ASCOT: Amlodipine outperforms atenolol in stroke prevention
Long-term results from the ASCOT trial demonstrated that an amlodipine-based BP-lowering regimen reduced stroke risk compared with an atenolol-based regimen, although no benefit in dementia risk was observed.
Since management of stroke risk factors may reduce later dementia, William N. Whiteley, PhD, Scottish senior clinical fellow in Centre for Clinical Brain Sciences at the University of Edinburgh, U.K., and colleagues evaluated whether dementia or stroke were linked to different BP-lowering regimens; atorvastatin or placebo; and mean BP, BP variability and mean cholesterol levels.
In the ASCOT trial, patients with hypertension and at least three CVD risk factors were randomly assigned to an amlodipine- or atenolol-based BP-lowering regimen targeting a BP less than 140/90 mm Hg for 5.5 years. The researchers also randomly assigned patients with total cholesterol of 6.5 mmol/L or less to atorvastatin 10 mg or placebo for 3.3 years.
Of the 8,580 U.K. participants, researchers followed 7,300 for up to 21 years from randomization, with a median follow-up of 17 years. The mean age was 64 years, and most patients were men (81% in BP-lowering arm; 87% in lipid-lowering arm).
Results revealed that atorvastatin use for 3.3 years failed to affect stroke (adjusted HR = 0.92; 95% CI, 0.78-1.09; P = .341) or dementia (aHR = 0.98; 95% CI, 0.82-1.18; P = .837) compared with placebo. No associations between mean total cholesterol and later stroke or dementia were reported.
Moreover, compared with an atenolol-based regimen, an amlodipine-based regimen for 5.5 years lowered the risk for stroke (aHR = 0.82; 95% CI, 0.72-0.93; P = .003) but not dementia (aHR = 0.94; 95% CI, 0.82-1.07; P = .334) during follow-up.
In other data, BP variability conferred a higher risk for dementia (HR per 5 mm Hg = 1.14; 95% CI, 1.06-1.24; P < .001) and stroke (per 5 mm Hg, HR = 1.21; 95% CI, 1.12-1.32; P < .001), adjusted for mean BP.
“Higher BP variability,” the researchers wrote, “is largely due to age-related stiffening of large arteries and loss of baroreflex function. Antihypertensive drugs have little beneficial effect in reducing variability, although dihydropyridine calcium channel blockers may have a modest effect.”
In conclusion, they wrote: “We demonstrate the importance of BP control with amlodipine rather than atenolol for stroke prevention and that starting amlodipine about 5 years earlier still has an important detectable effect on stroke incidence over 20 years. Despite this reduction in stroke in incidence, there was no reduction in dementia incidence, although dementia was almost as frequent as stroke over follow-up.”