New trials provide data to improve medication management in hypertension

Three recent studies looked at managing medications in patients with hypertension.

In the first study, a prospective, pragmatic, parallel-group trial in the United Kingdom, researchers tested whether evening or morning dosing of antihypertensive medications was related to major cardiovascular outcomes. Patients were randomly assigned to take all of their usual antihypertensive medications between 6 a.m. and 10 a.m. or between 8 p.m. and midnight. Vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke was the composite primary end point and was assessed as time to first occurrence in the intention-to-treat population. Participants who submitted at least one follow-up questionnaire were included in the safety analysis. The results were published Oct. 11 by The Lancet.

A total of 21,104 patients were randomly assigned between Dec. 17, 2011, and June 5, 2018, to evening (n=10,503) or morning (n=10,601) dosing. Mean age at study entry was 65.1 years, 57.5% of participants were men, 42.5% were women, and 13.0% had a previous cardiovascular disease. Almost all (90.5%) were White. Median follow-up was 5.2 years (interquartile range, 4.9 to 5.7 years). By the end of follow-up, 5.0% of those assigned to evening treatment and 3.0% of those assigned to morning treatment had completely withdrawn from the study. Overall, 3.4% of patients assigned to evening treatment and 3.7% assigned to morning treatment had a primary end point event (0.69 event [95% CI, 0.62 to 0.76 event] per 100 patient-years vs. 0.72 event [95% CI, 0.65 to 0.79] per 100 patient-years, respectively; unadjusted hazard ratio, 0.95 [95% CI, 0.83 to 1.10]; P=0.53). No safety concerns were noted.

The researchers pointed out that their pragmatic trial was open-label, among other limitations. “Taking medication in the evening was not harmful but provided no additional benefit versus morning dosing,” they wrote. “Therefore, patients should be advised that they need not change their antihypertensive medication dosing time but might choose to take their medication at a time that suits them best, because the timing makes no difference to cardiovascular outcomes.”

In the second study, published by Mayo Clinic Proceedings on Oct. 7, researchers looked at data from a U.S. national database to evaluate dosing of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in 100,238 adults with proteinuria, defined as a urine albumin-to-creatinine ratio of 30 mg/g or greater or a protein-to-creatinine ratio of 150 mg/g or greater. Guidelines for managing hypertension and chronic kidney disease (CKD) recommend titrating ACE inhibitors and ARBs to the maximum dose tolerated, the researchers said. Mean patient age was 65.1 years, 49.4% were women, 29.8% were taking maximal doses of ACE inhibitors and ARBs, and 8.4% had seen a nephrologist in the previous year.

Of the 74,287 patients who had no potential contraindications to dose escalation, defined as a systolic blood pressure below 120 mm Hg, an estimated glomerular filtration rate below 15 mL/min per 1.73 m², a serum potassium level greater than 5.0 mEq/L, or acute kidney injury within the previous year, 32.3% were taking maximal doses. Age younger than 40 years, female sex, Hispanic ethnicity, lower urine albumin-to-creatinine ratio, lack of diabetes, heart failure, lower blood pressure, higher serum potassium level, and previous acute kidney injury were associated with lower odds of maximal dosing in adjusted analyses. No association was seen between a previous nephrologist visit and maximal dosing.

The researchers noted that they defined proteinuria based on a single measurement and blood pressure as the median outpatient reading over the previous year, among other limitations. “Among adults with proteinuria prescribed ACEi [ACE inhibitors]/ARBs, a majority were taking submaximal doses, even among patients lacking apparent contraindications to ACEi/ARB up-titration,” the authors concluded. “Our results suggest that greater attention toward optimizing the dose of ACEi/ARB therapy may represent an opportunity to improve CKD care and reduce excess morbidity and mortality associated with CKD progression.”

Finally, a trial in Spain, published by the Journal of General Internal Medicine on Oct. 11, randomly assigned 312 adults with poorly controlled hypertension to usual care or blood pressure self-monitoring plus self-titration of antihypertensive medications based on an individualized plan developed with their physicians. At 12 months, the adjusted mean difference for the self-titration group versus the usual care group was −2.9 mm Hg (P=0.061) for systolic blood pressure and −1.9 mm Hg (P=0.052) for diastolic blood pressure, and more patients in the intervention group achieved blood pressure below 140/90 mm Hg. “Self-management of blood pressure including home blood pressure monitoring, educational components, and patients' self-titration of antihypertensive medication based on an individualized pre-arranged plan in the primary care setting may be a promising strategy for reducing blood pressure compared to usual care at 12 months of follow-up, without increasing healthcare utilization or adverse events,” the authors concluded.