The Risk of Withdrawing Statins

Summarized by Robert W. Griffith, MD
April 23, 2002 (Reviewed: April 5, 2004)

Introduction

It's now accepted that the benefits of the HMG-CoA reductase inhibitors (statins) are not entirely due to their cholesterol-lowering effects; they also have local and systemic anti-inflammatory activity that is relevant for the progression of atherosclerosis. This may be due to their action in releasing endothelial nitric oxide. Statin therapy produces a marked reduction in coronary events in patients with coronary disease, which goes beyond that associated with a reduction in LDL cholesterol levels. Studies suggest that withdrawal of statin treatment leads to impaired nitric oxide bioavailability and may possibly be associated with an increased tendency to thrombotic events. Now a publication in Circulation reports on the result of withdrawal of statins in people with acute coronary syndromes.

Method

Data were analyzed from the Platelet Receptor Inhibition Syndrome Management (PRISM) study that was done in coronary artery disease patients with chest pain at rest or accelerating chest pain in the previous 24 hours. Patients were given aspirin before being randomized to receive either tirofiban (a platelet aggregation inhibitor) or heparin. End-points included in the study were death and non-fatal myocardial infarction (MI), at 48 hours, 7 days and 30 days.

PRISM patients with complete medical records, including statin treatment particulars, were used for this analysis. There were 1,616 such patients (808 on heparin, 808 on tirofiban). The impact of statin therapy on patient outcome was evaluated using a Cox proportional hazard model.

Results

Among the 1,616 patients there were 47 deaths and 65 non-fatal MIs during the 30-day follow-up period. At baseline, there were 1,249 patients not taking statins, 379 patients who were taking statins and stayed on them after hospitalization, and 86 who discontinued after hospitalization. Most of those on statins took simvastatin (50%), followed by lovastatin (24%) pravastatin (20%), and fluvastatin (5%); their cholesterol levels were about 10% lower than those not on statins.

For those patients who continued on statins after hospitalization, the 30-day event rate (death or MI) was significantly reduced compared with those patients who didn't take statins -- the hazards ratio was 0.49 (95% confidence interval [CI], 0.21 to 0.86, p=0.004).

For those who discontinued statin therapy, the 30-day event rate was increased compared with those who continued on statins; the hazards ratio was 2.93 (95% CI, 1.64 to 6.27, p=0.005). Moreover, the rate tended to be higher (though not statistically significantly) than in those patients who never took statins -- hazard ratio = 1.69 (95% CI, 0.92 to3.56, p=0.15).

There were 165 patients who started on statins during their hospitalization. They had a trend to reduced death and MI rates during the 30-day period, compared with those who didn't take statins, though this was not statistically significant; hazard ratio = 0.76 (95% CI, 0.51 to 1.35, p=0.22).

Curves for the occurrence of cardiac events for the 'discontinuers' versus the other two groups (no statins and continued statins) diverged in the first 3 days after baseline. Total cholesterol levels showed no changes over the first 3 days in these three groups. On the other hand, serum troponin T levels (measured as a marker of cardiac muscle damage) and ST changes on EKG during the first 3 days were increased significantly in the 'discontinuers'.

Conclusions

This analysis shows that ongoing statin treatment in patients presenting with acute coronary syndromes (pain at rest, or accelerating pain) is associated with improved outcomes -- fewer deaths and MIs -- in the next few days. On the other hand, discontinuation of statin therapy after the onset of symptoms has the opposite effect -- a three-fold increase in the number of cardiac events throughout the next 30 days.

The findings indicate that statins produce beneficial effects independent of their lipid-lowering actions. Abrupt withdrawal of statins may indeed reverse the up-regulation of endothelial nitric oxide synthase, with a subsequent increase in thrombotic tendencies. Whatever the possible mechanism, however, the lesson is clear; as the authors of the study say, "withdrawal of statin therapy in unstable patients should be avoided".

Source

• Withdrawal of statins increases event rates in patients with acute coronary syndromes. C. Heeschen, CW. Hamm, U. Laufs,  et al., Circulation, 2002, vol. 105, pp. 1446--1452

Related Links
Statins for the Older-Old
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