Enfermedad caracterizada aumento de presión arterial persistente en arterias sistémicas. Guias Clinicas (ESC 2013/JNC 7):

PA alta Hipertension Arterial

∆ in home SBP between spironolactone and placebo: mm Hg (p < 0.001) ∆ in home SBP between spironolactone and bisoprolol/doxazosin (groups combined): mm Hg (p < 0.001) ∆ in home SBP between spironolactone and doxazosin: mm Hg (p < 0.001) ∆ in home SBP between spironolactone and bisoprolol: mm Hg (p < 0.001) Trial design: Patients with resistant hypertension were randomized to each of four different add-on study medications, each for a 12-week period; spironolactone mg daily, doxazosin 4-8 mg daily, bisoprolol 5-10 mg daily, or placebo. Results Conclusions Among patients with resistant hypertension, spironolactone was the most effective add-on agent for improved blood pressure control Spironolactone improved SBP nearly 9 mm Hg vs. placebo and approximately 4 mm reduction vs. active anti-hypertensive agents Williams B, et al. Lancet 2015;Sep 21:[Epub] p < for each group Spironolactone vs. placebo Spironolactone vs. bisoprolol/doxazosin Spironolactone vs. doxazosin Spironolactone vs. bisoprolol mm Hg

One Enzyme — Neprilysin — Degrades Many Endogenous Vasoactive Peptides Endogenous vasoactive peptides (natriuretic peptides, adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) Neprilysin

Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter Maladaptive Mechanisms in Heart Failure Endogenous vasoactive peptides (natriuretic peptides, adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) Neprilysin Neprilysininhibition

Myocardial or vascular stress or injury Evolution and progression of heart failure Mechanisms of Progression in Heart Failure Angiotensin receptor blocker Angiotensin receptor blocker Inhibition of neprilysin Increased activity or response to maladaptive mechanisms Decreased activity or response to adaptive mechanisms

LEADER trial: Primary Outcome Placebo Liraglutide Patients with an event (%) Months since randomisation Hazard ratio, 0.87 (95% CI, 0.78–0.97) P<0.001 for noninferiority P=0.01 for superiority First occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke in the time-to- event analysis in patients with type 2 diabetes and high CV risk. Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial Adapted from: Marso SP et al., NEJM 2016

Hazard ratio (95% CI)P value Primary composite endpoint*0.86 ( )0.04 Secondary composite endpoint † 0.89 ( )0.08 Death from any cause0.68 ( )<0.001 CV death0.62 ( )<0.001 Fatal or nonfatal MI0.87 ( )0.23 Hospitalization for HF0.65 ( )0.002 Hospitalization for HF or CV death0.66 ( )<0.001 Clinical Outcomes with Empagliflozin 26 EMPA-REG OUTCOME Pooled Analysis (N=7020) *CV death, nonfatal MI (excluding silent MI), or nonfatal stroke; † CV death, nonfatal MI (excluding silent MI), nonfatal stroke, and hospitalization for unstable angina. CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; MI, myocardial infarction. Zinman B, et al. N Engl J Med. 2015;373: Favors empagliflozin

Hazard ratio (95% CI)P value Incident or worsening nephropathy or CV death 0.61 ( )<0.001 Incident or worsening nephropathy0.61 ( )<0.001 Progression to macroalbuminuria0.62 ( )<0.001 Doubling of SCr + eGFR ≤ ( )<0.001 Initiation of renal replacement therapy0.45 ( )0.04 Doubling of SCr + eGFR ≤45, renal replacement therapy, or renal disease death 0.54 ( )<0.001 Incident albuminuria*0.95 ( )0.25 Renal Outcomes with Empagliflozin Over 3.2 Years 27 EMPA-REG RENAL (N=7020) *In patients with normal albuminuria at baseline. CI, confidence interval; CV, cardiovascular; eGFR, estimated glomerular filtration rate in mL/min/1.73 m 2 ; HR, hazard ratio; SCr, serum creatinine. Wanner C, et al. N Engl J Med Jun 14. [Epub ahead of print] Favors empagliflozin

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