Mean follow-up of 1.6–12.2 years Average 7.5/4.5 mmHg BP reduction vs. less intensive treatment 11 % RR reduction for major CV events, 13 % for MI, 24 % for stroke, 11 % for end-stage kidney disease HOPE [19] 9,297 high-risk patients (aged ≥55 years, with vascular disease or diabetes mellitus, plus one other CV risk factor) Composite of MI, stroke, or death from CV causes. Mean follow-up of 5 years Composite endpoint reached by 14 % of treated patients vs. 17.8 % of those on placebo Treatment reduced rates of MI (RR: 0.80), stroke (RR: 0.68), all-cause mortality (RR:

0.84), cardiac arrest (RR: 0.63), and complications of diabetes (RR: 0.84) PROGRESS [20] 6,105 patients with VS-4718 cerebrovascular disease Incidence of total stroke Similar risk reduction regardless

of baseline BP Lowest risk of stroke recurrence in patients with lowest follow-up BP (112/72 mmHg), rising progressively with BP ACCORD [22] 4,733 patients with type 2 diabetes Composite of non-fatal MI, non-fatal stroke, or death from CV causes. Mean follow-up of 4.7 years Annual rate of primary outcome was 1.87 % with intensive therapy and 2.09 % with standard therapy (HR with intensive therapy: 0.88; https://www.selleckchem.com/autophagy.html 95 % CI 0.73, 1.06; p = 0.20) Annual rate of stroke (secondary outcome) significantly lower in the intensive treatment arm (0.32 vs. 0.53 %; HR: 0.59; 95 % CI 0.39, 0.89; p = 0.01) VALUE [17] 15,245 patients aged ≥50 years with treated or untreated hypertension and high risk of cardiac events Composite of cardiac mortality and morbidity. Mean follow-up of 4.2 years Earlier BP reductions were associated with fewer patients reaching the composite endpoint Patients achieving SBP <140 mmHg at 6 months had a reduced HR for cardiac events, stroke, all-cause mortality, and heart failure hospitalizations HOT [21] 18,790 patients aged 50–80 years with hypertension and DBP of 100–115 mmHg Incidence of CV events in subgroups of patients with target DBP of ≤90, ≤85, and ≤80 mmHg Lowest incidence of CV events occurred

at mean DBP of 82.6 mmHg Lowest risk of CV mortality occurred Loperamide at 86.5 mmHg In patients with diabetes, DBP ≤80 mmHg was associated with a 51 % reduction in CV events vs. DBP ≤90 mmHg ACCORD Action to Control Cardiovascular Risk in Diabetes, BP blood pressure, CCB calcium channel blocker, CHD coronary heart disease, CI confidence interval, CV cardiovascular, DBP diastolic blood pressure, HOPE Heart Outcomes Prevention Evaluation, HOT Hypertension Optimal Treatment, HR hazard ratio, MI myocardial infarction, PROGRESS Perindopril pROtection aGainst REcurrent Stroke Study, RR relative risk, SBP systolic blood pressure, VALUE Valsartan Antihypertensive Long-term Use Evaluation Fig. 1 Effect of intensive BP lowering on risk of CV outcomes: a major CV events, b MI, c stroke, and d CV mortality.