The Year in Review: PCSK9 inhibitors, FDA approvals and deals aplenty

In 2015, the FDA approved numerous cardiovascular medications and devices, providing clinicians with new treatment options. Still, the prices of the treatments received scrutiny as the federal government and private insurers began paying closer attention to value and whether the benefits outweigh the costs.

As far as clinical trials, the SPRINT study presented at the American Heart Association (AHA) Scientific Sessions received the most hype and led to debates on if the results will change practice. The results showed that patients who had a systolic blood pressure target of less than 120 mm Hg had a 25 percent lower relative of the primary composite outcome of MI, other acute coronary syndromes, stroke, heart failure or death from cardiovascular causes compared with those who had a target of less than 140 mm Hg. Current guidelines recommend a target of less than 140 mm Hg in healthy adults and 130 mm Hg for adults with kidney disease.

Here are other highlights from the year in cardiology:

PCSK9 Inhibitors

In the summer, the FDA approved the first two proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors: alirocumab (Praluent, Regeneron Pharmaceuticals and Sanofi Aventis) and evolocumab (Repatha, Amgen).

Both drugs were shown in trials to significantly lower low-density lipoprotein (LDL) cholesterol. However, some experts were concerned that the drugs were approved before they were found to be effective at preventing or delaying major adverse cardiovascular events, including MI, ischemic stroke and death due to cardiovascular disease.

Trials are underway to determine both drugs’ effects on cardiovascular outcomes. Amgen recently noted that topline results of the FOURIER outcomes trial for evolocumab are expected to be released in the second half of 2016. Results of the alirocumab trial are expected to be released by 2017.

The costs of the PCSK9 inhibitors also were a hot topic.

The annual wholesale acquisition cost is $14,600 for alirocumab and $14,100 for evolocumab. The Institute for Clinical and Economic Review, a nonprofit healthcare research organization, released a report that said the price should be between $3,615 and $4,811 per year based on their overall benefits.

The drug manufacturers received good news in October when Express Scripts announced it would include both PCSK9 inhibitors on its national preferred formulary, which covers approximately 25 million people in the U.S.

Still, expect the debate on the value of PCSK9 inhibitors to continue in 2016 and beyond.

Mergers and acquisitions

The biggest deal of 2015 occurred in January, when Medtronic completed its acquisition of Covidien for nearly $50 billion. The companies are major medical manufacturers of cardiovascular devices, including implantable cardiac therapies such as pacemakers and defibrillators, valves, catheter-based ablation systems, stents and vascular and peripheral technologies. The combined company is now headquartered in Ireland, which has a lower tax rate than the U.S.

Medtronic made a slew of smaller acquisitions throughout the year. It agreed to acquire CardioInsight Technologies, Aptus Endosystems, RF Surgical Systems, Twelve, Medina Medical, Lazarus Effect and Aircraft Medical.

In October, St. Jude Medical completed its acquisition of Thoratec for $3.3 billion, expanding its heart failure business and adding products such as the HeartMate II left ventricular assist device. That same month, Cardinal Health completed its acquisition of Johnson and Johnson’s Cordis business for $1.944 billion.

TAVR in the spotlight

On Nov. 30, the Society of Thoracic Surgeons and the American College of Cardiology released data from its transcatheter aortic valve replacement (TAVR) registry that showed the increasing popularity of the procedure.

Between 2012 and 2014, the number of centers performing TAVR more than doubled from 156 to 348.

Meanwhile, marketing analytics firm GlobalData reported in March that the compound annual growth rate for TAVR valves will increase 19.7 percent between 2013 and 2020, expanding from $881 million to more than $3 billion over the period.

In late March, the FDA expanded the approval of the CoreValve device to include its use in valve-in-valve procedures in inoperable and high-risk patients.

In June, the FDA approved the CoreValve Evolut R, new-generation device for treating patients with severe aortic stenosis. That same month, the FDA approved the Sapien 3 as a treatment for high-risk patients with severe aortic stenosis.

In October, the FDA approved the Sapien XT transcatheter heart valve for aortic valve-in-valve procedures.

Other FDA approvals

As mentioned above, the FDA had a busy year even as it had a change in leadership. President Barack Obama nominated prominent cardiologist and researcher Robert Califf, MD, as the FDA commissioner on Sept. 15. The Senate must vote to confirm Califf’s appointment.

Here are some of the medications and devices the agency approved in 2015:

• The Watchman Left Atrial Appendage Closure Device, an option to long-term warfarin therapy for high-risk patients with nonvalvular atrial fibrillation.
• Sacubitril/valsartan, a twice-daily oral medication, to treat patients with heart failure and reduced ejection fraction.
• Ivabradine, an oral medication, to reduce the risk of hospitalization in patients with heart failure.
• The Synergy bioabsorbable polymer drug-eluting stent system to treat coronary artery disease. It is the first FDA-approved bioabsorbable polymer drug-eluting stent system.
• The Evera MRI Surescan ICD, the first ICD system for use with MRI scans. The Evera system is intended for patients with sudden cardiac arrest.
• Edoxaban, a factor Xa inhibitor, to reduce the risk of stroke in patients with nonvalvular atrial fibrillation and to treat deep vein thrombosis and pulmonary embolism after five to 10 days of initial therapy with a parenteral anticoagulant. Edoxaban is the fourth oral anticoagulant approved in recent years.
• The fixed dose combination of perindopril arginine and amlodipine to treat hypertension.
• The Impella RP System, a percutaneous single-access heart pump for patients who develop right heart failure or decompensation.
• The FlexAbility Ablation Catheter, which is used by electrophysiologists to treat arrhythmias.
• The Melody Transcatheter Pulmonary Valve, an artificial heart valve.
• The ENROUTE Transcarotid Neuroprotection System, which allows access to diseased carotid arteries through the neck rather than the femoral artery.
• The ResQCPR System, a dual-device cardiopulmonary resuscitation system designed to maximize the compression-decompression process and improve blood circulation to the heart and other organs.
• The Emblem subcutaneous implantable defibrillator (S-ICD) system, the second generation of the device.
• The Protégé GPS self-expanding peripheral stent system as a treatment for stenotic lesions of the common and external iliac arteries in patients with peripheral artery disease.
• The ProMRI Eluna, a pacemaker system that allows patients with single-chamber pacemakers to undergo full-body cardiac or thoracic MRI scans.
• The Impella 2.5 heart pump, which provides temporary ventricular support during high-risk PCIs.
• The 4 Fr 1.25 Solid Diamondback 360 Peripheral Orbital Atherectomy System to treat patients with peripheral artery disease.
• The Arctic Front Advance ST, cryoablation catheter for treating patients with paroxysmal atrial fibrillation.
• Cangrelor, an intravenous medication and antiplatelet drug, to prevent blood clots in adults undergoing PCI.
• The ViperWire Advance Peripheral Guide Wire with Flex Tip, a guide wire that is intended to reduce the tip stiffness while maintaining torque transfer for use in peripheral orbital atherectomy systems.
• The CorPath System for use during PCIs performed via radial access. 
• The combination of ambrisentan and tadalafil to reduce the risks of disease progression and hospitalization for worsening pulmonary arterial hypertension and improve exercise ability.
• Patiromer to treat patients with hyperkalemia, which typically occurs in patients with heart failure or kidney disease.
• The MyCareLink Smart Monitor, the first app-based remote monitoring system in the U.S. for patients with implantable pacemakers.
• The AngioJet ZelanteDVT thrombectomy catheter to treat patients with deep vein thrombosis.