Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/ valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction

Results fromPARADIGM-HF

Michael Böhm, Robin Young, Pardeep S. Jhund, Scott D. Solomon, Jianjian Gong, Martin P. Lefkowitz, Adel R. Rizkala, Jean L. Rouleau, Victor C. Shi, Karl Swedberg, Michael R. Zile, Milton Packer, John J.V. McMurray

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP. Methods We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP. Findings All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a Ushaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP <110mmHg and 0.81 (0.65-1.02) for those with a SBP ≥140mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP. Interpretation In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP.

Original languageEnglish (US)
Pages (from-to)1132-1143
Number of pages12
JournalEuropean Heart Journal
Volume38
Issue number15
DOIs
StatePublished - Apr 14 2017

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Heart Failure
Blood Pressure
Safety
Enalapril
LCZ 696
Hypotension
Hospitalization
Neprilysin
Angiotensin Receptors

Keywords

  • Angiotensin
  • AT1-receptor
  • Blood pressure
  • Heart failure
  • Neprilysin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/ valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction : Results fromPARADIGM-HF. / Böhm, Michael; Young, Robin; Jhund, Pardeep S.; Solomon, Scott D.; Gong, Jianjian; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Swedberg, Karl; Zile, Michael R.; Packer, Milton; McMurray, John J.V.

In: European Heart Journal, Vol. 38, No. 15, 14.04.2017, p. 1132-1143.

Research output: Contribution to journalArticle

Böhm, M, Young, R, Jhund, PS, Solomon, SD, Gong, J, Lefkowitz, MP, Rizkala, AR, Rouleau, JL, Shi, VC, Swedberg, K, Zile, MR, Packer, M & McMurray, JJV 2017, 'Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/ valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction: Results fromPARADIGM-HF', European Heart Journal, vol. 38, no. 15, pp. 1132-1143. https://doi.org/10.1093/eurheartj/ehw570
Böhm, Michael ; Young, Robin ; Jhund, Pardeep S. ; Solomon, Scott D. ; Gong, Jianjian ; Lefkowitz, Martin P. ; Rizkala, Adel R. ; Rouleau, Jean L. ; Shi, Victor C. ; Swedberg, Karl ; Zile, Michael R. ; Packer, Milton ; McMurray, John J.V. / Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/ valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction : Results fromPARADIGM-HF. In: European Heart Journal. 2017 ; Vol. 38, No. 15. pp. 1132-1143.
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N2 - Background Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP. Methods We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP. Findings All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a Ushaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP <110mmHg and 0.81 (0.65-1.02) for those with a SBP ≥140mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP. Interpretation In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP.

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