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Optimizing current and integrating new treatments to improve patient outcomes: experience from clinical practice (Part 2)

Michele Senni (Italy)

Michele Senni shares a clinical case of a patient from his clinical practice who experienced low blood pressure during treatment optimization.



Optimizing current and integrating new treatments to improve patient outcomes: experience from clinical practice - Michele Senni

Optimizing current and integrating new treatments to improve patient outcomes: experience from clinical practice - Michele Senni

Jill Riley: I’m Jill Riley, I’m from London in the United Kingdom. As you know already, I’m a nurse by background and I work at Imperial College, one of the universities of London.

Tiny Jaarsma: I’m Tiny Jaarsma, I’m a Professor in Nursing in Sweden.

Hobbs: I’m Richard Hobbs, I’m an academic primary care physician from Oxford and have done many epidemiological studies around heart failure over the years.

Frank Ruschitzka: We are going to talk about multidisciplinary management very soon in the second part of this symposium to bring it all together and this is a multidisciplinary approach, this is how our patients these days are managed. That got, by the way, rated a 1A recommendation, so Michele, all yours.


Thank you, Frank.


These are my disclosures.

Medical history...

Okay, let’s start with this case. It is an 84 years old, female, obese and she started to have hypertension, dyslipidemia and Type 2 diabetes in 2007.

Medical history: Oct 2007, 75 yo

She experienced the first hospitalisation for acute heart failure in October, 2007 at 75 years old. The echo showed an ejection fraction of 20% with a dilated left ventricle. In the EKG we appreciate a left bundle branch block. The blood chemistry, she has high glycaemia and then the NTproBNB was greater than 1700.

Coronary angiography

The coronary angiography showed normal vessels.


75 yo, female, with DM, HTN, dyslipidemia & hypokinetic cardiomyopathy

The medical therapy at discharge was nebivolol, 5mg, furosemide, 75mg, potassium canreonate, 50mg, aspirin, 100mg, Ramipril, 2.5mg, simvastatin, 20mg and then she took some anti-diabetic oral therapy.

Medical history: July 2008, 76 yo

In July, 2008 she had this outpatient visit in which she was New York heart function class IIb, EF improved to 35-40% and we up-titrated the nebivolol to 5mg bid. We couldn’t up-titrate the ACE-I due to the low blood pressure.

Speaker: Why was the patient on aspirin again?

Senni: 100mg.

Speaker: Why?

Senni: I don’t know. It’s true.

Medical history: March 2012, 80 yo

The second hospitalisation for worsening heart failure was in March, 2012. She had a reduced ejection fraction from the previous one from 35-40% to 25% and the QRS duration was 200 ms and therefore an ICD-CRT was implanted.

Medical history: March 2012, 80 yo

This is the summary of the EF, NTproBNP and the hospitalisation, the summary of the medical history.

Medical history: Oct 2012, 80 yo

In October, 2012 she had an outpatient visit where she had a NY functional class III, the ejection fraction was 33% and the blood pressure was 105/77 mmHg. The heart rate was 78 beats per minute, therefore we started with ivabradine, 2.5 bid and later up-titrated to 5mg bid.

Blood chemistry: Oct 5th, 2012

The blood chemistry showed mild anaemia and also NTproBNP had risen to 2180 bg/ml.

Echocardiogram: Oct 5th, 2012

This is her echocardiogram that shows an ejection fraction of 33%, a very dilated left ventricle with a pseudonormal pattern and an E/E of 16 and a mild pulmonary hypertension.


Therefore at that time we decided to enrol this patient in the Titration study. I have to say that in Italy, LCZ696 is not yet available on the market, therefore my experience comes from several studies in which I participated which were Paradigm, Paragon, Paramount and the Paradigm extension. This study is the Titration study.

This study was designed to understand, to realise which is the best up-titration modalities in patients that were taking an ACE-inhibitor or ARBs.

After a short run-in period of 50mg bid of LCZ the patients, 498 patients were enrolled in two different arms. The first arm was the conservative arm over six weeks and the second arm is a condensed arm over three weeks in which the LCZ was up-titrated from 100mg bid to 200mg bid.

Two subgroups were prespecified, the high RASi and the low RASi according to the dosage of ACE-inhibitor or ARBs.

Outpatient F-UP Visit 4 TITRATION June 13th, 2014

Coming back to our patient, at the visit four, the patient complained of this pressure. She had 88/55 mmHg, therefore we decided to down-titrate the LCZ. Of course we didn’t know which dose it was and we decided to discontinue the furosemide.

Outpatient F-UP Visit 5 TITRATION July 7th, 2014

At the visit five, the blood pressure increased to 115/68 mmHg and therefore we were able to up-titrate the LCZ another time.

Outpatient F-UP Visit 7 (EOS) August 6th, 2014

At the visit at the end of the study, the patient improved her clinical status since she was in functional class New York Heart Association II, the blood pressure was 105/70 mmHg, heart rate 58 beats per minute.


We unblinded the data, so we have figured out that this patient was in the condensed arm and this explains why we had to reduce the dosage of LCZ and to stop the furosemide at this level.

The Titration was just published last week and the data of this patient are in line with what we have found in the Titration study, in which the patients in the low RASi subgroup you see had more hypotension defined as systolic blood pressure less than 95 mmHg compared to the patients that were treated in the condensed arm.


Moreover, when we look at the treatment success defined as the proportion of patients who achieved and maintained the LCZ696 200mg bid without any interruption or down-titration over 12 weeks, you see clearly that patients that were treated, such as our patient, in the condensed arm reach a lower result in terms of treatment success compared to the conservative.

I think I can conclude my presentation and I am ready for some questions. Frank.

Ruschitzka: Thank you Michele, that was wonderful. [Applause]

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