Statins cut peripheral artery disease mortality, even when started long after diagnosis

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Statins are linked with reduced mortality in patients with peripheral arterial disease (PAD), even when started late after diagnosis, reports a study presented at ESC Congress 2019 together with the World Congress of Cardiology. Patients who stop the drug are at similar risk to those who never start. The research shows the importance of starting and adhering to lifelong medication, preferably at a high dose.

Around 200m people worldwide have PAD, a condition in which arteries in the legs are clogged. This restricts blood flow to the legs and raises the chances of stroke and heart attack. Around 30% of patients have pain and cramping in their legs when they walk – referred to as intermittent claudication – while others have gangrene in the feet due to poor circulation.

Statins are recommended for all patients with PAD, together with smoking cessation, exercise, healthy diet, and weight loss Statins diminish the risk of stroke and heart attack by reducing low-density lipoprotein (LDL) cholesterol, which causes blocked arteries (atherosclerosis).

But adherence to statins is low: over the past five years, just 57% of patients in Europe took the medication as directed. In 2016 to 2017, only one-third of patients on statins reached the LDL cholesterol target of below 1.8 mmol/L (70 mg/ dl).(3)

This study examined whether adherence to statin therapy influenced survival in patients with symptomatic PAD. The study enrolled 691 patients admitted to hospital between 2010 and 2017 and followed-up for a median of 50 months.

At the beginning of the study, 73% of patients were on statins, increasing to 81% at the 50-month follow-up. The dose of drug also increased between the two time periods, which was paralleled by a significant drop in LDL cholesterol from 97 to 82 mg/dL. Patients who stopped taking a statin had a similar mortality rate (33%) to those who never took the drug (34%). Adhering to statins throughout the 50 months was linked with a 20% rate of death.

Taking high-dose statins throughout the study was linked with the lowest mortality rate (10%), while reducing the dosage during the study was related to the highest death rate (43%).

Study author Dr Jörn Dopheide of Bern University Hospital, Switzerland said: “The study shows that adherence to statins is essential for the best prognosis. We also show that it is never too late to start medication and benefit from it. On top of that, it is crucial not to reduce the dose because LDL cholesterol levels rise again, thus increasing the overall risk on top of the residual risk for further events.”

He concluded: “All PAD patients should take statins, preferably very potent statins, like rosuvastatin 40 mg or atorvastatin 80 mg, or at the highest tolerable dose. In the rare case of statin intolerance, which was around 2% in our study, alternative lipid lowering therapies must be considered.

Abstract
Background: Statins reduce cardiovascular morbidity and mortality, but adherence is suboptimal. We hypothesized that adherence to statin therapy determines survival in a population at very high cardiovascular risk.
Methods: Single center observational study with 691 symptomatic PAD patients admitted to a tertiary university center between 2010 and 2017. Outcome was evaluated over a mean follow-up of 50±26 months. We related statin adherence and LDL-C target attainment to total mortality.
Results: At the first contact, 73 % of our PAD patients were on statins with a significant increase in statin use to 81 % (p<0.0001) at follow-up: Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/ day (p<0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/ dL (p<0.0001). The proportion of patients receiving a high intensity statin increased over time from 38 to 62 % (p<0.0001). Percent LDL-C decrease over time was highest in patients with high intensity statin treatment, followed by moderate, low intensity or non-statin treatment, respectively (p=0.01).

Patients never receiving statins had a higher mortality rate (34%) as compared to patients being on statins (20%) or having newly received a statin (15%; p < 0.01). Moreover, patients on intensified statin medication had the lowest mortality (10%), whereas patients who terminated statin medication or reduced the statin dosage had a higher mortality rate (33% and 43%, respectively; p < 0.05).
Conclusion: Our data prove that statin treatment, particularly high-intensity therapy, reduces mortality in symptomatic PAD. In terms of mortality, patients benefit even from de novo statin therapy (“it is never too late”), whereas dose reduction or statin discontinuation have deleterious effects. A strategy of intensive and sustained statin therapy is worthwhile.

Authors
J F Dopheide, H Ramadani, J Veit, L Adam, L Papac, M Schindewolf, A Vonbank, I Baumgartner, H Drexel

European Society of Cardiology material ESC 2019 abstract

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