Recent Trends in Clinical Trials for Coronary Diseases

Cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. Cardiovascular disease includes coronary artery diseases (CAD) such as angina and myocardial infarction. According to American Heart Association, the Centers for Disease Control and Prevention, the National Institutes of Health and other government sources, CAD and stroke account for 75% to 80% of CVD deaths, and 15.9% of all deaths. It causes more deaths and disability and incurs greater economic costs than any other illness in the developing and developed world. It is most likely to become the number one cause of death worldwide by 2020.

With hundreds of clinical studies being conducted every year, the causes, prevention, and/or treatment of all forms of cardiovascular disease remains to be active fields of biomedical research. Tremendous advances have occurred in therapies for coronary artery diseases, however, until recently it has not been attempted to examine the entire clinical trial portfolio for treatment of CAD.

In this study, Clinical Trials Transformation Initiative’s database for aggregate analysis of ClinicalTrials.gov (AACT) was used to evaluate the number of ongoing and completed interventional clinical trials for various coronary diseases. AACT is a PostgreSQL relational database containing information about clinical studies that have been registered at ClinicalTrials.gov.

The clinical trials database was queried for coronary diseases such as acute coronary syndrome (ACS), aneurysm coronary artery, chronic coronary total occlusions, coronary arteriosclerosis, coronary artery bypass grafting (CABG) and surgery, coronary artery disease, coronary artery occlusive disease, coronary atherosclerosis, coronary calcification, coronary heart disease (CHD), percutaneous coronary intervention (PCI), coronary restenosis, coronary stent implantation, coronary angiography and angioplasty. 

From January 1, 1997 to December 31, 2021, a total of 1,239 clinical studies (ongoing and completed) were registered at ClinicalTrials.gov. These clinical trials were analyzed from Phase I to IV development programs (Figure 1),

and across the agencies (industry, NIH, U.S. federal agencies, and other organizations such as research institutes, universities, etc., Figure 2).

Of these trials, 304 Phase III (25%) and 637 Phase IV (51%) trials were included in this study. A total of 259 (20.9%) phase 3 and 4 trials were sponsored by the industry. Among all the coronary disease categories compared (Figure 3),

the coronary artery disease (46%) was found to be the most prevalent indication, followed by acute coronary syndrome (16%), and coronary heart disease (11%). 

Company-sponsored Phase III and Phase IV clinical studies were further categorized by conditions specific to coronary disease, interventions, sponsors and year of completion. Novartis, Pfizer, GlaxoSmithKline, Merck, UCB Pharma, Bayer, Johnson & Johnson, Eli Lilly, and Bristol-Myers Squibb recorded maximum number of Phase III and Phase IV clinical trials, respectively (Figure 4).

Out of the 81 Phase III and 178 Phase IV trials being conducted by industry, 10 and 36 studies would be completed between 2018-2019, and between 2018- 2021 (data not shown), respectively. It is evident that, large number of post-marketing surveillance trials being conducted on several thousand volunteers having coronary diseases. 

The analysis resulted in a total of 62 company-sponsored Phase III and Phase IV trials recently conducted for coronary diseases. They are compared by phase, indication, intervention and sponsor for 2017-2021 period (Table 1).

The recent advances in drug developments for coronary disease patients included oral antithrombotic medications such as aspirin, clopidogrel (Plavix) and prasugrel (Effient, Efient). The anticoagulants consisted of the following drugs: heparin or unfractionated heparin (UFH), and enoxaparin (Lovenox, Clexane, Xaparin). Lipid-lowering agents as atorvastatin (Lipitor), ezetimibe (Zetia, Ezetrol) and rosuvastatin (Crestor, Rosulip, Zuvamor); and ticagrelor (Brilinta, Brilique, Possia) as a platelet aggregation inhibitor. 

The fact that CAD, CHD, PCI, and ACS had the highest number of trials registered, suggests that these three disease categories are considered as ‘high priority’ for cardiovascular drug development by the pharmaceutical industry.

Viren Konde is a Consulting Analyst for iHealthcareAnalyst, Inc.