LCZ696 DRUG PROTECTS HEART FROM CARDIAC RUPTURE AFTER MYOCARDIAL INFARCTION
At present, there are many kinds of drugs for heart failure. the new drug LCZ696 (sacubitril/valsartan) is the first approved agent of a novel class of agents combining a neprilysin inhibitor and an ARB. There are currently no alternatives in this class is recommended by US guidelines as a first-line treatment for chronic heart failure. LCZ696 is better than conventional drugs at reducing cardiac death and hospitalization due to heart failure.
Heart disease is the leading cause of death in the world, and the majority of those deaths are caused by heart failure and acute myocardial infarction. In the past, angiotensin-converting enzyme inhibitors (ACE inhibitors) or Angiotensin II Receptor Blockers (ARBs) were used in combination with other drugs as the initial therapy for heart failure and acute myocardial infarction. ACE inhibitors and ARBs both inhibit the system responsible for regulating blood pressure, the Renin-Angiotensin-Aldosterone System (RAAS), which causes high blood pressure when it becomes overactive.
LCZ696 is a novel drug that combines Valsartan, a traditional antihypertensive drug, and Sacubitril, which has an organ-protective effect. Sacubitril inhibits neprilysin which decomposes hormones secreted mainly from the heart called Atrial Natriuretic Peptide (ANP), and B-type Natriuretic Peptide (BNP). A 2014 large-scale clinical trial of patients who had chronic heart failure with reduced ejection fraction (the percentage of blood exiting the heart at each contraction) reported that the number of cardiac deaths and re-hospitalization due to heart failure was reduced significantly with LCZ696 treatment than with existing ACE inhibitors. LCZ696 is now widely used in Europe and the United States as the first treatment for chronic heart failure.In addition, microscopic observations of the pathological tissue of the heart showed that the number of inflammatory cells was unchanged in all groups, but the activity of MMP-9 was clearly lowered in the LCZ696 treatment group. Furthermore, in experiments using cultured mouse macrophages, researchers confirmed that the inflammation action of cytokines and MMP-9 can be more suppressed using LCZ696 rather than using valsartan or sacubitril by themselves.
“LCZ696 is a new therapeutic drug that improves the prognosis of patients with chronic heart failure,” said Dr Masanobu Ishii of Kumamoto University. “We know that ischemic heart disease, especially myocardial infarction, is one of the causes of chronic heart failure and our study revealed that LCZ696 has a cardioprotective effect against myocardial infarction.”
“This improves a patient’s prognosis by suppressing cardiac rupture,” added Associate Professor Koichi Kaikita. “In the future, it is expected that LCZ696 will be used not only to treat chronic heart failure but also as therapy after acute myocardial infarction.”
This research result was presented at the Hot Line of the European Cardiology Society held in Barcelona, Spain, on 26-30 August 2017, and posted online in the “JACC; Basic to Translational Science” on 28 August 2017.