Early, Large LDL Reduction Tied to Lowest Event Rates After MI

Debra L. Beck

January 07, 2021

In registry data covering more than 40,000 patients with myocardial infarction (MI) followed for almost 4 years, those with the largest early reductions in LDL-C appeared to reap the greatest reductions in adverse cardiovascular (CV) events, including death.

Between the index event and a 6- to 10-week follow-up visit, patients who were in the 75th percentile for LDL-C reductions (an absolute reduction of 1.85 mmol/L or 71.5 mg/dL), compared with those in the 25th percentile (0.36 mmol/L or 14 mg/dL), had a 32% reduction in CV death and a 23% reduced risk for the composite of CV death, MI, and ischemic stroke.

Additionally, MI was 29% lower and ischemic stroke 24% lower (P < .05 for both), while all-cause death was reduced 29%, heart failure hospitalization 27%, and coronary artery revascularization 14% (P < .05 for all).

Between the index event and the follow-up visit for cardiac rehabilitation scheduled for 6 to 10 weeks after discharge, only 10,995 patients (or 27%) had an LDL-C reduction of 50% or more.

"A 50% reduction in LDL is an important goal, but some patients will have a hard time reaching that goal and our data show that early use of high-intensity statin treatment appears to be beneficial in and of itself," said first author Jessica Schubert, MD, a clinical pharmacologist from Uppsala University, Sweden.

Schubert and colleagues published their findings online December 24 in the European Heart Journal.

Go High to Go Low

In a comparison of those who did and did not achieve a 50% LDL-C reduction after receiving high-intensity statin therapy, the event curves in favor of a greater reduction in LDL-C started to separate at about 4 months.

Even in patients who did not achieve a reduction in LDL of at least 50%, those prescribed high-intensity statins had more favorable event curves than those who took medium-intensity statins, noted Schubert.

"It was interesting to see such an early difference in event rates or major adverse cardiac events — comparing high, low, or medium intensity statins — but it just strengthens the message for early, aggressive lowering," said Schubert, a clinical pharmacologist.

"Unfortunately, we have too many studies that continue to document a significant treatment gap, with underuse of high-intensity statin therapy," Nihar R. Desai, MD, MPH, told theheart.org | Medscape Cardiology. He added that there also needs to be more focus on adherence and persistence to high-intensity statin therapy.

"There is a conspicuous gap between what clinical evidence and clinical guidelines would suggest we do and what we actually do in clinical practice. In parallel, there is a great need to engage with patients, caregivers, and communities and dispel some of the many myths surrounding statin therapy," he added.

Desai is an investigator at the Center for Outcomes Research and Evaluation at Yale School of Medicine and was not involved in this study.

Numerous randomized trials have shown that lowering LDL-C after MI reduces the risk for recurrent events. Indeed, LDL lowering is a cornerstone of secondary prevention of cardiovascular disease, but there is actually little evidence in real-world settings looking at the impact of early changes in LDL-C or the intensity of statin therapy after a MI and long-term prognosis.

"There are many trials on this, but actually very few large observational studies, and none that compliment baseline LDL levels with LDL levels at early follow-up like we have, and then a long-term follow-up on top of that," said Schubert.

Schubert and colleagues used data from SWEDEHEART, a Swedish nationwide MI quality registry that includes all patients between the ages of 30 and 75 years admitted with an MI to any of the 74 coronary care units in Sweden. For those hospitalized more than once during the study period, only the first hospitalization was considered.

The relatively young age of participants in SWEDEHEART is an acknowledged limitation of the data. In an interview, Schubert explained: "Here in Sweden, at the time of the study, only patients younger than 75 years were followed-up at the hospital cardiology clinic and the rest were followed-up in primary care, so we don't have details on them. So, for example, we have not studied if a 90-year-old has an MI, if they are even prescribed a statin."

More recently, Sweden has moved up this age restriction and started following all patients younger than 80 years in the cardiology clinic, sending older people to primary care follow-up.

Desai doesn't feel like the mean age of the studied population is really much of a limitation. "It is reflective of contemporary practice and quite consistent with the population enrolled in the clinical trials," he said.

Among the 40,607 patients followed for a median of 3.78 years, the median LDL-C at the time of the index event was 3.1 mmol/L (120 mg/dL) and the median change in LDL-C was –1.20 mmol/L (–46 mg/dL).

Just over three-quarters of participants (77%) were statin-naïve at the time of the index event, and only 3% of patients were discharged without a statin, said Schubert.

The study was partially funded by the Swedish Heart and Lung Foundation and by a grant from Amgen. Schubert reported receiving grants from Amgen during the conduct of the study. Desai reports being a consultant and receiving research grants from Amgen, Astra Zeneca, Boehringer Ingelheim, Cytokinetics, Myokardia, Novartis, Relypsa, and SC Pharmaceuticals.

Eur Heart J. Published online December 24, 2020. Full text

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