Combination Pharmacotherapy to Prevent Cardiovascular Disease: Present Status and Challenges

European Heart Journal 35(6):353-364

14 Pages Posted: 28 May 2016

See all articles by Salim Yusuf

Salim Yusuf

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute; Hamilton Health Sciences; McMaster University

Amir Attaran

University of Ottawa - Common Law Section; University of Ottawa - Department of Epidemiology and Community Medicine

Jackie Bosch

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute; McMaster University

Philip Joseph

McMaster University

Eva Lonn

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute; Hamilton Health Sciences; McMaster University

Tara McCready

McMaster University

Andrew Mente

McMaster University

Robby Nieuwlaat

McMaster University

Prem Pais

St. John’s Medical College and Research Institute, Bangalore, India

Anthony Rodgers

University of Sydney - George Institute for Global Health

J-D Schwalm

McMaster University

Richard Smith

UnitedHealth Chronic Disease Initiative

Koon Teo

McMaster University

Denis Xavier

St. John’s Medical College and Research Institute, Bangalore, India

Date Written: November 27, 2013

Abstract

Combination pills containing aspirin,multiple blood pressure (BP) lowering drugs, and a statin have demonstrated safety, substantial risk factor reductions, and improved medication adherence in the prevention of cardiovascular disease (CVD). The individual medications in combination pills are already recommended for use together in secondary CVD prevention. Therefore, current information on their pharmacokinetics, impact on the risk factors, and tolerability should be sufficient to persuade regulators and clinicians to use fixed-dose combination pills in high-risk individuals, such as in secondary prevention. Long-term use of these medicines, in a poly pill or otherwise, is expected to reduce CVD risk by at least 50–60% in such groups. This risk reduction needs confirmation in prospective randomized trials for populations for whom concomitant use of the medications is not currently recommended (e.g.primary prevention). Given their additive benefits, the combined estimated relative risk reduction (RRR) in CVD from both lifestyle modification and a combination pill is expected to be 70–80%. The first of several barriers to the widespread use of combination therapy in CVD prevention is physician reluctance to use combination pills. This reluctance may originate from the belief that lifestyle modification should take precedence, and that medications should be introduced one drug at a time, instead of regarding combination pills and lifestyle modification as complementary and additive. Second, widespread availability of combination pills is also impeded by the reluctance of large pharmaceutical companies to invest in development of novel co-formulations of generic (or ‘mature’) drugs.A business model based on ‘mass approaches’ to drug production, packaging, marketing, and distribution could make the combination pill available at an affordable price, while at the same time providing a viable profit for the manufacturers.A third barrier is regulatory approval for novel multidrug combination pills, as there are few precedents for the approval of combination products with four or more components for CVD. Acceptance of combination therapy in other settings suggests that with concerted efforts by academics, international health agencies, research funding bodies, governments, regulators, and pharmaceutical manufacturers, combination pills for prevention of CVD in those with disease or at high risk (e.g. those with multiple risk factors) can be made available worldwide at affordable prices. It is anticipated that widespread use of combination pills with lifestyle modifications can lead to substantial risk reductions (as much as an 80% estimated RRR) in CVD.Heath care systems need to deploy these strategies widely, effectively, and efficiently. If implemented, these strategies could avoid several millions of fatal and non-fatal CVD events every year worldwide.

Keywords: Polypill, CVD, Hypertension

Suggested Citation

Yusuf, Salim and Attaran, Amir and Attaran, Amir and Bosch, Jackie and Joseph, Philip and Lonn, Eva and McCready, Tara and Mente, Andrew and Nieuwlaat, Robby and Pais, Prem and Rodgers, Anthony and Schwalm, J-D and Smith, Richard and Teo, Koon and Xavier, Denis, Combination Pharmacotherapy to Prevent Cardiovascular Disease: Present Status and Challenges (November 27, 2013). European Heart Journal 35(6):353-364, Available at SSRN: https://ssrn.com/abstract=2745493

Salim Yusuf (Contact Author)

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute ( email )

Canada

Hamilton Health Sciences ( email )

McMaster University Medical Centre
1200 Main Street West
Hamilton, Ontario L8S 4J9
Canada

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Amir Attaran

University of Ottawa - Department of Epidemiology and Community Medicine ( email )

451 Smyth Road
Ottawa, Ontario K1H 8M5
Canada

University of Ottawa - Common Law Section ( email )

57 Louis Pasteur Street
Ottawa, K1N 6N5
Canada
613-562-5800 ext: 2015 (Phone)
613-562-5659 (Fax)

Jackie Bosch

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute ( email )

Canada

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Philip Joseph

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Eva Lonn

David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI) - Population Health Research Institute ( email )

Canada

Hamilton Health Sciences

McMaster University Medical Centre
1200 Main Street West
Hamilton, Ontario L8S 4J9
Canada

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Tara McCready

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Andrew Mente

McMaster University

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Robby Nieuwlaat

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Prem Pais

St. John’s Medical College and Research Institute, Bangalore, India ( email )

Bangalore
India

Anthony Rodgers

University of Sydney - George Institute for Global Health ( email )

Level 10, King George V Building
83-117 Missenden Rd
Camperdown, NSW 2050
Australia

J-D Schwalm

McMaster University ( email )

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Richard Smith

UnitedHealth Chronic Disease Initiative ( email )

London
United Kingdom

Koon Teo

McMaster University

1280 Main Street West
Hamilton, Ontario L8S 4M4
Canada

Denis Xavier

St. John’s Medical College and Research Institute, Bangalore, India ( email )

Bangalore
India

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