New drugs, policy, controversy, and all the big trials of 2019
The year in cardiology started out with a scramble to understand the December 2018 meta-analysis that showed a near doubling in mortality with paclitaxel devices for peripheral artery disease (PAD).
The FDA announced it was looking into the safety signal in January and released a safety advisory about it in March calling for physicians to consider alternatives.
Industry and professional groups started rapidly pulling together and optimizing all the data they could from the clinical trials.
Manufacturers argued that their patient-level data suggest no significant mortality disadvantage with the balloons or stents nor a paclitaxel dose-mortality relationship after correcting for crossover and taking into account registry data.
Discussions at the VIVA Physicians and Cardiovascular Research Technologies meetings showed a high level of skepticism among clinicians that the signal could be real.
However, in June, the FDA affirmed that the longer-term mortality signal was still there in the data it collected from industry.
"We're being subjected to a forest of dueling numbers," lamented John Hirshfeld, MD, of Penn Heart and Vascular Center in Philadelphia. The advisory committee he was on ultimately recommended against withdrawal of paclitaxel PAD devices from the market, citing short-term benefit.
The dueling numbers didn't stop there. While the most comprehensive patient-level data from the trials still showed an excess risk, the magnitude dropped to only 27% elevated risk in data presented in September at the Transcatheter Cardiovascular Therapeutics meeting. Pooled 5-year data from the LEVANT trials of a paclitaxel-coated balloon at the same meeting suggested no increased risk.
A potential mechanism has still not been found. Real-world data is seen as the next step.
A Good Year for CAD
In coronary artery disease, the year held much more positive news.
The REDUCE-IT trial made icosapent ethyl (Vascepa) the belle of the ball at the American Heart Association meeting late in 2018, with demonstration of 25% relative reduction of cardiovascular events, and the party continued through 2019.
In July, the Institute for Clinical and Economic Review called the prescription fish oil product cost-effective as an add-on to standard therapies for cardiovascular disease event prevention.
In November, an FDA advisory committee unanimously recommended an expanded indication for cardiovascular risk reduction.
Another lipid-lowering agent got expanded approval for hard endpoints in April: PCSK9 inhibitor alirocumab (Praluent) scored an indication for cardiovascular secondary prevention to put it on par with evolocumab (Repatha).
For primary prevention, guidelines were updated in March that most notably downgraded aspirin while boosting heart-beneficial diabetes medications.
Real controversy, though, came from a dietary guideline saying red and processed meats doesn't adversely affect health.
Perhaps the biggest development in CAD for 2019 was release of the ISCHEMIA trial findings, a decade in the making.
The trial, billed as a successor to the seminal COURAGE trial, found early revascularization wasn't better than optimal medical management alone in stable CAD outside the left main.
With neutral findings, cardiologists saw whatever they wanted and little real change in practice was predicted.
COMPLETE, though, handed early complete revascularization a win for hard outcomes over percutaneous coronary intervention (PCI) on only the culprit lesion in ST-segment myocardial infarction (MI), although it didn't appear to matter whether staged or immediate.
In TWILIGHT, dropping aspirin early after stenting was safer for high-risk stent recipients on a ticagrelor (Brilinta)-based antiplatelet regimen.
On the policy front, the Centers for Medicare & Medicaid Services announced it would start covering PCI in ambulatory surgery centers starting in 2020. Hospitals weren't happy.
Novel drugs with positive pivotal trial results this year that could presage new options in the clinic included inclisiran, a twice-yearly injection that blocks PCSK9 via small interfering RNA. ORION trials showed the drug halves LDL levels atop other lipid-lowering drugs.
The novel monoclonal antibody evinacumab had nearly the same effect in homozygous familial hypercholesterolemia, even atop a PCSK9 inhibitor.
More modest effects were seen with novel small-molecule oral agent bempedoic acid in its final pivotal trials.
Older drug colchicine also could have a future beyond gout treatment, as it scored for secondary prevention after MI in the COLCOT trial.
Read the original article on Medpage Today: Year in Review: Coronary and Peripheral Artery Disease