Cardiac Safety Research Consortium Update

Cardiogenic shock: Defining the clinical and regulatory landscape

Written on behalf of the Cardiac Safety Research Consortium

The Cardiac Safety Research Consortium Think Tank, titled “Defining the Clinical and Regulatory Landscape for Cardiogenic Shock,” was convened in September. Clinical experts, FDA and Canadian regulators and industry leaders met to discuss current clinical best practices and brainstorm endeavors to efficiently generate evidence to guide future care of cardiogenic shock — a growing, highly morbid and fatal condition.

The meeting, from which a manuscript will shortly be forthcoming, addressed the following:

Marc Samsky
  • a review of pathophysiology, epidemiology and current clinical best practices;
  • review of evidence to date, as well as identification of barriers to ongoing prospective research; and
  • novel statistical and methodological approaches, intended use and appropriate outcomes for generating data and evidence that are acceptable from a regulatory standpoint.

Poor outcomes persist

Cardiogenic shock remains a leading cause of in-hospital mortality associated with acute MI.

Improved pre-hospital emergency care, timely revascularization and advances in PCI techniques resulted in a decrease in the incidence of acute MI with cardiogenic shock and associated mortality from 1970 through the early 21st century. Unfortunately, outcomes have not continued to improve. From 2003 to 2010, data show a near doubling in the incidence of acute MI with cardiogenic shock, with an associated 30-day mortality of nearly 40%.

In addition to acute MI, recognition of other etiologies of cardiogenic shock with associated poor outcomes include progressive HF, fulminant myocarditis and after cardiac surgery.

Innovation in trial design and adoption of novel management strategies have been slow. Since the SHOCK trial opened enrollment in 1993, only 2,500 patients (0.5% of acute MI with cardiogenic shock) have been enrolled in prospective, randomized trials worldwide. Moreover, it took nearly 40 years from development of the intra-aortic balloon pump in the 1960s to the first randomized controlled trial studying its efficacy via the IABP-SHOCK trial.

A growing need

A growing need, even in the absence of prospective, randomized evidence to support use, has led to widespread deployment of novel devices for the management of cardiogenic shock. From a regulatory standpoint, demonstration of improvement in the mean arterial pressure, so that targeted therapies can be deployed to treat underlying etiologies of cardiogenic shock, has been sufficient to approve therapies for shock.

Although significant challenges remain in the care of patients with cardiogenic shock, with the aid of stakeholders across advocacy groups, academia, industry and international regulatory agencies, the Cardiac Safety Research Consortium hopes in future meetings to establish uniform definitions of cardiogenic shock and to crystallize a plan to efficiently generate evidence to further guide care and improve outcomes.

Disclosure: Samsky reports no relevant financial disclosures.

Editor’s note: The Cardiac Safety Research Consortium Update is a new feature in Cardiology Today that will be published throughout the year when updates from CSRC are available. It is edited by Peter R. Kowey, MD, the Arrhythmia Disorders Section Editor for Cardiology Today. Email the editors at cardiology@healio.com for more information.

Written on behalf of the Cardiac Safety Research Consortium

The Cardiac Safety Research Consortium Think Tank, titled “Defining the Clinical and Regulatory Landscape for Cardiogenic Shock,” was convened in September. Clinical experts, FDA and Canadian regulators and industry leaders met to discuss current clinical best practices and brainstorm endeavors to efficiently generate evidence to guide future care of cardiogenic shock — a growing, highly morbid and fatal condition.

The meeting, from which a manuscript will shortly be forthcoming, addressed the following:

Marc Samsky
  • a review of pathophysiology, epidemiology and current clinical best practices;
  • review of evidence to date, as well as identification of barriers to ongoing prospective research; and
  • novel statistical and methodological approaches, intended use and appropriate outcomes for generating data and evidence that are acceptable from a regulatory standpoint.

Poor outcomes persist

Cardiogenic shock remains a leading cause of in-hospital mortality associated with acute MI.

Improved pre-hospital emergency care, timely revascularization and advances in PCI techniques resulted in a decrease in the incidence of acute MI with cardiogenic shock and associated mortality from 1970 through the early 21st century. Unfortunately, outcomes have not continued to improve. From 2003 to 2010, data show a near doubling in the incidence of acute MI with cardiogenic shock, with an associated 30-day mortality of nearly 40%.

In addition to acute MI, recognition of other etiologies of cardiogenic shock with associated poor outcomes include progressive HF, fulminant myocarditis and after cardiac surgery.

Innovation in trial design and adoption of novel management strategies have been slow. Since the SHOCK trial opened enrollment in 1993, only 2,500 patients (0.5% of acute MI with cardiogenic shock) have been enrolled in prospective, randomized trials worldwide. Moreover, it took nearly 40 years from development of the intra-aortic balloon pump in the 1960s to the first randomized controlled trial studying its efficacy via the IABP-SHOCK trial.

A growing need

A growing need, even in the absence of prospective, randomized evidence to support use, has led to widespread deployment of novel devices for the management of cardiogenic shock. From a regulatory standpoint, demonstration of improvement in the mean arterial pressure, so that targeted therapies can be deployed to treat underlying etiologies of cardiogenic shock, has been sufficient to approve therapies for shock.

Although significant challenges remain in the care of patients with cardiogenic shock, with the aid of stakeholders across advocacy groups, academia, industry and international regulatory agencies, the Cardiac Safety Research Consortium hopes in future meetings to establish uniform definitions of cardiogenic shock and to crystallize a plan to efficiently generate evidence to further guide care and improve outcomes.

Disclosure: Samsky reports no relevant financial disclosures.

Editor’s note: The Cardiac Safety Research Consortium Update is a new feature in Cardiology Today that will be published throughout the year when updates from CSRC are available. It is edited by Peter R. Kowey, MD, the Arrhythmia Disorders Section Editor for Cardiology Today. Email the editors at cardiology@healio.com for more information.