Major CV Event Risk Reduced With Minimal Reduction in Systolic Blood Pressure

Woman using medical device to measure blood pressure
This study challenges the view that history of cardiovascular disease is a key factor in decisions about blood pressure-lowering treatment.

A reduction in systolic blood pressure of 5 mmHg can reduce a person’s risk for major cardiovascular events by roughly 10% regardless of previous diagnoses of cardiovascular disease (CVD) or blood pressure levels, according to research results published in Lancet.

This study, by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), includes the largest-ever collection of individual, participant-level data on blood pressure lowering trials, the study authors wrote. Using BPLTTC data, they conducted a participant-level meta-analysis of randomized clinical trials to investigate the effects of pharmacological blood pressure lowering therapies on major CV event risk in participants with and without CVD at baseline.

The current study included BPLTTC trials that collected and shared information on baseline participant blood pressure, primary and secondary outcomes including event timing, and the presence or absence of previous CVD at baseline. The primary outcome was major CV events — defined as a composite of fatal or nonfatal stroke, fatal or nonfatal myocardial infarction or ischemic heart disease, or heart failure causing death or hospital admission. Secondary outcomes included all-cause death and death due to CVD.

In total, 51 randomized trials were identified by the BPLTTC; all but 3 were included in the study, and data for 4138 participants with a known heart failure diagnosis at baseline were excluded. The total cohort, then, included data for 344,716 participants (mean age at baseline, 65 years) across 48 trials.

Thirty-seven of the trials included participants with and without baseline CVD; 10 trials were restricted to include participants with CVD only at baseline, and 1 trial was conducted exclusively in participants without baseline CVD.

Within the trials, the proportion of women without previous CVD was higher than the proportion of women with previous CVD at baseline. While the prevalence of atrial fibrillation and diabetes was similar in patients with vs without previous CVD, peripheral vascular disease was more common in patients with previous CVD.

Median follow-up was 4.15 years. At the end of this follow-up period, 12.3% of participants experienced at least 1 major CV event, including 4% with stroke, 5.6% with ischemic heart disease, and 2.4% with heart failure. Of the 8.4% of participants who died, 3.4% of deaths were due to CVD.

Within the group of participants who did not have CVD at baseline, the incidence rate for developing major CV events per 1000 person-years was 31.9 (95% CI, 31.3-32.5) in the comparator group vs 25.9 (95% CI, 25.4-26.4) in the intervention group. Among participants with previous CVD at baseline, corresponding rates were 39.7 and 36, respectively (95% CI, 39.0-40.5 and 35.3-36.7, respectively).

Hazard ratios (HRs) associated with reduced systolic blood pressure by 5 mmHg for major CV events at the end of the follow-up period were 0.89 in those with previous CVD and 0.91 in those without previous CVD (95% CI, 0.86-0.92 and 0.89-0.94, respectively).

No observable difference in patterns of events occurring over time for secondary vs primary outcomes between participants with vs without previous CVD was noted.

Results of a meta-regression analysis indicated that HRs for major CV events were proportional to the magnitude of the systolic blood pressure reduction achieved at the trial level. A reduction of 5 mmHg reduced major CV event risk, regardless of CVD stratification, and no evidence of clinically meaningful heterogenous treatment effects between groups was noted.

When analyses were repeated in groups stratified by baseline CVD status and blood pressure categories unstandardized for blood pressure reductions, findings were “broadly similar to the overall analysis,” with no substantial difference in results after excluding drug class comparison trials. Findings based on absolute risk reduction confirmed that there is no observable heterogeneity of effect by baseline CVD status and systolic blood pressure category.

Limitations include the likely underrepresentation of some groups of patients, which limits generalizability; no the lack of investigation of potential treatment harms; and the investigators’ limited definition of major CV events, which did not include outcomes such as valvular heart disease, peripheral vascular disease, atrial fibrillation, or diabetes.

“This study provides evidence against the widely held view that an individual’s blood pressure or previous diagnosis of cardiovascular disease per se are key factors for selecting or deselecting participants for blood pressure-lowering treatment,” the researchers concluded.

“These findings call for revision of clinical guideline recommendations globally and suggest that antihypertensive medications are better viewed as treatment options for prevention of cardiovascular disease, regardless of an individual’s blood pressure level and their previous history of cardiovascular disease.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Blood Pressure Lowering Treatment Trialists’ Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. Published online May 1, 2021.doi:10.1016/S0140-6736(21)00590-0