Watson Clinic Launches Clinical Trial of Drug Treatment for Heart Failure
by TERESA SCHIFFER
There could be some good news on the horizon for patients who experience acute heart failure. The Watson Clinic Center for Research is beginning a new clinical trial study on a drug to treat this potentially life-threatening medical event. The trial is named DAPA ACT HF-TIMI 68. Board-certified interventional cardiologists Kevin Browne, Jr., MD, and Zia Rab, MD, are the doctors leading this clinical trial of the drug dapagliflozin.
Dapagliflozin is currently approved by the FDA primarily for use in patients who have type 2 diabetes. The sodium-glucose cotransporter-2 (SGLT2) inhibitor helps to improve blood sugar control by removing excess sugar from the body. This is done by helping the kidneys reabsorb glucose from the blood. For patients who are affected by type 2 diabetes as well as either cardiovascular disease or risk factors for cardiovascular disease, dapagliflozin can also reduce the risk of hospitalization due to heart failure. Research has shown that this drug can additionally reduce the risk of worsening heart failure or cardiovascular death in patients showing signs of chronic heart failure, regardless of whether they suffer from diabetes.
There are several other drugs in the SGLT-2 inhibitor family that function in a similar manner as dapagliflozin to lower blood sugar, such as empagliflozin (brand name Jardiance), canagliflozin (Invokana), and ertugliflozin (Steglatro). Dapagliflozin is sold under the brand name Farxiga, among others. As a family, SGLT-2 inhibitors have been approved and available since 2013, and since then have been investigated for their effectiveness and safety regarding cardiovascular health in diabetic patients. As a class, SGLT-2 inhibitors have been shown to reduce the risk of heart failure by an impressive 31 percent.
What makes dapagliflozin unique is its performance in the DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) trial, which was published in 2018. This was the first cardiovascular outcomes trial on a SGLT-2 inhibitor that included heart failure or cardiovascular death as one of its primary end points. When compared to a placebo in a broad population of patients with type 2 diabetes and either multiple cardiovascular risk factors or established atherosclerotic disease, dapagliflozin showed a statistically significant reduction in heart failure hospitalizations or cardiovascular deaths.
These findings are especially promising because the mortality rate for patients with heart failure caused by reduced heart muscle function is tragically high. The mortality rate at five years is 75 percent, while the hospital readmission rate is 82 percent. Rab explains that there is a drastic need for disease-modifying therapies for patients that can have an immediate impact on health without the risk of dose-limiting side effects. Dapagliflozin may offer protective effects on the heart through several distinct mechanisms as compared with other treatments that are currently in use. As an additional benefit, SGLT-2 inhibitors may also protect the kidneys, and renal disease can have a negative impact on heart failure outcomes.
It takes multiple doses of dapagliflozin to affect a patient’s blood sugar levels or their risk of heart failure. The drug is administered once per day. Participants in the DAPA ACT HF-TIMI 68 trial will receive one daily 10mg dose of either dapagliflozin or a placebo for two months. It is expected that the cardiovascular effects of the medication will be realized within about a week and continue for the duration of the therapy.
For a patient to be included in the Watson Clinic trial, they must be over 18 years of age, currently hospitalized for heart failure with ejection fraction (heart muscle function) of less than 40 percent, not suffer from kidney disease, not have liver failure, and not have used any SGLT-2 inhibitors in the preceding 30 days. Patients will be randomized into the study between 24 hours and seven days after their admission to the hospital, once their heart failure has been initially treated and stabilized, and while the patient remains hospitalized.
This drug cannot be given to patients who have exhibited a prior intolerance to SGLT-2 inhibitors, those who have hypoglycemia, hypotension, severe kidney or liver failure, have had a recent heart attack, or who are pregnant. Dapagliflozin has the potential to worsen hypoglycemia (low blood sugar) when used with insulin or other glucose-lowering medications. Possible side effects of this medicine can include dehydration, hypoglycemia, nausea, vomiting, urinary tract infection, other changes in urinary health, and yeast infections of the vagina or penis.
Patients who do not receive dapagliflozin will not be put at any additional risk of negative outcomes, as they will continue to receive the guideline-directed medical therapy already in place to reduce their risk of heart failure, cardiovascular death, serious renal complications, and further hospitalization. At the end of this trial, if all goes well, doctors will have an effective new tool on hand for helping their patients to live longer, fuller lives.