Hypotension during treatment with sacubitril/valsartan: practical tips for prevention and management

Prevention also includes patient awareness

In the PARADIGM-HF study, the use of sacubitril/valsartan was associated with a significantly lower risk of treatment discontinuation due to side effects than with enalapril. However, treatment with this angiotensin receptor and neprilysin inhibitor (ARNI) is not without risks. The most common symptomatic side effects of sacubitril/valsartan in the mentioned study were hypotension and orthostatic symptoms. Because these manifestations have potentially serious consequences (falls, fractures...), it is desirable to prevent them in the first place. Informing the patient about these risks and their cooperation can significantly help with this. Especially early on after starting or changing therapy, we can recommend the following to the patient:

• avoid dehydration
• carefully transition from lying or sitting to standing
• monitor their weight and blood pressure daily

The patient also needs to be informed about potentially serious symptoms and findings, such as dizziness, syncope, or systolic blood pressure < 90 mmHg. Although early checks (ideally after 14 days) are desirable after the initiation or dose increase of sacubitril/valsartan, the patient should have the possibility to contact their doctor sooner if symptoms occur and promptly consult further steps.

Consider reducing other antihypertensive medications

A suitable prevention of hypotension in patients taking diuretics, especially loop diuretics, can be reducing the dose or completely discontinuing them. It is also worth considering the preventive reduction of the dose or discontinuation of other medications with hypotensive effects that do not offer as great a benefit in terms of morbidity and mortality reduction – for example, calcium channel blockers.

Hypotension sometimes resolves quickly

If hypotension occurs during ARNI administration, it is advisable to first assess its symptomatic nature and the patient's overall condition – the clinical finding of hypotension is not always consistent with the patient's feeling about the therapy. Reducing the dose of sacubitril/valsartan, which is associated with a higher risk of cardiovascular death and hospitalizations for heart failure, can be avoided by reducing the dose of other medications or taking the medication before bedtime. Clinical practice shows that the side effect may also resolve within the first few weeks of therapy. In case of mild hypotension, it is sometimes possible to wait, along with thorough patient education on the measures and alarming symptoms mentioned above.

Downtitration is preferable to discontinuation

If the side effect persists, it is necessary to consider reducing the dose of sacubitril/valsartan. Again, the risks associated with complete discontinuation are significantly higher than with treatment, even at a lower drug dose.

Try increasing the dose again after resolution

1–2 weeks after the resolution of the side effect, an attempt should be made to increase the dose again. Many patients in the PARADIGM-HF study had successful 're-uptitration'.

Conclusion

Less severe side effects of treatment, such as hypotension, are generally well manageable and should not lead to fears of starting sacubitril/valsartan or to its hasty discontinuation. Similar is the case with hyperkalemia, whose incidence was also lower than with enalapril in the mentioned study and can be detected with appropriately timed laboratory tests (the ideal time is 3 days after starting the treatment when the drug level stabilizes in the body).

(luko)

Sources:
1. Sauer A. J., Cole R., Jensen B. C. et al. Practical guidance on the use of sacubitril/valsartan for heart failure. Heart Fail Rev 2019 Mar; 24 (2): 167−176, doi: 10.1007/s10741-018-9757-1.
2. SPC Entresto. Available at: www.ema.europa.eu/en/documents/product-information/entresto-epar-product-information_cs.pdf