What is the clinical evidence from this study?

Study design: RCT. Population: Hypertension (n=1250). Intervention: Aliskiren vs. Irbesartan 300 mg and ramipril 10 mg. Primary outcome: Predicted rise in SBP when reducing adherence from 90% to 60%.

What does this research mean for the field?

Aliskiren, an antihypertensive with a prolonged duration of action, results in a smaller predicted rise in systolic blood pressure and fewer additional cardiovascular events compared to irbesartan and ramipril when patient adherence is reduced. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 6, 2011

Impact of prolonged antihypertensive duration of action on predicted clinical outcomes in imperfectly adherent patients: comparison of aliskiren, irbesartan and ramipril

Key Result

Aliskiren resulted in a smaller predicted rise in systolic blood pressure (1.0 vs 2.5 and 2.2 mmHg) and fewer additional CVD events (3 vs 7.5 and 6.7 per 1000) when adherence was reduced to 60%.

Study Design

Type

RCT (n=1,250)

Blinding

Double-blind

Structured PICO

Does the use of antihypertensive drugs with a longer duration of action (aliskiren) improve predicted SBP reduction and CVD risk compared to irbesartan or ramipril in imperfectly adherent patients?

Population

1,250 simulated patients with hypertension and a baseline 10-year CVD risk of 27%, modeled over 256 days.

Intervention

Aliskiren 300 mg (simulated 256-day dosing history with varying adherence levels)

Comparator

Irbesartan 300 mg and ramipril 10 mg (simulated 256-day dosing histories with varying adherence levels)

Outcome

Estimated mean reductions in systolic blood pressure (SBP) and 10-year cardiovascular disease (CVD) risksurrogate

Antihypertensive drugs with a longer duration of action, such as aliskiren, may provide more consistent blood pressure control and lower predicted CVD risk in patients with imperfect adherence compared to irbesartan or ramipril.

Main Result

Absolute Event Rate: 1% vs 2.5%

Abstract

BACKGROUND: Most patients miss occasional doses of antihypertensives. The use of 'forgiving' drugs (i.e. drugs with duration of action longer than the 24-h dosing interval) may allow an adequate blood pressure (BP) reduction to be maintained despite missed doses. AIM: To quantify the effects of adherence level and duration of action on estimated mean systolic BP (SBP) reduction and cardiovascular disease (CVD) risk. METHOD: For 1250 patients, we simulated 256-day dosing histories with realistically distributed drug holidays based on a study of electronically monitored dosing records. Adherence was set to the desired level by altering the proportion of doses missed. Mean office SBP-lowering effect (aliskiren 300 mg, -14.1 mmHg; irbesartan 300 mg, -13.3; ramipril 10 mg, -10.1 mmHg) and the rate of SBP increase after stopping treatment (off-rate; aliskiren, 1.0 mmHg/day; irbesartan, 3.6 mmHg/day; ramipril, 4.0 mmHg/day) were taken from the results of a randomised, double-blind trial. SBP was averaged over time and patient to estimate mean reductions in SBP and 10-year CVD risk (Framingham risk equation, baseline absolute 10-year CVD risk: 27%). RESULTS: Predicted reductions in SBP and CVD risk with aliskiren were larger and less affected by imperfect adherence than the reductions with irbesartan or ramipril. For aliskiren, reducing adherence from 90% to 60% led to a predicted rise in SBP of 1.0 mmHg and three additional CVD events per 1000 treated patients; larger predicted differences were observed for irbesartan (2.5 mmHg; 7.5 events/1000 treated patients) and ramipril (2.2 mmHg; 6.7 events/1000 treated patients). CONCLUSION: To offset the effects of imperfect adherence, a common challenge with antihypertensives, for better BP management it may be prudent to prescribe 'forgiving' drugs.

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