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Latest advances in hypertension, cardiac care offer new options for patients
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BOSTON — Several new FDA drug approvals and recent data from large and small studies offer promising new treatment options for hypertension management and cardiac care, according to two speakers at the Cardiometabolic Health Congress.
Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart and Vascular Center and professor of medicine at Harvard Medical School, highlighted trials involving two recently approved antiplatelet therapies and a recent analysis of extended dual antiplatelet therapy (DAPT).
PEGASUS-TIMI 54
In the PEGASUS-TIMI 54 trial, use of the oral antiplatelet therapy ticagrelor (Brilinta, AstraZeneca) plus low-dose aspirin reduced the risk for CV death, MI or stroke in patients with MI within the previous 1 to 3 years, Bhatt said. Compared with placebo, patients assigned ticagrelor 90 mg (HR = 0.85; 95% CI, 0.75-0.96) and ticagrelor 60 mg (HR = 0.84; 95% CI, 0.74-0.95) had a lower risk for the primary efficacy outcome after a mean follow-up of 3 years.
Among patients with and without diabetes from the overall PEGASUS trial, researchers observed no significant between-group differences for overall MACE. However, results were different for the endpoint of coronary death, according to Bhatt.
“There seemed to be no effect in the nondiabetic patients; however, for diabetic patients, there was a significant reduction in coronary death favoring ticagrelor to placebo,” Bhatt, chief medical editor of Cardiology Today’s Intervention, said during his presentation.
DAPT trials
For a meta-analysis published in European Heart Journal in August 2015, researchers examined trials that compared longer vs. shorter-term DAPT in more than 33,000 high-risk patients with prior MI.
In the pooled analysis, extended DAPT decreased risk for MACE vs. aspirin alone and reduced CV death, with no increase in non-CV death. Extended DAPT also reduced MI, stroke and stent thrombosis, Bhatt said.
“Is there a price to pay (for extending DAPT)? Yes. No free lunch,” Bhatt said. “A 73% excess (risk) in major bleeding; about a 0.8% absolute risk excess. This isn’t fatal bleeding [or] … intracranial bleeding; it’s really all an increase in transfusions.”
Guidelines regarding extended-duration DAPT recommend 1 year of therapy for patients with stable CAD and a history of or a high risk for bleeding; extended DAPT is recommended for patients with ACS, diabetes, renal dysfunction and several other risk factors.
“I think the real decision about optimal duration of DAPT … is that there is really no ‘one size fits all,’” Bhatt said. “You have to be a doctor and customize therapy. Talk to the patient and reassess their risk. Patient-related factors, such as diabetes, ACS … all these things come into play.”
CHAMPION PHOENIX
In June 2015, the FDA approved cangrelor (Kengreal, The Medicines Company), an IV antiplatelet agent that prevents clot formation in the arteries, for patients undergoing PCI.
In the double blind, placebo-controlled CHAMPION PHOENIX trial, which compared cangrelor vs. clopidogrel in more than 10,000 patients, the drug was shown to reduce death, MI, and the rate of ischemic events, including stent thrombosis during PCI, with no significant increase in severe bleeding, Bhatt said.
In sensitivity analyses published in August in Circulation, which explored the effects of cangrelor on the 462 patients who sustained an MI using different definitions, researchers found that results persisted, according to Bhatt. When the Society for Cardiovascular Angiography and Interventions’ definition of periprocedural MI was applied to potential ischemic events, for example, there were fewer total MIs (n = 134); however, the effects of cangrelor on MI remained significant, according to researchers. Similar effects were observed when defining MI in other ways, Bhatt said.
“The event rate, numerically speaking, is lower the more specific the definition,” he said. “However, the effect size is larger. So, the exact same thing that was seen with a different antiplatelet therapy agent was seen here, too.”
Advances in hypertension
During a presentation, Keith C. Ferdinand, MD, professor of clinical medicine at Tulane University School of Medicine and Cardiology Today Editorial Board member, reported on several new developments in hypertension, including FDA approval a fixed-dose combination of nebivolol and valsartan tablets (Byvalson, Allergan). The drug, approved in June, is the only fixed-dose combination of a beta blocker and angiotensin II receptor blocker available in the United States.
In a double blind, placebo-controlled, dose-escalating, 8-week efficacy and safety study, which was conducted in approximately 4,100 patients with stage 1 or 2 hypertension, researchers observed greater reductions in both systolic and diastolic BP vs. nebivolol or valsartan alone, according to Ferdinand. Adverse events were similar across treatment groups. Maximum anti-hypertension effects were observed between 2 to 4 weeks, and increasing the dose does not result in any meaningful, further BP reduction, he said.
Nerve stimulation therapy
A median nerve modulator is not yet FDA-approved, but is currently undergoing study, Ferdinand said. The coin-sized, programmable, peripheral nerve neurostimulator is implanted subcutaneously in both forearms, where low-power electric currents stimulate the median nerves.
In a small, randomized, double-blind, sham-controlled study, 41 patients aged 45 to 84 years had a mean decrease in systolic BP of 10.31 mm Hg and a mean decrease in ambulatory BP of 4.68 mm Hg at 6 months. Two devices required removal and nine patients reported implant site inflammation, Ferdinand said.
He noted that “the sample size is small, this is just an early study and it is not conclusive.”
SPRINT and older patients
In an analysis of more than 2,600 ambulatory patients aged 75 years and older participating in the SPRINT trial, researchers observed a key finding: Treating to a systolic BP target of < 120 mm Hg vs. < 140 mm Hg resulted in lower rates of fatal and nonfatal major adverse CV events and death from any cause, Ferdinand said. There were no between-group differences observed for serious adverse events.
“SPRINT appears to suggest that, even in older persons, a more intense [BP] approach is the best approach,” Ferdinand said.
Medication timing
A study published in Diabetologia in February 2016 suggested that adults with hypertension who do not have diabetes have a lower risk for developing the disease with taking their BP medication at bedtime vs. adults who take the medication upon awakening, Ferdinand said.
In a randomized, prospective, open-label, blinded-endpoint trial, the researchers also found that adults who took antihypertensive medications at bedtime decreased their ambulatory BP, he added.
Participants were randomly assigned to ingest all BP-lowering medications upon awakening (n = 1,029) or to take the complete daily dose of one or more BP-lowering medications at bedtime and the remaining medications (if any) upon awakening (n = 983). During a mean of 5.9 years, 171 participants developed type 2 diabetes; 4.8% of cases in the bedtime group and 12.1% in the morning group. After adjustment for fasting glucose, waist circumference, ambulatory BP, “dipping” classification and chronic kidney disease, adults in the bedtime group had a significantly lower HR for new-onset diabetes (HR = 0.43; 95% CI, 0.31-0.61). – by Regina Schaffer
References:
Bhatt DL, Ferdinand KC. Late-Breaking Clinical Trials and FDA Update. Presented at: Cardiometabolic Health Congress; Oct. 5-8, 2016; Boston.
Hermida RC, et al. Diabetologia. 2015;doi:10.1007/s00125-015-3748-8.
Udell JA, et al. Eur Heart J. 2015;doi:10.1093/eurheartj/ehv443
Disclosure: Bhatt reports receiving grants or research support from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi and The Medicines Company. Ferdinand reports receiving grants, research support or consultant fees from Amgen, Boehringer Ingelheim, Eli Lilly and Sanofi.
Editor’s Note: This story was updated to clarify the references cited within the article.