- BACKGROUND: Hypertension guidelines advise aggressive blood pressure (BP) lowering in patients with diabetes or high cardiovascular risk, but supporting evidence is limited. We analysed the impact of BP on cardiovascular events in well treated high-risk patients enrolled in a large clinical trial (Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). METHODS: Twenty-five thousand five hundred and eighty-eight patients with atherosclerotic disease or diabetes with organ damage, tolerant to angiotensin-converting enzyme inhibitors, were randomized to ramipril, telmisartan or both. We related the primary composite outcome and its components to: baseline SBP; SBP changes from baseline to event; and average in-trial SBP. RESULTS: The risk of myocardial infarction did not increase with baseline SBP and was unaffected by subsequent SBP change. In contrast, stroke risk progressively increased with baseline SBP (P for trend <0.0001) and decreased with reduction. In patients with baseline SBP less than 130 mmHg, adjusted for several covariates, cardiovascular mortality increased with further SBP reduction (P < 0.0001). A J-curve (nadir around 130 mmHg) occurred in the relationship between in-treatment SBP and all outcomes except stroke. CONCLUSION: In high-risk patients, the benefits from SBP lowering below 130 mmHg are driven mostly by a reduction of stroke; myocardial infarction is unaffected and cardiovascular mortality is unchanged or increased. Future trials should be designed to test the value of SBP lowering in high-risk patients with SBP in the range of 130-150 mmHg.