SMART-CHOICE and STOPDAPT-2
These two large multicenter studies demonstrate that DAPT can safely be stopped early if needed. SMART-CHOICE from South Korea and STOPDAPT-2 from Japan each randomized roughly 3,000 patients undergoing PCI to 12 months of DAPT or to DAPT for only 3 months or 1 month, respectively, at which point the aspirin was dropped and patients in the abbreviated DAPT arm continued on P2Y12 inhibitor monotherapy, mostly clopidogrel, for the remainder of the 12 months. In the Japanese STOPDAPT-2 trial, 1 month of DAPT proved superior to 12 months of DAPT for the primary composite endpoint of cardiovascular death, MI, stroke, definite stent thrombosis, or major or minor bleeding at 12 months (7). In the South Korean SMART-CHOICE trial, 3 months of DAPT was noninferior to 12 months for major adverse cardiac and cerebrovascular events, and superior in terms of bleeding risk ( ). Of note, roughly half of patients in the two trials were lower-risk individuals undergoing PCI for stable angina.
Dr. Bell noted that, while the TWILIGHT trial (Ticagrelor With or Without Aspirin in High-Risk Patients After PCI) didn’t make his top-five list, it certainly fits well with the two East Asian studies. The TWILIGHT investigators randomized more than 7,000 patients to 12 months of DAPT or discontinuation of aspirin after 3 months. The result: a lower incidence of clinically relevant bleeding with ticagrelor monotherapy, and with no increased risk of death, MI, or stroke, compared with 12 months of DAPT).
“Again, I would just question what the added value of aspirin is here,” Dr. Bell commented. “Many interventional cardiologists are absolutely terrified of their patients having stent thrombosis, but with second-generation drug-eluting stents – the stents we’re putting in day in and day out – the risk of stent thrombosis is less than 1%. And in these two trials it was less than 0.5%. There’s more risk of having major bleeding events than there is of ischemia, so I think the balance is in favor of preventing bleeding. We know that major bleeding predicts short- and long-term mortality.”
This double-blind trial randomized 4,745 patients within 30 days post MI to low-dose colchicine or placebo on top of excellent rates of background guideline-directed medical therapy. The goal was to see if this anti-inflammatory agent could reduce cardiovascular events independent of any lipid-lowering effect, as was earlier seen with canakinumab in the CANTOS trial. It did so to a statistically significant but relatively modest degree, with a 5.5% rate of the composite cardiovascular events endpoint in the colchicine group and 7.1% in placebo-treated controls (). But Dr. Bell was unimpressed.
“All-cause mortality was identical at 1.8% in both groups. So colchicine is not saving lives. In fact, the only real differences were in stroke – but the study wasn’t powered to look at stroke – and in urgent hospitalization for angina leading to revascularization, which is a soft endpoint,” he observed.
Plus, 2.5% of patients were lost to follow-up, which Dr. Bell considers “a little concerning” in a trial conducted in the current era.
“In my opinion, the evidence that colchicine is effective is weak, and I don’t think really supports the drug’s routine use post MI. We already send these patients out on numerous medications. We have to think about cost/benefit, and if a patient asks me: ‘Is this going to prevent another heart attack or make me live longer?’ I think the unequivocal answer is no,” he said.
These days colchicine is no longer an inexpensive drug, either, at an average cost of $300-$400 per month, the cardiologist added.