Next week the FDA will oversee a joint meeting of two advisory committees to take another look at RECORD, a clinical trial that involved the diabetes drug rosiglitazone. Motivations and political maneuverings aside, the event highlights the difficult balancing act facing physicians today.
Half a decade ago, the FDA placed two black box warnings on rosiglitazone (Avandia, GlaxoSmithKline) due to concerns over an increased risk of congestive heart failure and MI. In 2010, the FDA’s Encocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee took aim at RECORD, which was designed to compare Avandia with other drugs, and added more restrictions.
Fast forward to 2012, when GlaxoSmithKline paid a $3 billion fine after pleading guilty to counts that it misbranded two drugs and failed to report safety data on Avandia.
The FDA, pharmaceutical companies, physicians and patients recognize the need for drugs to treat the rising tide in diseases such as diabetes. Patients with cardiovascular diseases often have comorbidities such as diabetes, and diabetes is a risk factor for cardiovascular disease. New drugs need to be efficacious and safe, as shown in clinical trials. But the studies may not reflect the broader “real-world” patient population, or be sufficiently powered to detect rare adverse events.
Physicians who care for patients with nonvalvular atrial fibrillation also wrestle with this quandary. They now have the option of prescribing a thrombin inhibitor or direct factor Xa in lieu of vitamin K antagonists as anticoagulants for patients at risk of stroke but outcomes in clinical practice likely will differ from clinical trial results. Also, while the novel drugs offer potentially lower rates of bleeding and stroke, they as yet lack an antidote to reverse anticoagulation.
In the May 30 issue of the New England Journal of Medicine, three physicians offer recommendations for managing patients on antithrombotics who will undergo surgery or an invasive procedure. As they point out, 10 percent of people taking antithrombotic drugs need surgery or other procedures annually. The question is, how to reduce the risk of bleeding and stroke simultaneously.
It is a balancing act, based on evidence, clinical judgment and an individual patient’s needs and wants. In the meantime, the FDA and numerous registries, including the American College of Cardiology’s PINNACLE-AF registry, are conducting postmarket analyses on novel anticoagulants that will broaden understanding of benefits and risks.
Hopefully, the RECORD readjudication won’t prove to be a rehash of previous proceedings but instead will provide a platform for discussions of how to ensure pre- and postmarket transparency, better surveillance and ultimately a therapy that improves outcomes.
Candace Stuart, Cardiovascular Business, editor