RESUMO
BACKGROUND AND PURPOSE: The HOPE-3 trial (Heart Outcomes Prevention Evaluation3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. METHODS: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. RESULTS: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.591.08]), ischemic stroke (HR, 0.80 [95% CI, 0.551.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.341.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.412.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.520.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.370.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.592.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.572.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.360.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.230.72]). CONCLUSIONS: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
Assuntos
Feminino , Acidente Vascular Cerebral/prevenção & controle , Anti-Hipertensivos , Inibidores de Hidroximetilglutaril-CoA RedutasesRESUMO
An international double-blind, parallel-group,randomized controlled trial was performed to determinethe efficacy and safety of a new first-line strategy in mildto moderate hypertension based on a single-pillcombination of perindopril/amlodipine versus a validatedstepped-care strategy (initiation with valsartanmonotherapy, up-titrating to valsartan/amlodipine after2 months).Methods: At inclusion, patients received perindopril/amlodipine 3.5/2.5mg or valsartan 80 mg. At 1, 2, and3 months, patients were up-titrated if they haduncontrolled hypertension ( 140/90 mmHg). The uptitrationsteps were: perindopril/amlodipine 7/5 mg,14/10 mg, and 14/10mg R indapamide sustained release1.5 mg; or valsartan 160 mg, valsartan/amlodipine160/5 mg, and 160/10 mg. The two groups were similarat baseline (55.5 years, 53% men, blood pressure163.5/100.2 mmHg); 881 perindopril/amlodipine and876 valsartan/amlodipine patients were analyzed forefficacy.Results: After 1 month, the rate of controlledhypertension was 33% with perindopril/amlodipine versus27% with valsartan/amlodipine (estimate of difference,R6.1%; P»0.005); this between-strategy differenceremained significant at every visit (P<0.05). After 3months, blood pressure was 137.8 12.4/83.3 8.7 and139.7 13.3/84.8 9.0 mmHg, respectively, with greaterreductions from baseline with perindopril/amlodipine(primary endpoint 2.0/ 1.5 mmHg; both P<0.001).Similar results were observed at all other visits (allP 0.001). The safety of the two strategies wasequivalent.Conclusions: The three-step strategy of initiation withsingle-pill perindopril/amlodipine produces greaterreductions in blood pressure, and better and quicker ratesof control of hypertension. This can be expected to beassociated with benefits beyond blood pressure control,notably improved compliance and better cardioprotection.Keywords: amlodipine, hypertension, perindopril, singlepillcombination, valsartan...