Abstract
Interview by Tanya Stezhka
Dr Cooper-DeHoff is an Associate Professor in the Department of Pharmacotherapy and Translational Research, and the Department of Pharmaceutics in the College of Pharmacy, and in the Division of Cardiovascular Medicine, at the University of Florida (FL, USA). Her principle research focuses on hypertension, diabetes and the metabolic syndrome. She was a principle investigator of the INVEST study, which evaluated hypertension treatments in older coronary artery disease patients, and is currently a coinvestigator on two NIH grants evaluating pharmacogenetic hypertension associations. She is a member of the American Heart Association, American Society of Hypertension, American College of Cardiology and Florida Society of Hospital Pharmacists.
You currently serve as an Associate Professor at The University of Florida, Division of Cardiovascular Medicine (FL, USA). Could you tell us a little bit about your background & how you progressed to your current role?
I got my Pharm D degree at the University of California, San Francisco, School of Pharmacy (CA, USA) many years ago and during the course of my training and residency developed a specific interest in research and, being a trained pharmacist, drug research in particular. When I was looking for employment, I gravitated towards a role that allowed me to facilitate and carry out research in a hospital setting, which is what brought me to Gainesville (FL, USA). I started out by working at Shands at the University of Florida Teaching Hospital (FL, USA) and over the course of my employment developed some important working relationships with cardiologists in the field of hypertension, hypercholesterolemia and coronary artery disease (CAD). I was eventually hired as a faculty member at the University of Florida’s College of Medicine, Division of Cardiology. This gave me the opportunity to really develop some important clinical skills. After 10 years, there was a tenure track faculty opening at the University of Florida’s College of Pharmacy; however, while having officially moved, I have maintained very close working ties with the College of Medicine and the Division of Cardiology.
Expert Review of Cardiovascular Therapy turned 10 years of age in May this year. The research field of antihypertensives has progressed a great deal in this time. Could you walk us through the most important trials & findings that you have been involved in over the last decade?
My primary involvement would be with the INVEST study of which I was one of the founding and lead investigators. We focused on a population of patients who we felt were under-represented in clinical trials at that time. The inclusion criteria were patients who had documented CAD and hypertension. In many other studies, you would find 10–15% of the trial population had CAD, but our study was unique in that 100% of participants had CAD.
We decided to focus on two blood pressure treatment strategies: a calcium-antagonist strategy (verapamil and ACE inhibitor, trandolapril, followed by a hydrochlorothiazide diuretic) and a noncalcium antagonist strategy (patients started on β-blocker, atenolol, then added hydrochlorothiazide followed by trandolapril). We randomized 22,576 hypertensive CAD patients from around the world to the two treatment strategies and followed them for an average of approximately 3 years for outcomes that included nonfatal myocardial infarction, nonfatal stroke and all-cause death. The study started in 1996 and we published the primary results in JAMA 10 years ago in 2003.
What the INVEST study contributed to the literature was that the two treatment strategies were equally effective with regards to adverse cardiovascular outcomes. Before the study, people may have argued that the noncalcium agonist strategy was going to provide a better outcome because if a patient had CAD and a prior myocardial infarction, they were prescribed β-blockers. The INVEST trial showed that a patient on a heart-rate lowering calcium antagonist can do just as well on a β-blocker.
Are there any people or institutions who you feel have particularly influenced the progression of the field?
I think there are many people and many institutions that have influenced the field of hypertension based on the totality of important research we have had over the last 10 years. This research will certainly serve to inform the new guidelines that we have all been anxiously awaiting here in the USA for over a decade – the entire time Expert Review of Cardiovascular Therapy has been in print! I think anybody who has contributed to the literature by evaluating various forms of hypertension or antihypertensive treatments has helped; I cannot call on specifics because there are too many to count!
What is your view on the impact of current antihypertensive drugs in high-risk populations?
It is my personal belief that the right drug has to be prescribed at the right dose and the patient has to take the drug adherently and persistently. If all of these things happen, the drugs we have available are very effective, even in high-risk populations, at treating blood pressure. The problem we often find, especially in the community, is that there is some physician inertia about first identifying those who need antihypertensive treatment and then prescribing adequate doses of antihypertensive therapy. The problem at the patient level falls with adherence; hypertension is often asymptomatic unless it is very high so if a patient is prescribed an antihypertensive drug with adverse effects for a condition that was asymptomatic to begin with, they will most likely stop taking the drug. We are finding it hard to educate patients about how important treating hypertension is so the best we can do is work with the patients to find medication that lowers blood pressure with no adverse effects.
On the subject of physician–patient care, what changes to hypertensive patient care will be important in the coming 10 years?
I personally believe that we need to move away from a ‘cookbook’ guideline system where we treat the entire population of hypertensive patients in the same way. I think that what we have learned over the last decade is that approach does not work very well. We showed in our INVEST patients that there are some diabetic patients with CAD who may benefit from a very low blood pressure goal of less than 130/80 but other diabetic patients in whom if you lower the blood pressure to less than 130/80, they have higher mortality risk. And so I believe we need to move toward a more personalized patient focus rather than global care for these patients.
In your view, what high-risk population will gain the most focus in the coming 10 years?
I think the focus will still remain not only with diabetics but also patients with chronic kidney disease and stroke history. Those are the biggest high-risk groups who tend to have inadequate treatment with the highest level of potential risk.
How will healthcare reform in the USA impact hypertensive research & patient care?
That is an interesting question. I do not have much to do with the politics behind it, but I believe with regard to patient care, healthcare reform will make it better as insurance will become available to those who did not have it before, and then we can identify and treat hypertension or other important chronic conditions sooner. So I think from that perspective, it will be good. From a research perspective, at least at a federal level, it is becoming more difficult to obtain research funding so I think that although large federal initiatives like this benefit the general population, they may reduce dollars that might otherwise been spent on important clinical research.
As well as being involved in international trials, you are also coinvestigator on two NIH grants evaluating pharmacogenetic associations in hypertension. Could you tell us a bit about this work & where you feel this area is heading?
We have used these two grants to set up another clinical trial in hypertension patients, treating them for a shorter duration, and rather than look at outcomes like we did in the INVEST trial over the long term, we look at blood pressure responses. We studied patients for approximately 6 months, administering different drugs and obtaining DNA samples. We are planning to focus our work on identifying genes and gene variability that might affect the way one patient population will respond to a given specific antihypertensive agent compared with another. By respond, I mean not only with regards to how well it controls their blood pressure, which of course is very important, but also how well they might react with regards to adverse effects. For example, we know that some of the drugs we use to treat hypertension increase glucose; therefore, we could use genetics to identify who might be at increased risk of high glucose levels and then tailor a drug regime to that individual. We can also see who might respond very well, for example, to a β-blocker but not well at all to a calcium-channel antagonist, based on their genetic make up; we can chose the correct class of drugs to maximize the likelihood that the patient will respond well to initial treatment.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Expert Reviews Ltd.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.