Long-Term Outcomes With Higher Initial Statin Dose in Myocardial Infarction

Better long-term cardiovascular outcomes are dose-dependently associated with higher initial statin dose following myocardial infarction (MI), according to findings published in the European Heart Journal Cardiovascular Pharmacotherapy.

Investigators sought to determine the real-life long-term impact of the initial statin dose following MI. The study’s primary outcome was major adverse cardiovascular or cerebrovascular events (MACCE) within 10 years.

The retrospective population-based study gathered information from Finnish national registries on 72,401 consecutive adult patients with MI (mean age, 68 years; 67% men) admitted from July 2004 through June 2018 and treated with statins soon after the MI event. Investigators identified patients from the Care Register for Healthcare in Finland which includes data from all 20 Finnish hospitals that treat patients with MI. They included only the first MI admission during the study period.

Patients treated with aortic or valvular surgery during the index admission, those who used a PCSK9 inhibitor, and those with missing follow-up data were excluded.

Multivariable regression was used to adjust for differences in revascularization, comorbidities, baseline features, and usage of additional evidence-based medications.

There was initial statin therapy (defined as medication purchase by prescription within 90 days following hospital discharge) in the study population (high-dose 26.3%, moderate-dose 69.2%, low-dose 4.5%) with median follow-up of 4.9 years. Statin therapy adherence was studied by yearly intervals during follow-up. There was an inverse relationship between therapy intensity decreasing and increasing age.

The most frequently used initial statin overall was simvastatin, and the most frequently used high-dose statin was atorvastatin. Patients with the fewest comorbidities most frequently were prescribed high-dose statin. Patients with the highest comorbidities most frequently were prescribed low-dose statin.

High-dose vs moderate-dose statin showed MACCE was less frequent (adjusted hazard ratio [aHR], 0.92; P <.0001; number needed to treat [NNT], 34.1). MACCE was less frequent in high-dose vs low-dose (aHR, 0.81; P <.001; NNT, 13.4) and in moderate-dose vs low-dose (aHR, 0.88; P <.0001; NNT, 23.4). Lower initial statin dose associated with atrial fibrillation and usage of oral anticoagulation.

High-dose vs moderate-dose revealed a lower frequency of stroke (a_{subdistribution[s]}HR, 0.86; P <.0001), recurrent MI (a_sHR, 0.91; P =.0001), and death (aHR, 0.87; P <.0001; NNT, 23.6).

Subgroups divided by sex, dementia, heart failure, atrial fibrillation, diabetes, revascularization, prior statin usage, usage of other evidence-based medications, or age all showed higher initial statin dose after MI was associated with better long-term outcomes. Statin therapy adherence decreased during follow-up (24.1% of all patients were noted as nonadherent 10 years after index MI). At 10 years, dosage of used statins was similar to initial dosage (high-dose 27.7%, moderate-dose 68.3%, low-dose 4.0%).

Study limitations include the retrospective design and residual confounding. Dosing instructions are also assumed by investigators and are not objective.

“…a higher initial statin dose after MI is dose-dependently associated with better long-term cardiovascular outcomes,” the investigators wrote. “Paradoxically, however, patients with the highest risk for adverse outcomes used the lowest intensity of statins.” They urged the significance of using high-dose statins soon after MI.