For decades, we’ve been giving an aspirin to every patient suspected of having acute coronary syndrome (ACS) who enters the emergency department. The ISIS-2 trial published in The Lancet in August 1988 (“Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial Infarction”) concluded that, of patients ultimately having an ST elevation myocardial infarction 9STEMI), the number needed to treat (NNT) to prevent one death at 30 days was 42. The death rate went from 11.8 percent to 9.4 percent.

However, there are a couple things to consider about ISIS-2: First, chest pain patients with a STEMI represent a very small fraction of the suspected ACS patients presenting to the emergency department. Second, the death rate from STEMI is now about 5 percent, much lower than in 1988. Despite these two factors that would substantially mitigate the efficacy of aspirin in chest pain patients, we still give it to everyone who has chest pain suspected to be ACS.

Nobody argues with giving aspirin even when the vast majority who get it will likely receive no benefit. One aspirin may help a very small percentage of suspected ACS patients and isn’t going to hurt anyone—a no-brainer.

In many ways, however, the case for giving high-dose statins to potential ACS patients may be potentially stronger than that for aspirin.

Statins have long been known to have other effects besides lowering LDL cholesterol. These pleiotropic effects include decreasing platelet adhesion, inhibiting thrombosis, improving endothelial function, decreasing inflammation, and stabilizing plaque. The fundamental question is whether these pleiotropic effects (and others that may be unknown) can acutely benefit ACS patients.

Unfortunately, as of yet, there is no study that hits the nail directly on the head regarding the benefits of statins given in the emergency department, but there are many that suggest that there may be a benefit.

THE CASE FOR EARLY STATINS

Below are some studies that indirectly support the idea that statins should be given to every suspected ACS patient in the emergency department. Unfortunately, as of yet, there is no study that hits the nail directly on the head regarding the benefits of statins given in the emergency department, but there are many that suggest that there may be a benefit.

Saab FA, Eagle KA, Kline-Rogers E, et al. COMPARISON OF OUTCOMES IN ACUTE CORONARY SYNDROME IN PATIENTS RECEIVING STATINS WITHIN 24 HOURS OF ONSET VERSUS AT LATER TIMES. Am J Cardiol. 2004;94(9):1166-1168.

This large study by Saab et al looked at 1,639 statin-naive ACS patients who received statins within 24 hours of admission and found that inpatient mortality wasn’t significantly lower (1.64 percent versus 2.26 percent) compared with those who received them later than 24 hours after admission. There were, however, substantial differences in other outcomes:

• Inpatient pulmonary edema (6.9 percent versus 15.8 percent; NNT = 11)
• Cardiogenic shock (2.2 percent versus 7.3 percent; NNT = 20)
• Atrial flutter or fibrillation (5.2 percent versus 9.0 percent; NNT = 21)
• Major bleeding (4.9 percent versus 10.4 percent; NNT = 18)
• The composite outcome of death-reinfarction-stroke (7.0 percent versus 10.4 percent; NNT = 29)
• The six-month composite outcome of death-myocardial infarction (MI)-stroke-rehospitalization (32.8 percent versus 38.3 percent; NNT = 18)

Ferrières J, Cambou JP, Guéret P, et al. EFFECT OF EARLY INITIATION OF STATINS ON SURVIVAL IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (THE USIC 2000 REGISTRY). Am J Cardiol. 2005;95(4):486-489.

In a nonrandomized registry study of 2,210 acute myocardial infarction (AMI) statin-naive patients receiving statins within 48 hours of admission, there was a hazard ratio of 0.57 for a one-year prognosis for cardiovascular deaths and/or recurrent MIs.

Lenderink T, Boersma, E, Gitt AK, et al. PATIENTS USING STATIN TREATMENT WITHIN 24 HOURS AFTER ADMISSION FOR ST-ELEVATION ACUTE CORONARY SYNDROMES HAD LOWER MORTALITY THAN NON-USERS: A REPORT FROM THE FIRST EURO HEART SURVEY ON ACUTE CORONARY SYNDROMES. Eur Hear J. 2006;27(15):1799-1804.

There isn’t much I can add here—just reading the title gives you the results.

Fonarow GC, Wright RS, Spencer FA, et al. EFFECT OF STATIN USE WITHIN THE FIRST 24 HOURS OF ADMISSION FOR ACUTE MYOCARDIAL INFARCTION ON EARLY MORBIDITY AND MORTALITY. Am J Cardiol. 2005;96(5):611-616.

This registry analysis (174,635 AMI patients from 1,230 hospitals) found numbers that were too good to be true. Patients started on early statins had an in-hospital mortality of 4 percent; the rate was 5.3 percent in patients already taking them and 15.4 percent in those not treated with statins. Although I’m trying to make the case for early statins, even I can’t believe the results of this study.

The problem with all of these studies is that none of them indicated that statins were given in the emergency department. Statins within 24 hours and within 48 hours were beneficial. It would seem that the earlier they are given, the better, but we don’t know for sure.

What about randomized controlled trials? A meta-analysis of 12 trials involving more than 13,000 patients concluded, “Early statin therapy in ACS patients had no statistical effect on virtually any of multiple outcome measures, including the primary combined endpoint.” But what’s early? Studies looking at initiation of statins at seven to 14 days are irrelevant to our question.

EARLY STATINS AND PCI

Not convinced yet? Here’s more positive news about the value of early statins. It focuses on their use in patients having a percutaneous coronary intervention (PCI).

Chan AW, Bhatt DL, Chew DP, et al. EARLY AND SUSTAINED SURVIVAL BENEFIT ASSOCIATED WITH STATIN THERAPY AT THE TIME OF PERCUTANEOUS CORONARY INTERVENTION. Circulation. 2002;105(6):691-696.

The Chan et al study included 5,052 patients not having ACS who had a PCI. About a thousand were treated with a statin at the time of their PCI and had greater comorbidities. Statin therapy was associated with a mortality reduction at 30 days (0.8 percent versus 1.5 percent; hazard ratio, 0.53; P = 0.048) and at six months (2.4 percent versus 3.6 percent; hazard ratio, 0.67; P = 0.046). And these patients weren’t even having MIs. (PCIs have been known to bump troponins by 5 to 40 percent [periprocedural MIs], suggesting that some leakage occurs during the process even in elective PCIs.)

Patti G, Pasceri V, Colonna G, et al. ATORVASTATIN PRETREATMENT IMPROVES OUTCOMES IN PATIENTS WITH ACUTE CORONARY SYNDROMES UNDERGOING EARLY PERCUTANEOUS INTERVENTION: RESULTS OF THE ARMYDA-ACS RANDOMIZED TRIAL. J Am Coll Cardiol. 2007;49(12):1272-1278.

Here’s another provocative paper where the title tells the tale. This was a randomized controlled trial of 171 patients demonstrating that non-STEMI (NSTEMI) patients getting high-dose atorvastatin (80 mg) 12 hours prior to a PCI had a decrease in the 30-day composite outcome of death, MI, or unplanned revascularization (5 percent versus 17 percent, mostly due to a reduction in MIs [5 percent versus 15 percent]).

Benjo AM, El-Hayek GE, Messerli F, et al. HIGH DOSE STATIN LOADING PRIOR TO PERCUTANEOUS CORONARY INTERVENTION DECREASES CARDIOVASCULAR EVENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. Cath Cardiovasc Interv. 2015;85(1):53-60.

Finally, here’s a meta-analysis of 14 studies of statin-naive patients with stable angina, NSTEMIs, or mixed indications. Curiously, STEMIs weren’t included because it was felt that the short time between drug administration in the emergency department and the PCI would be insufficient to note a drug effect—just the effect we’re looking for!

Only one of the studies was ED-based and involved only 171 patients, comparing 80 mg versus 10 mg of atorvastatin. The ED study had an extraordinarily low rate of major adverse cardiac events, and so the difference between high- and low-dose statins didn’t achieve statistical significance. However, the rate was substantially lower in the high-dose statin group (5.8 percent versus 10.6 percent). It’s hard to conceive that such an underpowered study would be performed. But it suggests that high-dose statins are beneficial (and this perhaps could have been proven if the study was adequately powered).

Here’s the result of the meta-analysis: Statin loading was associated with a reduction in the combined endpoint of death, spontaneous MI, and target vessel revascularization (odds ratio, 0.59; 95 percent CI, 0.38–0.92, P = 0.02), but this benefit was observed only in the subgroup of patients undergoing PCI for NSTE-ACS (odds ratio, 0.18; P = 0.0005).

Well, isn’t an NSTEMI an AMI? Even though there are prior studies suggesting value of statin loading in non-AMI patients, I’m happy with the conclusion of this paper. Although often a trap, a pathophysiologic argument would suggest that if statins work in NSTEMIs, why would they not work in STEMIs?

So here are the options: Wait 10 years for the definitive randomized controlled trial demonstrating that all suspected ACS patients be given a single high-dose statin in the emergency department and potentially allow 10 years’ worth of patients to receive no benefit, or begin now based on the evidence presented above. No one will be hurt if you do give a single dose of statins—some ACS patients will likely be helped.

So be courageous and take this article to the cardiology committee at your hospital and tell them that you want to do this. Like giving aspirin, it’s also a no-brainer.

Dr. Bukata is the executive editor of Emergency Medical Abstracts and a clinical professor of emergency medicine at the Keck School of Medicine of USC in Los Angeles.