New hope for heart failure patients

Managing patients with heart failure can be one of the most humbling challenges for doctors. The quality of life of these patients is significantly hampered and they’re not able to do the things they’d like to do, or must do because of easy fatigability or shortness of breath.

Despite current best standard of care, half of these patients (50 percent) will die in five years, and it is just as agonizing to the attending physician of these patients, as it is to the patients’ relatives, to see them gradually deteriorate and eventually die.

The degree of disability a patient experiences depends on the severity of the heart failure, which is classified from Class 1 to 4—Class 4 being the most severe with the patient experiencing signs and symptoms of heart failure even at rest.

Despite optimal doses of currently available medicines, many patients with heart failure could not even lie flat on bed when they sleep because this position aggravates the heart failure and wakes them up in the middle of the night feeling like they’re drowning. They have to prop themselves up with pillows to have a good night’s sleep.

Difficulty of breathing

Such was the case of D.G., a mother in her early 40s who had progressive difficulty of breathing noted after delivery of their third child. She was wondering why she was gaining weight after delivery and noticed that her legs also progressively became swollen or edematous. Soon she had to catch her breath after walking a short distance.

She was diagnosed to have postpartum cardiomyopathy—a cause for heart failure seen in women in the last month of pregnancy or within a few months after delivery. In these women, no prior underlying heart disease could be identified such as problems in the heart valves, clogging of the arteries or heart problems since birth (congenital heart disease). For a third or a half of these patients, the heart failure can be temporary; but in at least a third, it can progress to a severe, disabling and life-threatening heart failure.

We don’t know exactly what causes postpartum cardiomyopathy. Available laboratory examinations would suggest a swelling and weakening of the heart muscles making it unable to effectively pump out blood into the circulation. The scientists call this swelling or inflammation of the heart muscle as myocarditis, which has been attributed to inflammatory proteins that may be found in the blood during pregnancy.

Some researches suggest that the baby’s fetal cells could enter the mother’s bloodstream and can cause an adverse inflammatory reaction, leading to myocarditis. There is some evidence showing that the predisposition to develop postpartum cardiomyopathy may run in some families.

Other risk factors predisposing to postpartum cardiomyopathy include mother’s age over 30 years, multiparity (mothers having been pregnant and had delivered several times already), pregnancy with multiple fetuses, a history of elevation of the blood pressure during pregnancy (preeclampsia) or after delivery (postpartum hypertension) and history of substance abuse (alcohol or drugs).

First delivery

Our patient D.G. had her first pregnancy and delivery in her mid-30s and her blood pressure was noted to be high toward the latter part of her previous pregnancies and for a few months after delivery. Her symptoms though were a lot worse after her third delivery.

Aside from fluid and salt restriction, we gave her the usual medicines for heart failure but her response was not that good to allow her to do what she has to do ordinarily as a housewife and mother. Her 2-D echocardiogram, an ultrasound-like examination which evaluates the functioning of the heart, showed that her heart muscles were only half as effective in pumping the blood out of her heart; hence, the blood was flooding her lungs causing her shortness of breath.

New investigational drug

It was quite opportune that when she was referred to our clinic, we were taking part in a multicenter international trial (PARADIGM-HF) trying Novartis’ new investigational drug for heart failure coded as LCZ696. Although we, as the researchers, were blinded on what drug our patients were receiving, D.G. improved significantly while receiving whatever study drug was assigned to her, and that was all that mattered.

Two weeks ago, at the European Society of Cardiology congress in Barcelona, the principal PARADIGM-HF authors presented the results of the study showing that the new investigational heart failure medicine, LCZ696, was even superior to the tried-and-tested drug for heart failure—the ACE-inhibitor enalapril on key parameters or endpoints in this largest heart failure study ever done.

Patients given LCZ696 were more likely to be alive and less likely to have been hospitalized for sudden deterioration of their heart failure than those given enalapril. In the study, patients received LCZ696 or enalapril in addition to what is accepted as current best treatment for heart failure.

Magnitude of benefit

Subjecting the results to stringent statistical analysis, the authors showed that the magnitude of benefit with LCZ696 against enalapril was highly significant and clinically important. The clinical benefit was noted early, was sustained during the clinical trial and was consistent across various patient subgroups.

Specifically, LCZ696 reduced the risk of death from cardiovascular causes by 20 percent, reduced heart failure hospitalizations by 21 percent, reduced the risk of dying from any cause (all-cause mortality) by 16 percent, and reduced by 20 percent the composite measure of cardiovascular death or heart failure hospitalization.

Unque mode of action

LCZ696, given twice daily for heart failure, has a unique mode of action in reducing the strain on the failing heart. It enhances the production of hormones which are beneficial to failing hearts, while at the same time suppresses harmful hormones in the so-called renin-angiotensin system.

Side-effect profile of LCZ696 is also favorable and in PARADIGM-HF, it was shown to be better tolerated than enalapril.

“By demonstrating a very significant reduction in cardiovascular deaths while improving quality of life, LCZ696 represents one of the most important cardiology advances of the last decade,” said David Epstein, division head of Novartis Pharmaceuticals. Many heart failure experts present in the congress, including those who are usually critical of new drugs, expressed no disagreement to this statement.

Hopefully, LCZ696 will also turn out to be a life-changing drug that can extend the lives of millions of patients worldwide with heart failure, similar to the “magic pill” Sen. Miriam Defensor-Santiago said she’s taking for stage 4 lung cancer.

We certainly need more “magic pills” for our patients with life-threatening illnesses like heart failure, cardiovascular diseases and cancer—which remain the top killers worldwide. It is humbling that we cannot produce these “magic pills” as fast as we need them but that’s okay. Good medicines don’t come out of a hat like magicians do with pigeons. It takes a decade or two to produce a good drug. And there’s really no magic to the process.