Shantou-Amsterdam study on blood pressure Reduction and dementia Prevention (SHARP)
Dementia, cognitive decline, hypertension
The study is a two-arm, randomized controlled clinical trial using a prospective, open-label, blinded endpoint (PROBE) design. The study is conducted in China. Participants with newly diagnosed hypertension receive oral antihypertensive medication (AHM) in accordance with the national Chinese guidelines, which align with international recommendations for the management of primary hypertension. Randomization is performed centrally via the electronic CRF. Participants are randomized to four treatment groups (1:1:1:1), which differ in the sequence of second- and third-line therapy. For the primary analysis, these groups are combined into two treatment arms (ARB-based vs. ACEi-based). - Groups 1–2 (Intervention): Protocolized, stepped antihypertensive treatment initiated with an ARB, with dihydropyridine calcium channel blocker (diCCB) and thiazide allocated as second- and third-line therapy in alternate sequences. - Groups 3–4 (Comparator): Protocolized, stepped antihypertensive treatment initiated with an ACEi, with diCCB and thiazide allocated as second- and third-line therapy in alternate sequences. Since hyperuricemia (serum uric acid level >420 μmol/L or >7 mg/dL) is a contraindication for thiazides, individuals with these conditions follow an adapted treatment scheme. The same scheme is also provided to those with hypokalemia. For all groups, a beta-blocker may be added as fourth-line therapy if needed. Dosage modifications follow a predefined stepwise protocol to achieve blood pressure control (Systolic Blood Pressure (SBP) ≤ 140 mmHg and diastolic blood pressure (DBP) ≤ 90 mmHg). At treatment initiation and after each medication adjustment (dose change or addition), a 4-week follow-up is scheduled to assess blood pressure. Laboratory tests are performed as needed. If the blood pressure is adequately controlled and no safety concerns are identified, treatment is continued and reassessed after 6 months. If blood pressure remains controlled at that point
1. Individuals aged 65–80 years 2. Not currently on AHM 3. Willing to receive regular (ATC-listed) antihypertensive treatment 4. Current mean SBP ≥140 and/or DBP ≥90 mmHg 5. Who are either: 5.1. Newly diagnosed with primary hypertension 5.2. Previously diagnosed but never treated; or 5.3. Previously treated but stopped AHM >3 years before baseline
1. Current use of AHM 2. Dementia or relevant cognitive decline (defined as MMSE < 24 points; or < 21 points for ISCED level 1) 3. Contra-indications to use of an ARB or an ACEi