ICD Benefits Hold Up for Modern-day Primary Prevention, but Questions Remain

Use of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death appears to be beneficial on the background of modern heart failure (HF) therapies, according to an analysis of real-world data, although there remains some question about the impact in the presence of all four pillars of guideline-directed medical therapy (GDMT).

Among patients with a primary prevention indication who were treated between 2012 and 2020, those who received an ICD had a 24.3% lower relative risk of all-cause mortality compared with those who didn’t receive an ICD. The results are consistent with the effect size seen in randomized trials, Aamir Ahmed, MD (University at Buffalo, NY), and colleagues report in a study published online last week in JACC: Clinical Electrophysiology.

ICD therapy “does provide significant mortality benefit in carefully selected patients who are deemed to be high risk for ventricular tachyarrhythmia and for a primary prevention indication,” Ahmed told TCTMD.

Relatively few study participants were taking the newest medications proven to have benefit in patients who have heart failure with reduced ejection fraction (HFrEF)—ie, angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors.

“The mechanisms of how ICD implantation and newer HF medications . . . work together to improve mortality should also be more closely analyzed in future studies,” Ahmed et al write.

Real-world Data

Prior trials establishing the efficacy of primary prevention ICDs for reducing sudden cardiac death in high-risk patients, including MADIT-II and SCD-HeFT, were completed roughly two decades ago, when HFrEF therapy mostly consisted of beta-blockers, ACE inhibitors/ARBs, and mineralocorticoid receptor antagonists (MRAs).

Since then, there have been advances in both medical and device therapy for patients with HFrEF, with SGLT2 inhibitors and ARNIs now joining those older therapies as essential parts of GDMT. With improved background therapies, there is some question about whether primary prevention ICDs carry the same benefits as were seen in the earlier trials.

To explore the question, Ahmed et al examined data from the Optum deidentified electronic health record data set, which includes information from more than 60 provider networks in the US. The analysis included 25,296 patients who had an indication for a primary prevention ICD between 2012 and 2020 and who survived at least a year from baseline; patients with cardiac resynchronization therapy (CRT) devices were excluded.

Overall, just 8.4% of patients had an ICD placed. Compared with other patients, ICD recipients were younger, were less likely to be female, and had greater use of HF medications at baseline. Of note, among all patients, fewer than 8% were on an ARNI and fewer than 3% were on an SGLT2 inhibitor at baseline. The investigators used propensity scores to match ICD recipients with other patients 1:4.

The lower risk of mortality observed in ICD-treated patients was observed over an average follow-up of about 2 years. The results were consistent across various subgroups.

At 5 years, all-cause mortality rates were 37.6% in the ICD group and 44.7% in the rest of the patients, a difference that worked out to a number needed to treat (NNT) of 14.1. That compares favorably, the researchers point out, with the NNTs in MADIT-II (10.0) and SCD-HeFT (13.7).

“One potential implication of having positive mortality benefits both in the prior HF medication studies and this study is that mortality improvements attributable to medical therapy work alongside mortality benefits with device therapy, with medications improving pump failure-related death and ICDs protecting against sudden cardiac death,” Ahmed et al write. “Given the importance of the contribution of guideline-directed medications and the continuing gaps in usage shown by this contemporary dataset, efforts are needed to improve adherence.”

Is This Really ‘Contemporary’ HF Therapy?

Mehmet Aktas, MD (University of Rochester, NY), commenting on the findings for TCTMD, called them “consistent with prior studies that have shown that an ICD continues to be beneficial in reducing mortality and reducing adverse outcomes.” He that the study also indicates underuse of ICDs among patients who might benefit from the therapy for primary prevention of sudden cardiac death.

Aktas has previously looked at the impact of ICDs among participants in the EMPEROR-Reduced trial of the SGLT2 inhibitor empagliflozin (Jardiance; Boehringer Ingelheim/Eli Lilly).

Zeroing in on the background HF therapy used in the current study, Aktas questioned whether this could truly be considered “contemporary” by the most up-to-date guidelines, especially since use of SGLT2 inhibitors and ARNIs was so low.

“We don’t know how an ICD performs if these drugs are fully implemented in a modern cohort . . . of heart failure patients,” Aktas said. “There are just no randomized studies that have that type of population included.”

A prospective study of patients who are on the four pillars of GDMT for heart failure and who are randomized to receive an ICD or not is what’s needed to definitively answer the question, Aktas said, noting that such a study would be difficult to perform since the indications for ICD implantation are already firmly established in guidelines.

But, he stressed, “unless we can create a study with a contemporary cohort with these treatments, with the novel treatments that are now available, it’s going to be very, very difficult to truly assess the impact of an ICD.”

For now, “I think there is a role for an ICD for sure,” Aktas said. “There’s ample data to show that among patients who continue to have LV dysfunction and who continue to have symptoms of heart failure, this is a population at very high risk for sudden cardiac death due to ventricular arrhythmias.”