Luis Carlos Saiz, Javier Gorricho, Javier Garjón, Mª Concepción Celaya, Lourdes Muruzábal, Mª del Mar Malón, Rodolfo Montoya, Antonio López

Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. To determine if 'lower' blood pressure targets (≤ 135/85 mmHg) are associated with reduction in mortality and morbidity as compared with 'standard' blood pressure targets (≤ 140 to 160/ 90 to 100 mmHg) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the Latin American and Caribbean Health Science Literature Database (from 1982) and contacted authors of relevant papers regarding further published and unpublished work. There were no language restrictions. We included randomized controlled trials (RCTs) with more than 50 participants per group and at least six months follow-up. Trial reports needed to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions were lower target for systolic/diastolic blood pressure (≤ 135/85 mmHg) compared with standard target for blood pressure (≤ 140 to 160/90 to 100 mmHg).Participants were adults with documented hypertension or who were receiving treatment for hypertension and cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease or angina pectoris. Two review authors independently assessed search results and extracted data using standard methodological procedures expected by The Cochrane Collaboration. We included six RCTs that involved a total of 9795 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). Five RCTs provided individual patient data for 6775 participants.We found no change in total mortality (RR 1.05, 95% CI 0.90 to 1.22) or cardiovascular mortality (RR 0.96, 95% CI 0.77 to 1.21; moderate-quality evidence). Similarly, no differences were found in serious adverse events (RR 1.02, 95% CI 0.95 to 1.11; low-quality evidence). There was a reduction in fatal and non fatal cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization or death from congestive heart failure) with the lower target (RR 0.87, 95% CI 0.78 to 0.98; ARR 1.6% over 3.7 years; low-quality evidence). There were more participant withdrawals due to adverse effects in the lower target arm (RR 8.16, 95% CI 2.06 to 32.28; very low-quality evidence). Blood pressures were lower in the lower' target group by 9.5/4.9 mmHg. More drugs were needed in the lower target group but blood pressure targets were achieved more frequently in the standard target group. No evidence of a difference in total mortality and serious adverse events was found between treating to a lower or to a standard blood pressure target in people with hypertension and cardiovascular disease. This suggests no net health benefit from a lower systolic blood pressure target despite the small absolute reduction in total cardiovascular serious adverse events. There was very limited evidence on adverse events, which lead to high uncertainty. At present there is insufficient evidence to justify lower blood pressure targets (≤ 135/85 mmHg) in people with hypertension and established cardiovascular disease. More trials are needed to answer this question.