New trial results support treatment with Inspra (eplerenone) within first 24 hours of symptoms, in addition to standard therapy, in patients with acute STEMI without heart failure.

Sun Mar 10, 2013 2:03pm EDT

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Primary Composite Efficacy Endpoint Met in REMINDER trial
SAN FRANCISCO--(Business Wire)--
Pfizer Inc. (NYSE: PFE) today announced results from the REMINDER trial showing
statistically significant risk reductions in the primary composite efficacy
endpoint. The composite endpoint was defined as the time to first event of
cardiovascular (CV) mortality, re-hospitalization or extended initial hospital
stay due to diagnosis of heart failure (HF), sustained ventricular tachycardia
or fibrillation, ejection fraction (EF) ≤40% after 1 month, or an elevation of
BNP/ NT-proBNP after 1 month. 

The results were presented for the first time during the Late Breaker Clinical
Trial session at the 62nd Annual Scientific Session of the American College of
Cardiology in San Francisco today. 

The REMINDER trial was a randomized, double-blind trial, involving 1,012
patients with acute ST-segment elevation myocardial infarction (STEMI) without a
history of HF or EF <40% and without signs of HF. Patients received, preferably
before myocardial reperfusion, either eplerenone (25-50 mg OD) or placebo in
addition to standard therapy. Treatment was initiated within the first 24 hours
of symptom onset (preferably within first 12h). 

The REMINDER trial demonstrated a statistically significant 42.9% relative risk
reduction in the primary endpoint with p < 0.0001 (95% confidence interval [CI]
0.439, 0.742) in patients with acute STEMI when eplerenone was initiated within
the first 24 hours of onset of symptoms. Overall, the adverse events reported in
the REMINDER trial were consistent with those already known for eplerenone,
primarily hyperkalemia. 

Eplerenone is not approved for use in the patient population studied in the
REMINDER trial in any market. 

The improvement in outcome was mainly driven by a significant reduction of the
BNP / NT-proBNP biomarker component at 1 month. BNP/NT-proBNP has been shown to
be an important marker for short- and long-term prognosis in patients with
myocardial infarction in the presence or absence of preserved ejection fraction.
An elevation of BNP / NT-proBNP after 1 month was observed less frequently in
the eplerenone group 81(16.0%) than in the placebo group 131(25.9%) (adjusted
HR, 0.584; 95% CI 0.441-0.773; p=0.0002). 

Over the course of the study, the incidence of hyperkalemia (elevated potassium
defined as serum potassium levels exceeding 5.5 mEq/L) occurred in 5.6% vs. 3.2%
(p=0.09) in the eplerenone and placebo groups, respectively. Hypokalemia (serum
potassium level below 3.5 mEq/L) occurred more frequently in the placebo group
with 1.4% vs. 5.5% (p=0.0002) in the eplerenone and placebo groups,
respectively. The rates of other adverse events were similar in both groups. 

Commenting on the findings, the chair of the REMINDER Steering Committee
Professor Gilles Montalescot, Institute of Cardiology, Centre Hospitalier
Pitié-Salpêtriėre, Paris, France said: "Eplerenone improved the outcome of
patients presenting with acute STEMI and without concomitant heart failure. This
benefit was obtained in a low-risk population that was well treated, without
serious adverse drug effect. Adding eplerenone to standard therapy as early as
within the first 24 hours of symptoms reduced heart failure-related morbidity." 

About the REMINDER trial

The REMINDER trial was a randomized, double-blind trial, involving 1012 patients
with acute STEMI without a history of HF or EF <40% and without signs of HF. 

The REMINDER trial was conducted in 11 countries: Canada, Czech Republic,
France, Germany, Greece, Hungary, Netherlands, Poland, Slovakia, Spain, UK. 

The primary objective of the REMINDER trial was to assess the efficacy of Inspra
25 -50 mg once daily, compared to placebo, in the early treatment of acute
ST-segment elevation myocardial infarction (STEMI) within 24 hours (preferably
within the first 12h). 

The mean follow-up time was 10.5 months. 

The study was funded by Pfizer. 

About INSPRA®

INSPRA® (eplerenone) is a steroid nucleus-based mineralcorticoid receptor (MR)
antagonist with a higher degree of selectivity than spironolactone. 

Important Prescribing Information

In the United States, Inspra (eplerenone) is indicated to improve survival of
stable patients with left ventricular (LV) systolic dysfunction (ejection
fraction less than or equal to 40%) and clinical evidence of congestive heart
failure (CHF) after an acute myocardial infarction (MI). Eplerenone is also
indicated for the treatment of hypertension. Eplerenone may be used alone or in
combination with other antihypertensive agents. 

Eplerenone is contraindicated in all patients with serum potassium greater than
5.5 mEq/L at initiation, creatinine clearance less than or equal to 30 mL/min,
or concomitant administration of strong CYP3A4 inhibitors. Eplerenone is also
contraindicated for the treatment of hypertension in patients with type 2
diabetes with microalbuminuria, serum creatinine greater than 2.0 mg/dL in males
or greater than 1.8 mg/dL in females, creatinine clearance less than 50 mL/min,
or concomitant administration of potassium supplements or potassium sparing
diuretics. 

Serum potassium should be measured before initiating eplerenone therapy, within
the first week, and at one month after the start of treatment or dose
adjustment. Serum potassium should be assessed periodically thereafter,
especially in patients at risk for the development of hyperkalemia such as
elderly patients with renal insufficiency and patients with type 2 diabetes and
microalbuminuria. 

Most common adverse reactions (greater than 2% and more frequent than with
placebo) in patients with CHF Post-MI: hyperkalemia and increased creatinine.
Most common adverse reactions (greater than or equal to 2% and more frequent
than with placebo) in hypertensive patients: dizziness, diarrhea, coughing,
fatigue and flu-like symptoms. 

In the European Union, eplerenone is indicated, in addition to standard optimal
therapy, to reduce the risk of cardiovascular mortality and morbidity in adult
patients with NYHA class II (chronic) heart failure and left ventricular
systolic dysfunction (LVEF ≤30%). Eplerenone is also indicated to reduce the
risk of cardiovascular mortality and morbidity in stable patients with left
ventricular dysfunction (LVEF ≤40%) and clinical evidence of heart failure after
recent myocardial infarction. 

In Japan, eplerenone is approved for the treatment of hypertension. 

For additional product information in the US, visit:
http://media.pfizer.com/files/products/uspi_inspra.pdf

UK prescribing information is available at:
http://www.medicines.org.uk/EMC/medicine/16746/SPC/Inspra+25mg+%26+50+mg+film-coated+tablets/

Other countries should refer to local prescribing information. 

Pfizer Inc.: Working together for a healthier world

At Pfizer, we apply science and our global resources to improve health and
well-being at every stage of life. We strive to set the standard for quality,
safety and value in the discovery, development and manufacturing of medicines
for people and animals. Our diversified global health care portfolio includes
human and animal biologic and small molecule medicines and vaccines, and many of
the world's best-known consumer products. Every day, Pfizer colleagues work
across developed and emerging markets to advance wellness, prevention,
treatments and cures that challenge the most feared diseases of our time.
Consistent with our responsibility as the world's leading biopharmaceutical
company, we also collaborate with health care providers, governments and local
communities to support and expand access to reliable, affordable health care
around the world. For more than 150 years, Pfizer has worked to make a
difference for all who rely on us. To learn more about our commitments, please
visit us at www.pfizer.com. 

# # # # # 

DISCLOSURE NOTICE: The information contained in this release is as of March 10,
2013. Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future events or
developments.

This release contains forward-looking information about a potential additional
indication for Inspra, including its potential benefits, that involves
substantial risks and uncertainties. Such risks and uncertainties include, among
other things, the uncertainties inherent in research and development; whether
and when supplemental drug applications may be filed with regulatory authorities
for this potential additional indication for Inspra; decisions by regulatory
authorities regarding whether and when to approve any supplemental drug
applications that may be filed for this potential additional indication for
Inspra as well as their decisions regarding labeling and other matters that
could affect its availability or commercial potential; and competitive
developments.

A further list and description of risks and uncertainties can be found in
Pfizer`s Annual Report on Form 10-K for the fiscal year ended December 31, 2012,
and in its reports on Form 10-Q and Form 8-K.

Pfizer Inc.
(Media)
MacKay Jimeson , 212-733-2324
MacKay.Jimeson@pfizer.com
or
(Investors)
Suzanne Harnett, 212-733-8009
Suzanne.Harnett@pfizer.com

Copyright Business Wire 2013

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