NEW YORK (Reuters Health) – A low-dose fixed-dose combination of three antihypertensive drugs improves blood pressure control but is associated with greater rates of therapeutic inertia, compared with usual care, according to a secondary analysis of the TRIUMPH trial.
“Initial or early low-dose combination therapy can achieve hypertension control rates of around 70%, but if we want to achieve even better results, then additional up titrations are needed,” Dr. Anthony Rodgers of The George Institute for Global Health, University of New South Wales, in Camperdown, Australia, told Reuters Health by email.
Major barriers to blood pressure control include inaccessibility to healthcare, poor medication adherence, and failure to intensify treatment despite poor blood pressure control (i.e., therapeutic inertia). The use of fixed-dose combinations (FDCs) aims to address these potential barriers, but there are limited data on the association of FDCs with therapeutic inertia.
Dr. Rodgers and colleagues investigated the association of antihypertensive triple-drug FDC therapy with therapeutic inertia and prescribing patterns in their post hoc analysis of the TRIUMPH trial of patients with persistent mild to moderate hypertension.
In that trial, 349 patients were randomized to a once-daily FDC pill of three antihypertensives at half the standard doses (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg), and 351 patients were assigned to usual care (where investigators were asked to follow their local guidelines to achieve blood pressure targets without any restrictions). In the FDC group, a higher-dose version of the triple pill was available for treatment intensification at the discretion of the treating physician.
Significantly more patients in the FDC group than in the usual-care group achieved blood pressure targets at week 6 (67.8% vs. 43.6%) and week 12 (72.6% vs. 47.4%), the researchers report in JAMA Cardiology.
When the study ended after six months, 69.5% of patients in the FDC group had reached their blood pressure targets, compared with 55.3% of patients getting usual care.
“Low-dose triple therapy reduced the overall number of treatment-inertia episodes, since there were fewer people who needed treatment intensification in the low-dose triple group,” Dr. Rodgers said.
But among patients who did not reach targets, the rate of therapeutic inertia was significantly higher in the FDC group at week 6 (86.8% vs. 63.9%) and at week 12 (90% vs. 64.8%).
At six months, the most commonly prescribed treatment regimen in the FDC group was the triple pill with no additional therapy (84.4% of patients), whereas monotherapy with an angiotensin-receptor blocker was the most commonly prescribed treatment regimen in the usual-care group (46.0%).
Only 2.9% of patients in the FDC group received the full-dose triple pill at the six-month follow-up.
Patients in the FDC group received far fewer changes in treatment regimen and were taking more classes of blood pressure-lowering drugs from six weeks onwards.
A greater proportion of patients in the FDC group had blood pressure levels more than 10 mmHg below the blood pressure target and fewer were more than 10 mmHg above their blood pressure targets at both week 6 and week 12.
Randomization to the FDC group was associated with 50% higher odds of reaching the blood pressure target at the end of the study, and failure to intensify treatment (regardless of group) was strongly associated with failure to reach blood pressure targets at the end of the study.
“We need to continue to address treatment inertia, which is a major barrier to better hypertension control rates, and focus on this issue among the minority of patients not controlled with combination therapy,” Dr. Rodgers said. “This is particularly important since hypertension guidelines are increasingly recommending initial combination therapy for many if not most patients.”
Coauthor Dr. Nelson Wang, also at The George Institute for Global Health, told Reuters Health by email, “Clinicians should use combination antihypertensive therapies as first line in the treatment of hypertension, as it achieves greater rates of blood pressure control and also reduces the opportunities for subsequent therapeutic inertia.”
Dr. Ann Marie Navar of Duke Clinical Research Institute, in Durham, North Carolina, who is associate editor of JAMA Cardiology and coauthored an accompanying editorial, told Reuters Health by email, “I was pleasantly surprised to see the authors take on this analysis – rather than just stop at seeing the efficacy of fixed dose combination therapy in the primary analysis, they went beyond to look for potential downsides of FDC therapy. And in spite of higher relative rates of therapeutic inertia in the FDC arm, they still saw benefit. You can imagine that the benefit of FDC would have been even higher if therapeutic inertia had not been increased.”
“As clinicians, we have to be vigilant to follow up responses and up-titrate if not at goal,” she said. “Here is where systems of care can be helpful – the more we can automate this titration and follow-up plan, the less we’ll be at risk for clinician-induced therapeutic inertia.”
Dr. Navar added, “Hypertension is not horseshoes: close is not good enough, and you get as many tries as you need. Don’t forget to bring your patients back, assess response, and be ready to make changes.”
Dr. Stefan Farsky, chairman of the Slovak League against Hypertension, in Martin, Slovakia, who recently analyzed therapeutic effectiveness and therapeutic inertia in hypertensive patients with metabolic syndrome and/or type 2 diabetes, told Reuters Health by email that expressing therapeutic inertia as either yes or no doesn’t tell the full story.
Experienced clinicians might tolerate blood pressures slightly above target levels, especially with older patients and when home blood pressure values are lower than those seen in the clinic, said Dr. Farsky, who was not involved in the new analysis.
SOURCE: https://bit.ly/3jUWOUy and https://bit.ly/3fiFAwG JAMA Cardiology, online July 22, 2020.