Optimal Antihypertensive Systolic Blood Pressure Targets

Hypertension – how low should we go and how should we get there?

Hypertension treatment is not as exciting as it used to be, but it is still one of the most important things that we can do to reduce cardiovascular disease (CVD) events and mortality. These two studies tell us about two important aspects of hypertension control: How low should we go? And how should we get there?

The first paper is a meta-analysis of seven hypertension trials involving 72,138 patients, which examined how low our target for hypertension should be. The authors compared a systolic blood pressure (SBP) of less than 130 mm Hg with 130 mm Hg. The occurrence of major CVD events was reduced by 22% (HR, 0.78; 95% CI, 0.70–0.87) in favor of SBP less than 130 mm Hg. All-cause mortality was also reduced by 11% (HR, 0.89; 95% CI, 0.79–0.99) in favor of SBP less than 130 mm Hg.

When the authors looked at an even lower SBP of less than 120 mm Hg compared with SBP of less than 140 mm Hg, there were only four studies that had that lower target of 120 mm Hg; hence, the number of participants and events was fewer. Despite that, major CVD events occurrence was reduced by 18% (HR, 0.82; 95% CI, 0.74–0.91) in favor of the group with a target SBP less than 120 mm Hg. The all-cause mortality was reduced by 15% but the upper limit crossed 1.00 (HR, 0.85; 95% CI, 0.71–1.01) and that might be due to the reduced numbers in this part of the analysis.

The side effects were slightly higher in the arms with more intensive treatments but the absolute numbers were very low. So, it is still worthwhile to go for the CVD and death reductions.

The conclusion was that there was clear CVD and mortality benefit of having SBP less than 130 mm Hg. In addition, there is CVD benefit for SBP less than 120 mm Hg with a trend to benefit for mortality as well.

The next question is how to get patients to these lower BP levels.

The second paper from our Nigerian colleagues used a triple pill combination to determine whether they could improve hypertension control. The authors looked at 300 patients with hypertension. Half of these patients had the usual titration method based on their current guidelines:

• amlodipine 5 mg
• amlodipine 5 mg + losartan 50 mg
• amlodipine 1 0mg + losartan 100 mg
• amlodipine 10 mg + losartan 100 mg + hydrochlorothiazide 25 mg
• referral to a specialist if target blood pressure is still not achieved

The other group had the triple combination pill. This is one pill with telmisartan, amlodipine, and indapamide. There are three strengths of this triple combination pill and each one has double the dose of all the components than the others. This was their titration strategy:

• telmisartan/amlodipine/indapamide - 10 mg /1.25 mg / 0.625 mg
• telmisartan/amlodipine/indapamide - 20 mg /2.50 mg / 1.250 mg
• telmisartan/amlodipine/indapamide - 40 mg /5.00 mg / 2.500 mg
• telmisartan/amlodipine/indapamide - 40 mg /5.00 mg / 2.500 mg + telmisartan/amlodipine 40mg / 5mg
• referral to a specialist if target blood pressure is still not achieved

At the 6-month mark, the blood pressure control was better in the triple pill arm than in the usual care arm. The home SBP for the usual care arm was reduced by 26 mm Hg (95% CI, 22–28 mm Hg). For the triple pill arm, the blood pressure was reduced by 31 mm Hg (95% CI, 28–33 mm Hg). That is a difference of −5.8 mm Hg (95% CI, −8.0 to −3.6; P < .001), which would most likely translate to reductions in the occurrence of CV events if this trial was continued for a longer duration.

Of note, 72% and 82% of patients in the usual titration and triple pill groups, respectively achieved target BP of 140/90 mm Hg. This 10% absolute difference would mean a reduction in CV event occurrence in a longer trial.

Only 28% in the usual titration group and 62% in the triple pill group achieved a home BP target of less than 130/80 mm Hg, translating to a 34% difference in the number of patients reaching the home BP target. This would translate into a very significant reduction in the rate CV event reductions if this was in a longer clinical trial.

The side effect profile was excellent because of the low doses in the triple therapy. Therefore, triple therapy is a very easy strategy to get more patients to achieve the target. Furthermore, in countries that have dispensing fees for each prescription, this triple pill would only have one dispensing fee as opposed to three. This could be a significant cost savings as well.

With these two excellent papers, we now know how low we should go and perhaps more importantly how we can get there easily and cheaply.

References

1. Whelton PK, O'Connell S, Mills KT, et al. Optimal Antihypertensive Systolic Blood Pressure: A Systematic Review and Meta-Analysis. Hypertension. 2024;81(11):2329-2339. https://doi.org/10.1161/hypertensionaha.124.23597
2. Ojji DB, Salam A, Sani MU, et al. Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria: A Randomized Clinical Trial. JAMA. 2024;332(13):1070-1079. https://doi.org/10.1001/jama.2024.18080