoint occurred in 508 losartan (23.8 per 1000 patient-years) and 588 atenolol patients (27.9 per 1000 patient-years; relative risk 0.87, 95% CI 0.77-0.98, p=0.021). 204 losartan and 234 atenolol patients died from cardiovascular disease (0.89, 0.73-1.07, p=0.206); 232 and 309, respectively, had fatal or non-fatal stroke (0.75, 0.63-0.89, p=0.001); and myocardial infarction (non-fatal and fatal) occurred in 198 and 188, respectively (1.07, 0.88-1.31, p=0.491). New-onset diabetes was less frequent with losartan. Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated. Losartan seems to confer benefits beyond reduction in blood pressure.
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Dahlöf et al. (2002) conducted an RCT in essential hypertension and left ventricular hypertrophy (n=9,193). losartan vs. atenolol was evaluated on primary cardiovascular event (death, myocardial infarction, or stroke) (RR 0.87, 95% CI 0.77-0.98, p=0.021). Losartan reduced the primary composite of cardiovascular death, myocardial infarction, or stroke compared to atenolol (RR 0.87; 95% CI 0.77-0.98; p=0.021) in patients with hypertension and LVH.
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