New and emerging cardiovascular and antihypertensive drugs

References

• Fryar CD, Ostchega Y, Hales CM, et al. Hypertension prevalence and control among adults: United States. 2015-2016. CDC, NCHS data brief 289 October 2017.
   Google Scholar
• Muntner P, Carey RM, Gidding S, et al. Potential U.S. population impact of the 2017 ACC/AHA high blood pressure guideline. J Am Coll Cardiol. 2018;71:109–1018.
   PubMed Web of Science ®Google Scholar
• GBD 2015. Risk factors collaborators. global, regional, and national comparative risk assessment of 79 behavioral, environmental, and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388L:1659–1724.
   Google Scholar
• Chobanian AV, Bakris GL, Blach HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–1252.
   PubMed Web of Science ®Google Scholar
• Azizi M, Rossignol P, Hulot JS. Emerging drug classes and their potential use in hypertension. Hypertension. 2019;74:1075–1083.
   PubMed Web of Science ®Google Scholar
• Chrysant SG, Miller E. Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients. Clin Cardiol. 1994;17:670–674.
   PubMed Web of Science ®Google Scholar
• Chrysant SG. The role of angiotensin receptor blocker and calcium channel blocker combination therapy in treating hypertension: focus on recent studies. Am J Cardiovasc Drugs. 2010;10:315–320.
   PubMed Web of Science ®Google Scholar
• Chrysant SG, Murray AV, Hoppe UC, et al. Long-term safety and efficacy of aliskiren and valsartan combination with and without the addition of HCT in patients with hypertension. Curr Med Res Opin. 2010;26:2841–2849.
   PubMed Web of Science ®Google Scholar
• Chrysant SG, Izo JL, Kereiakes DJ, et al. Efficacy and safety of triple-combination therapy with olmesartan, amlodipine, and hydrochlorothiazide in study participants with hypertension and diabetes: a subpopulation analysis of the TRNITY study. J Am Soc Hypertens. 2012;6:132–141.
   PubMed Web of Science ®Google Scholar
• Burnet JC Jr. Vasopeptidase inhibition: a new concept in blood pressure management. J Hypertens (Suppl). 1999;17:S37–S43.
   Google Scholar
• Kostis JB, Packer M, Black HR, et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs Enalapril (OCTAVE) trial. Am J Hypertens. 2004;17:103–111.
   PubMed Web of Science ®Google Scholar
• Nussberger J, Cugno M, Amstutz C, et al. Plasma bradykinin in angioedema. Lancet. 1998;351:1693–1697.
   PubMed Web of Science ®Google Scholar
• McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.
   PubMed Web of Science ®Google Scholar
• Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomized controlled trial. Lancet. 2012;380:1387–1395.
   PubMed Web of Science ®Google Scholar
• Solomon SD, McMurray JJV, Anand J, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609–1620.
   PubMed Web of Science ®Google Scholar
• Chrysant SG. LCZ696, Angiotensin AT1 receptor blocker/neprilysin inhibitor for the treatment of heart failure and hypertension. Drugs Future. 2011;36:183–190.
   Web of Science ®Google Scholar
• Chrysant SG. Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ696: sacubitril/valsartan. J Am Soc Hypertens. 2017;11:461–468.
   PubMed Web of Science ®Google Scholar
• Katsi V, Skalis G, Pavidis AN, et al. Angiotensin receptor LCZ696: a novel targeted therapy for arterial hypertension? Eur Heart J. 2015;1:260–264.
   Web of Science ®Google Scholar
• Ruilope LM, Dukat A, Bohm M, et al. Blood pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomized, double blind, placebo controlled active comparator study. Lancet. 2010;375:1255–1266.
   PubMed Web of Science ®Google Scholar
• Kario K, Sun N, Chiang FT, et al. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension. A randomized, double-blind, placebo-controlled study. Hypertension. 2014;63:698–705.
   PubMed Web of Science ®Google Scholar
• Kario K, Tamaki Y, Okino N, et al. LCZ696, a first-in-class angiotensin receptor – neprilysin inhibitor: the first clinical experience in patients with severe hypertension. Hypertension. 2016;18:308–314.
   Google Scholar
• Ito S, Satoh M, Tamaki Y, et al. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Hypertens Res. 2017;38:269–275.
   Web of Science ®Google Scholar
• Chen HH, Burnett JC Jr. Clinical applications of the natriuretic peptides in heart failure. Eur Heart J. 2006;8(Suppl. E):E18-E25.
   Web of Science ®Google Scholar
• Lee CY, Burnett JC Jr. Natriuretic peptides and therapeutic applications. Heart Fail Rev. 2007;12:131–142.
   PubMed Web of Science ®Google Scholar
• De Bold AJ, Borenstein HB, Veress AT, et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981;2:89–94.
   Google Scholar
• Rubatu S, Sciarretta S, Valenti V, et al. Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implications in cardiovascular diseases. Am J Hypertens. 2008;21:733–741.
   PubMed Web of Science ®Google Scholar
• Wang TD, Tan RS, Lee HY, et al. Effects of sacubitril/valsartan (LCZ696) on natriuresis, dieresis, blood pressure, and NT-pro-BNP in salt sensitive hypertension. Hypertension. 2017;69:32–41.
   PubMed Web of Science ®Google Scholar
• Campbell DJ. Neprilysin inhibitors and bradykinin. Front Med. 2018;5:257.
   Web of Science ®Google Scholar
• Chrysant SG, Chrysant GS. Sacubitril/valsartan: a cardiovascular drug with pluripotential actions. Cardiovasc Diagn Ther. 2018;8:543–548.
   PubMed Web of Science ®Google Scholar
• Nalvaeva NN, Belyaev ND, Kerridge C, et al. Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front Aging Neurosci. 2014;6:236.
   PubMed Web of Science ®Google Scholar
• Webster CI, Burrell M, Olsson LL, et al. Engineering neprilysin activity and specificity to create a novel therapeutic for Alzheimer’s disease.PloS One. 2014;9:e104001
   Google Scholar
• Langenickel TH, Tsubouchi C, Ayalasomayajula S, et al. The effect of LZC696 (sacubitril/valsartan) on amyloid-ß concentrations in cerebrospinal fluid in healthy subjects. Br J Clin Pharmacol. 2016;81:878–890.
   PubMed Web of Science ®Google Scholar
• Iadecola C, Yaffe K, Biller J, et al. Impact of hypertension on cognitive function: A scientific statement from the American Medical Association. Hypertension. 2016;68:e67- e94.
   PubMed Web of Science ®Google Scholar
• Chrysant SG. Promising cardiovascular and blood pressure effects of the SGLT 2 Inhibitors: a new class of antidiabetic drugs. Drugs Today. 2017;53:191–202.
   PubMed Web of Science ®Google Scholar
• Markham A. Ertugliflozin: first global approval. Drugs. 2018;78:513–519.
   PubMed Web of Science ®Google Scholar
• Weir MR, Januszewicz A, Gilbert RE, et al. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens. 2014;16:875–882.
   PubMed Web of Science ®Google Scholar
• Townsend RR, Machin I, Ren J, et al. Reductions in mean 24-hour ambulatory blood pressure after 6-week treatment with canagliflozin in patients with type 2 diabetes mellitus and hypertension/. J Clin Hypertens. 2016;18:43–52.
   PubMed Web of Science ®Google Scholar
• Kinguchi S, Wakui H, Ito Y, et al. Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study). Cardiovasc Diabetol. 2019;18:110.
   PubMed Web of Science ®Google Scholar
• Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38:420–428.
   PubMed Web of Science ®Google Scholar
• Baker WL, Smyth LR, Riche DM, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:262–275.
   PubMed Web of Science ®Google Scholar
• Liu J, Pong A, Gallo S, et al. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019;18:59.
   PubMed Web of Science ®Google Scholar
• Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015;12:90–100.
   PubMed Web of Science ®Google Scholar
• Abdul-Ghani M, Del Prato S, Chilton R, et al. SGLT 2 inhibitors and cardiovascular risk: lessons learned from the EMPA-REG OUTCOME study. Diabetes Care. 2016;39:717–725.
   PubMed Web of Science ®Google Scholar
• Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
   PubMed Web of Science ®Google Scholar
• Neal B, Perkovic V, Mahaffey KM, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–357.
   PubMed Web of Science ®Google Scholar
• Cannon CP, McGuire DK, Pratley R, et al. Design and baseline characteristics of the eValuation of ERTugliflozin efficacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J. 2018;206:11–23.
   PubMed Web of Science ®Google Scholar
• Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res. 2015;12:78–89.
   PubMed Web of Science ®Google Scholar
• Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010;27:136–142.
   PubMed Web of Science ®Google Scholar
• Wright EM, Leo DDF, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733–794.
   PubMed Web of Science ®Google Scholar
• Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393:31–39.
   PubMed Web of Science ®Google Scholar
• Quamme GA, Freeman HJ. Evidence for a high-affinity sodium-dependent D-glucose transport system in the kidney. Am J Physiol Renal Physiol. 1987;253:1.
   Google Scholar
• Turner RJ, Moran A. Heterogeneity of sodium-dependent D-glucose transport sites along the proximal tubule: evidence from vesicle studies. Am J Physiol Renal Physiol. 1982;242:4.
   Google Scholar
• Vallon V, Platt KA, Cunard R, et al. SGLT 2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2010;22:104–112.
   PubMed Web of Science ®Google Scholar
• Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–334.
   PubMed Web of Science ®Google Scholar
• Mancia G, Cannon CP, Tikkanen I, et al. Impact of empagliflozin on blood pressure in patients with type 2 diabetes mellitus and hypertension by background antihypertensive medications. Hypertension. 2016;68:1355–1364.
   PubMed Web of Science ®Google Scholar
• Wilcox CS, Shen W, Boulton DW, et al. Interaction between the sodium-glucose-linked transporter 2 inhibitor dapagliflozin and the loop diuretic bumetanide in normal human subjects. J Am Heart Assoc. 2018;7:e007046.
   PubMed Web of Science ®Google Scholar
• Tentolouris A, Vlachakis P, Tzeravini E, et al. SGLT 2 inhibitors: a review of their antidiabetic and cardioprotective effects. Int J Environ Res Public Health. 2019;16:2965.
   Web of Science ®Google Scholar
• Meir C, Schwartz AV, Egger A, et al. Effects of diabetes drugs on the skeleton. Bone. 2016;82:93–100.
   PubMed Web of Science ®Google Scholar
• Blevins TC, Farooki A. Bone effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus. Postgrad Med. 2017;129:159–168.
   PubMed Web of Science ®Google Scholar
• Tang HL, Li DD, Zhang JJ, et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetic patients: a network and cumulative meta-analysis of randomized controlled studies. Diabetes Obes Metab. 2016;18:1199–1206.
   PubMed Web of Science ®Google Scholar
• Ruanpeng D, Ungprasert P, Sangtian J, et al. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Metab Res Rev. 2017;33.
   Web of Science ®Google Scholar
• Azharuddin M, Adil M, Ghosh P, et al. Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a systematic literature review and Bayesian network meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2018;146:180–190.
   PubMed Web of Science ®Google Scholar
• Williams B, McDonald TM, Morant S, et al. British Hypertension society’s PATHWAY Studies RGroup. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386:2059–2068.
   PubMed Web of Science ®Google Scholar
• Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, Evaluation, and management. A scientific statement from the American Heart Association. Hypertension. 2018;72:e53- e90.
   PubMed Web of Science ®Google Scholar
• Kolkhof P, Barfacker L. 30 years of mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234:T125- T140.
   PubMed Web of Science ®Google Scholar
• Bramlage P, Swift SL, Thoenes M, et al. Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease. Eur J Heart Fail. 2016;18:28–37.
   PubMed Web of Science ®Google Scholar
• Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective non-steroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64:69–78.
   PubMed Web of Science ®Google Scholar
• Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34:2453–2463.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy. A randomized clinical trial. JAMA. 2015;314:884–894.
   PubMed Web of Science ®Google Scholar
• Katayama S, Yamada D, Nakayama M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy. J Diabetes Compl. 2017;31:758–765.
   PubMed Web of Science ®Google Scholar
• Ruilope LM, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50:345–356.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing kidney failure and disease progression in diabetic kidney disease trial. Am J Nephrol. 2019;50:333–344.
   PubMed Web of Science ®Google Scholar
• Bakris G, Yang YF, Pitt B. Mineralocorticoid receptor antagonists for hypertension management in advanced chronic kidney disease. BLOCK-CKD Trial. Hypertension. 2020;76:144–149.
   PubMed Web of Science ®Google Scholar
• Haller H, Bertram A, Stahl K, et al. Finerenone: a new mineralocorticoid receptor antagonist without hyperkalemia: an opportunity in patients with CKD? Curr Hypertens Rep. 2016;18:41.
   PubMed Web of Science ®Google Scholar
• Liu LC, Schutte E, Gansevoort RT, et al. Finerenone: third generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease. Exp Opin Invest Drugs. 2015;24:1123–1135.
   PubMed Web of Science ®Google Scholar
• Yang Y, Liu C, Lin YL, et al. Structural insights into central hypertension regulation by human aminopeptidase A. J Biol Chem. 2013;288:25638–25645.
   PubMed Web of Science ®Google Scholar
• Marc Y, Llorens-Cortes C. The role of the brain renin-angiotensin system in hypertension: implications for new treatment. Progr Neurobiol. 2011;95:89–103.
   PubMed Web of Science ®Google Scholar
• Keck M, De Almeida H, Compere D, et al. NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor for treating hypertension. Hypertension. 2019;73:1300–1307.
   PubMed Web of Science ®Google Scholar
• Boitard SE, Marc Y, Keck M, et al. Brain renin-angiotensin system blockade with orally active aminopeptidase A inhibitor prevents cardiac dysfunction after myocardial infarction in mice. J Mol Cell Cardiol. 2019;127:215–222.
   PubMed Web of Science ®Google Scholar
• Bakris G, Bursztyn M, Gavras I, et al. Role of vasopressin in essential hypertension: racial differences. J Hypertens. 1997;15:545–550.
   PubMed Web of Science ®Google Scholar
• Bolineau L, Frugiere A, Marc Y, et al. Orally active aminopeptidase A inhibitors reduce blood pressure: a new strategy for treating hypertension. Hypertension. 2008;51:1318–1325.
   PubMed Web of Science ®Google Scholar
• Marc Y, Hamazzou R, Balavoine F, et al. Central antihypertensive effects of chronic treatment with RB150: an orally active aminopeptidase A inhibitor in deoxycorticosterone acetate-salt rats. J Hypertens. 2018;36:641–650.
   PubMed Web of Science ®Google Scholar
• Marc Y, Gao J, Balavoine F, et al. Central antihypertensive effects of orally active aminopeptidase A inhibitors I spontaneously hypertensive rats. Hypertension. 2012;60:411–418.
   PubMed Web of Science ®Google Scholar
• Azzizi M, Courand PY, Denolle T, et al. A pilot double-blind randomized placebo-controlled crossover pharmacodynamic study of the centrally active aminopeptidase A inhibitor, firibastat, in hypertension. J Hypertens. 2019;37:1722–1728.
   PubMed Web of Science ®Google Scholar
• Ferdinand KC, Balavoine F, Besse B, et al. Efficacy and safety of firibastat, a first-in-class brain aminopeptidase A inhibitor, in hypertensive overweight patients of multiple ethnic origins. A phase 2, open-label, multicenter, dose-titrating study. Circulation. 2019;140:138–146.
   PubMed Web of Science ®Google Scholar
• Kitamura K, Aihara M, Osawa J, et al. Sulfhydryl drug-induced eruption: a clinical and histological study. J Dermatol. 1990;17:44–51.
   PubMedGoogle Scholar
• Hickey KA, Rubanyi G, Paul RJ, et al. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol. 1985;248:C550–C556.
   PubMed Web of Science ®Google Scholar
• Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–415.
   PubMed Web of Science ®Google Scholar
• Dhaun N, Webb DJ. Endothelins in cardiovascular biology and therapeutics. Nat Rev Cardiol. 2019;16:491–502.
   PubMed Web of Science ®Google Scholar
• Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet. 1994;344:852–854.
   PubMed Web of Science ®Google Scholar
• Haynes WG, Ferro CJ, O’Kane KP, et al. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation. 1996;93:1860–1870.
   PubMed Web of Science ®Google Scholar
• Krum H, Viskoper RJ, Lacourciere Y, et al. The effect of an endothelin receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. N Engl J Med. 1998;338:784–790.
   PubMed Web of Science ®Google Scholar
• Nakov R, Pfarr E, Eberle S. Darusentan: an effective endothelin A receptor antagonist for treatment of hypertension. Am J Hypertens. 2002;15:583–589.
   PubMed Web of Science ®Google Scholar
• Weber MA, Black HR, Bakris G, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomized, double-blind, placebo-controlled trial. Lancet. 2009;374:1423–1431.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Lindholm LH, Black HR, et al. Divergent results using clinic and ambulatory blood pressures. A report of a darusentan-resistant hypertension trial. Hypertension. 2010;56:824–830.
   PubMed Web of Science ®Google Scholar
• Yuan W, Cheng G, Li B, et al. Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis. Blood Press. 2017;26:139–149.
   PubMed Web of Science ®Google Scholar
• Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809–918.
   PubMed Web of Science ®Google Scholar
• Belge C, Delcroix M. Treatment of pulmonary arterial hypertension with the dual endothelin receptor antagonist macitentan: clinical evidence and experience. Ther Adv Respir Dis. 2019;13:1–13.
   Web of Science ®Google Scholar
• Kaluski E, Cotter G, Leitman M, et al. Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension-a multi-center randomized study. Cardiology. 2008;109:273–280.
   PubMed Web of Science ®Google Scholar
• Zile MR, Bourge RC, Redfield MM, et al. Randomized, double-blind, placebo-controlled study of sitaxesartan to improve impaired exercise tolerance in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2:123–130.
   PubMed Web of Science ®Google Scholar
• Heerspink HKL, Andress DL, Bakris G, et al. Rationale and protocol of the study of diabetic nephropathy with AtRasentan (SONAR) trial: a clinical trial design novel to diabetic nephropathy. Diabetes Obes Metab. 2018;20:1369–1376.
   PubMed Web of Science ®Google Scholar
• Verweij P, Danaietash P, Flamiom B, et al. Randomized dose-response study of the new dual endothelin receptor antagonist aprocitentan in hypertension. Hypertension. 2020;75:956–965.
   PubMed Web of Science ®Google Scholar
• Wei A, Gu Z, Li J, et al. Clinical adverse effects of endothelin receptor antagonists insights from meta-analysis of 4894 patients from 24 randomized double-blind placebo-controlled clinical trials. J Am Heart Assoc. 2016;26:e003896.
   PubMedGoogle Scholar
• Derbyshire ER, Marletta MA. Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem. 2012;81:533–559.
   PubMed Web of Science ®Google Scholar
• Frollman M, Ackerstaff J, Redlich G, et al. Discovery of the soluble guanylate cyclase stimulator vericiguat (BAY 1021189) for the treatment of chronic heart failure. J Med Chem. 2017;60:5146–5161.
   PubMed Web of Science ®Google Scholar
• Greene SJ, Georghiade M, Borlaug BA, et al. The cGMP signaling pathway as a therapeutic target in heart failure with preserved ejection fraction. J Am Heart Assoc. 2013;2:e000536.
   PubMed Web of Science ®Google Scholar
• Georghiade M, Greene SJ, Butler J, et al. Effect of vericiguat, a soluble gunylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction, the SOCRATES-REDUCED randomized trial. JAMA. 2015;314:2251–2262.
   PubMed Web of Science ®Google Scholar
• Pieske B, Maggioni AP, Lam CSP, et al. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoRin heart failure patients with RRESERVED EF (SOCRATES-PRESERVED) study. Heart Fail. 2017;38:119–1127.
   Google Scholar
• Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018;72:e53- e90.
   PubMed Web of Science ®Google Scholar
• An JN, Lee JP, Jeon HJ, et al. Severe hyperkalemia requiring hospitalization: predictors of mortality. Crit Care. 2012;16:R225.
   PubMed Web of Science ®Google Scholar
• Rossignol P, Legrand M, Kosiborod M, et al. Emergency management of severe hyperkalemia: guideline for best practice and opportunities for the future. Pharmacol Res. 2016;11:585–591.
   Google Scholar
• Dunn JD, Benton WW, Orozco-Torrent Era E, et al. The burden of hyperkalemia in patients with cardiovascular and renal disease. Am J Manag Care. 2015;21:s307- s315.
   PubMed Web of Science ®Google Scholar
• Rosano GMC, Spoletini I, Agewall S. Pharmacology of the new treatments for hyperkalemia: patiromer and sodium zirconium cyclosilicate. Eur Heart J. 2019;21(Suppl A):A28- A33.
   Web of Science ®Google Scholar
• Agarwal R, Rossignol P, Romero A, et al. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomized, double-blind, placebo-controlled trial. Lancet. 2019;394:1540–1550.
   PubMed Web of Science ®Google Scholar
• Li L, Harrison SD, Cope MJ, et al. Mechanism of action and pharmacology of patiromer, a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia. J Cardiovasc Pharmacol Ther. 2016;21:456–465.
   PubMed Web of Science ®Google Scholar
• Pitt B, Anker SD, Bushinski DA, et al. PEARL-HF Investigators. Evaluation of the efficacy and safety of RLY5016, a polymer potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32:820–828.
   PubMed Web of Science ®Google Scholar
• Weir MR, Bakris GL, Bushinski DA, et al. OPAL-HK investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372:211–221.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Pitt B, Weir MR, et al. AMETHYST-DH investigators. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST_DH randomized clinical trial. JAMA. 2015;314:151–161.
   PubMed Web of Science ®Google Scholar
• Linder KE, Krawczynski MA, Laskey D. Sodium zirconium cyclosilicate (ZS-9): a novel agent for the treatment of hyperkalemia. Pharmacotherapy. 2017;36:923–933.
   Web of Science ®Google Scholar
• Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia. JAMA. 2014;312:3223–3233.
   Web of Science ®Google Scholar
• Peacock WF, Rafique Z, Vishnevskiy K, et al. Emergency potassium normalization treatment including sodium zirconium cyclosilicate: a phase II, randomized, double-blind, placebo controlled study (ENERGIZE). Acad Emerg Med. 2020;27:475–486.
   PubMed Web of Science ®Google Scholar
• Zannad F, Hsu BG, Maeda Y, et al. Efficacy and safety of sodium zirconium cyclosilicate for hyperkalaemia: the randomized, placebo-controlled HARMONIZE-Global study. ESC Heart Fail. 2020;7:55–65.
   Web of Science ®Google Scholar
• Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372:222–231.
   PubMed Web of Science ®Google Scholar
• Ash SR, Singh B, Lavin PT, et al. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int. 2015;88:404–411.
   PubMed Web of Science ®Google Scholar
• Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394.
   PubMed Web of Science ®Google Scholar
• Windecker S, Kolh P, Alfonso F, et al. ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association of Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35:2541–2619.
   PubMed Web of Science ®Google Scholar
• Capodanno D, Milluzzo RP, Angiolillo DJ. Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelol) in percutaneous coronary intervention; from pharmacology to indications for clinical use. Ther Adv Cardiovasc Dis. 2019;13:1753944719893274.
   Google Scholar
• Parker WAE, Storey RF. Pharmacology and potential role of selatogrel, a subcutaneous platelet P2Y12 receptor antagonist. Expert Opin Emerg Drugs. 2020;25:1–6.
   PubMed Web of Science ®Google Scholar
• Tricori P, Huang Z, Held C, et al. antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20–33.
   PubMed Web of Science ®Google Scholar
• Morrow DA, Braunwald E, Bonacva MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–1413.
   PubMed Web of Science ®Google Scholar
• Ungerer M, Rosport K, Bultmann A, et al. Novel antiplatelet drug revacept (dimeric glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation. 2011;123:1891–1899.
   PubMed Web of Science ®Google Scholar
• Alenazy F, Thomas MR. Novel antiplatelet targets in the treatment of acute coronary syndromes. Platelets. 2020 June;12:1–14.
   Google Scholar