Cardiovascular (CV) outcomes are more accurately predicted by visit-to-visit systolic blood pressure variation (SBPV) in hypertensive and normotensive patients. Compared with atenolol-based therapy, amlodipine-based therapy offers long-term benefits in multiple CV outcomes. these are, european heart journal.

The researchers investigated the effects of mean blood pressure and SBPV during the trial on long-term CV outcomes, and the effects of either of the two blood pressure-lowering regimens assigned during the trial on long-term non-fatal or fatal CV events. The aim was to characterize whether the

Researchers conducted an observational cohort study (ASCOT Legacy Cohort), a long-term follow-up of participants in the ASCOT trial. Briefly, the ASCOT trial enrolled 19,257 hypertensive women and men between the ages of 40 and 79 with at least three additional cardiovascular disease risk factors. Patients were randomly assigned to receive amlodipine and as needed perindopril (amlodipine-based) or atenolol and as needed bendroflumethiazide (atenolol-based). Among patients recruited from the Nordic countries, the United Kingdom, and Ireland between February 1998 and May 2000, the main outcomes were nonfatal myocardial infarction and fatal coronary heart disease.

The Data Safety Monitoring Board recommended discontinuing atenolol-based therapy in December 2004 because mortality was significantly higher in patients assigned to atenolol-based therapy versus those receiving amlodipine-based therapy.

In the current ASCOT legacy cohort, it is not possible to use electronic records for participants recruited in the Nordic countries and these participants were dismissed, leaving 8580 participants from England and Wales (allocated to amlodipine-based 4,305 patients assigned to atenolol-based therapy and 4,275 patients assigned to atenolol-based therapy remained. , or Scotland followed until completion of atenolol-based treatment (717 participants died). The remaining participants who consented (n=7092) were followed up (median 17) [IQR, 9-19] until January 2019 in case of death or hospitalization).

At ASCOT Legacy entry, participants had a mean age of 64.2 (SD, 8.1) years, 18.9% female, 89.7% Caucasian, and mean SBP 161.6 to 162.1 mm Hg. Researchers noted that 91.8% of patients were taking antihypertensive medications.

The difference in mean SBP during the study was small (amlodipine-based, 136.3 [SD, 9.9] mmHg vs atenolol-based, 138.0 [SD, 10.0] mmHg). On-study differences in SBPV between visits were greater (amlodipine-based, 10.8) [SD, 4.4] vs atenolol-based, 12.8 [SD, 4.8]; all P <.001).

Researchers found that SBP was a predictor of CV outcome (hazard ratio). [HR] per 10 mm Hg, 1.14; 95% CI, 1.10-1.17), but SBPV independent of mean SBP was a strong predictor of CV events (HR per 5 mm Hg, 1.22; 95% CI, 1.18 -1.26, all) P <.001), including prediction of events among participants whose blood pressure was well controlled.

During long-term follow-up, researchers noted that CV events were significantly reduced in participants who received amlodipine-based treatment versus those who received atenolol-based treatment (HR, 0.93; 95% CI, 0.88-0.98; 95% CI, 0.88-0.98; P =.008), total coronary events (HR, 0.92; 95% CI, 0.86-0.99; P =.024), atrial fibrillation (HR, 0.91; 95% CI, 0.83-0.99; P =.030), stroke risk (HR, 0.82; 95% CI, 0.72-0.93; P =.003). No significant difference in CV mortality was observed (HR, 0.91; 95% CI, 0.82-1.01; 95% CI, 0.82-1.01; P =.073).

The researchers found no significant differences between treatment groups in rates of all-cause mortality, heart failure, fatal coronary heart disease, or nonfatal myocardial infarction.

Study limitations include limited blood pressure measurement and blood pressure treatment data from the posttrial substudy sample and the use of ICD-10 codes as a proxy for nonfatal outcomes.

“Our study…shows that visit-to-visit BPV is a much stronger determinant of CV outcome, and that at least half of all CV events in our cohort occur when blood pressure is controlled but BPV is high. “We provide strong evidence that this occurred in humans,” the researchers wrote. “The long-term benefit of amlodipine-based therapy compared with atenolol-based therapy in reducing CV events appears to be primarily mediated by its effect on systolic BPV during the study period.”

Disclosure: This study (original ASCOT study) was supported by: Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original bibliography for a complete list of author disclosures.