This article is more than 5 years old. Information may no longer be current.
New CV approvals, indications, clarifications
Click Here to Manage Email Alerts
The FDA recently approved new indications for a novel oral anticoagulant and cardiac resynchronization therapy devices, approved a new stenting system to treat peripheral arterial disease, designated a genetic therapy for patients with HF as a breakthrough therapy, and clarified a warning about use of a drug to treat pulmonary arterial hypertension in children. Read more below.
Pradaxa available to treat DVT, PE
Dabigatran (Pradaxa, Boehringer Ingelheim) was approved by the FDA in April to treat deep vein thrombosis and pulmonary embolism in patients who have been on a parenteral anticoagulant for 5 days to 10 days, and to reduce the risk for recurrent DVT and PE in patients who were previously treated.
The approval was granted based on the results of four studies: RE-COVER, RE-COVER II, RE-MEDY and RE-SONATE. In RE-SONATE, dabigatran demonstrated superiority to placebo and in the others, the results demonstrated noninferiority to warfarin for reduction of recurrent DVT and PE.
New indication for CRT devices
The FDA in April approved Medtronic’s cardiac resynchronization therapy pacemakers and defibrillators for biventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction.
The approval was based on the results of the BLOCK HF trial, which found that patients in those populations assigned biventricular pacing had a 27% relative risk reduction for incidence of the composite study endpoint of heart size, HF-related hospitalization and mortality compared with those assigned right ventricular pacing.
The expanded indication applies to patients designated as NYHA Class I, II or III with AV block who are expected to require a high percentage of ventricular pacing, with LV ejection fraction ≤50%.
Peripheral stent system approved
The FDA approved the Supera Peripheral Stent System (Abbott Vascular) to treat blocked blood vessels in the upper leg due to PAD.
The stent, approved in March, is indicated to improve luminal diameter of the superficial femoral artery and proximal popliteal artery for lesion lengths up to 140 mm.
Breakthrough designation granted
The FDA in April designated Mydicar (Celladon Corp.), a novel, first-in-class genetic enzyme replacement therapy, as a breakthrough therapy.
Mydicar addresses a deficiency in the SERCA2a enzyme that causes the heart to pump inadequately in patients with HF, according to information from a company press release. The outpatient procedure, in which a nonpathogenic recombinant adeno-associated virus is administered directly to the heart, is intended for patients with HF of NYHA class III or IV who are adeno-associated virus NAb-negative.
The breakthrough therapy program is intended to streamline drug development and review of innovative new medicines that address certain unmet medical needs for serious or life-threatening diseases or conditions.
Warning on Revatio clarified
The FDA clarified its warning about use of sildenafil (Revatio, Pfizer) for treatment of pulmonary arterial hypertension in children.
Sildenafil is approved for treatment of PAH in adults. In August 2012, the agency issued a warning that the drug is not recommended for chronic use in children, citing clinical trial results showing higher rates of mortality in children assigned sildenafil. In March, the agency issued a clarification stating that the warning was not intended to advise that sildenafil should never be used in children, and that clinicians must weigh risks and benefits before prescribing the drug in children.
Jane W. Newburger
“Children with PAH and certain related conditions have limited available treatments, and sildenafil is an important option,” Jane W. Newburger, MD, MPH, of Children’s Hospital, Boston, told Cardiology Today in discussing the warning change. “This clarification should remove any barriers to prescribing the drug in the right circumstances. This issue highlights the important problem of the limited studies of drugs for rare pediatric diseases compared to more common adult conditions.” – by Erik Swain
Disclosure: Newburger reports no relevant financial disclosures.
Perspective
Back to Top
Stephan Moll, MD
On April 7, the FDA approved dabigatran for the treatment of venous thromboembolism based on the results of the phase 3 RECOVER and RECOVER II trials. The approved dose is 150 mg twice daily for patients with a creatinine clearance >30 mL/min.
A main caveat is that, for patients with acute VTE, the drug is approved only to be used after 5 to 10 days of initial parenteral anticoagulation based on the phase 3 clinical trial designs. The same caveat will, by the way, apply to edoxaban (Savaysa, Daiichi Sankyo) if/when it becomes FDA approved for the treatment of VTE. This need for an initial parenteral anticoagulant for the first 5 to 10 days before the oral anticoagulant drug is started is, obviously, a major disadvantage, as it complicates the anticoagulant management: The patient needs to learn how to inject low–molecular-weight heparin (LMWH) and has the expense of the costly LMWHs before being switched to the new oral anticoagulant.
Rivaroxaban (Xarelto, Janssen) and apixaban [Eliquis; Bristol-Myers Squibb, Pfizer] do not have this limitation. They were used immediately upon the diagnosis of VTE in the phase 3 acute VTE treatment trials, without the need for initial LMWH therapy, giving them a clear advantage in the management of acute VTE over dabigatran and edoxaban. As for the long-term secondary prevention of VTE, dabigatran is also not an attractive treatment option in this situation because of its twice-daily dosing schedule (many patients prefer a once-daily dosing regimen); high renal drug clearance and, thus, its dependence on renal function; and very wide range of inter-individual drug half-life, even in patients with normal renal function, making it impossible to know when prior to surgeries or procedures to stop the drug for effective hemostasis.
Thus, although this FDA approval is noteworthy, dabigatran is not an attractive option for VTE treatment for the patient and clinician when other, more convenient options are available, such as rivaroxaban at the moment and apixaban once/if it becomes FDA approved for VTE treatment. The only time I would see dabigatran as an option is if there is a financial advantage of the drug to the patient — ie, if it is treated preferentially by an insurance plan and a patient has less of a copay for dabigatran than for another one of the new oral anticoagulants — specifically rivaroxaban and, if/once FDA approved, apixaban. Finally, it is always good to have choices, even if it is only to keep drug prices down when competition exists. Thus, the approval of dabigatran is a welcome addition to our VTE treatment options.
Click Here to Manage Email Alerts