Aliskiren not recommended as first-line therapy for hypertension

The direct renin inhibitor aliskiren offers limited benefits in patients with hypertension, helping control blood pressure (BP) but neither preventing major adverse cardiovascular outcomes nor reducing total mortality, according to the results of a systematic review and meta-analysis.

“Thus, this review does not recommend aliskiren as first-line treatment for hypertension,” the investigators said.

The meta-analysis included 37 randomized controlled trials of BP-lowering treatment with aliskiren, corresponding to a population of 35,916 adult patients with essential hypertension, heart failure, myocardial infarction or diabetes. The drug was given at 75-, 150-, 300- or 600-mg doses, with treatment lasting at least 4 weeks.

Pooled data showed that compared with other antihypertensive agents, aliskiren conferred slightly greater effects on systolic and diastolic BP (weighted mean difference [WMD], −1.14 mm Hg, 95 percent confidence interval [CI], −2.78 to 0.50 and WMD, −0.77 mm Hg, 95 percent CI, −2.01 to 0.46, respectively). Comparator drugs used were ramipril, valsartan, irbesartan, hydrochlorothiazide and atenolol. [J Hum Hypertens 2019;33:795-806]

When used as an add-on drug to antihypertensive therapy, aliskiren yielded further reductions in BP (WMD for SBP, −5.07 mm Hg, 95 percent CI, −6.08 to −4.06; WMD for DBP, −2.74 mm Hg, 95 percent CI, −3.39 to −2.09) but did not modify the risk of the following outcomes: total mortality (weighted relative risk [WRR], 0.99, 95 percent CI, 0.87−1.11), cardiovascular (CV) death (WRR, 0.99, 95 percent CI, 0.86−1.14), myocardial infarction (WRR, 0.85, 95 percent CI, 0.60−1.23) or stroke (WRR, 0.96, 95 percent CI, 0.71−1.29).

Furthermore, in diabetic patients, add-on aliskiren had the potential to contribute to an increase in total mortality (WRR, 1.06, 95 percent CI, 0.88–1.28) and cardiovascular death (WRR, 1.09, 95 percent CI, 0.94–1.24).

The incidence of adverse effects was similar in the aliskiren and placebo groups (WRR, 0.99, 95 percent CI, 0.90–1.09). The study drug was associated with fewer cases of coughing as compared with ACE inhibitors (WRR, 0.51, 95 percent CI, 0.27–0.96), as well as with similar risk of hyperkalaemia when compared with other renin–angiotensin–aldosterone system (RAAS) inhibitors (WRR, 1.20, 95 percent CI, 0.72–2.01).

“Aliskiren is generally well tolerated and can be safely administered as monotherapy or in combination with other drugs if other first-line treatments are unsuccessful or cause unacceptable adverse effects,” the investigators said.

“This review supports the current recommendations stating that aliskiren and ACE inhibitor combination is contraindicated in diabetes patients. Efficacy and safety of aliskiren monotherapy in diabetic patients remains to be investigated,” they added. [Eur Heart J 2013;34:2159-2219]

Additional trials evaluating aliskiren against other RAAS-inhibiting agents, each of which in combination with another first-line antihypertensive drug (eg, a diuretic or calcium channel antagonist), are warranted.