Case 2:

Pinto et al performed the analysis, the largest to date, comparing onsite fibrinolysis and pPCI in STEMI patients [3]. The analysis included data on consecutive patients gathered in National Registry of Myocardial Infarction from June 1994 do December 2006.

The aim of the study was to evaluate the effect of delays to reperfusion on the comparative efficacy of pPCI and onsite fibrinolysis (FT).

Propensity matching of patients treated with pPCI and onsite fibrinolysis was performed. The matched study population comprised n=9506 pPCI patients and n=9506 onsite fibrinolysis patients from 580 and 733 hospitals, respectively. Three subgroups were specified on the basis of PCI-related delay time (defined as door-to-balloon time – door-to-needle time): 1) <60 minutes, 2) 61-90 minutes, 3) >90 minutes. Analyzed clinical outcomes involved death; death or MI; death, MI or stroke.

In any of the analyzed subgroups, pPCI was associated with worse outcomes compared with onsite fibrinolysis. However, as multivariable analysis demonstrated, the survival benefit of pPCI over onsite fibrinolysis was lost after ≈ 120 minutes of PCI-related delay.

The study emphasis, in line with international recommendations, that creating one protocol for all STEMI patients is impossible. Transport times, patient characteristics, local hospital experience should be taken into consideration and be the basis to choose the best treatment strategy.

[1] William Wijns, Philippe Kolh et al. Guidelines on myocardial revascularization. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association for Percutaneous Cardiovascular Interventions (EAPCI). European Heart Journal (2010) 31, 2501–2555

[2] Antman EM et al. 2007 Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee. Circulation 2008; 117: 296 –329
[3] Duane S.Pinto et al. Benefit of Transferring ST-Segment–Elevation Myocardial Infarction Patients for Percutaneous Coronary Intervention Compared With Administration of Onsite Fibrinolytic Declines as Delays Increase. Circulation 2011, 124: 2512-2521

Nicholls and colleagues conducted a prospective randomized multicentre, double-blind trial – the SATURN trial (The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin versus Atorvastatin) which results have been recently published in NEJM [4].

The study compared two intensive statin regimens with atorvastatin and rosuvastatin on coronary atherosclerosis regression and cardiovascular event rates and safety profile.

The study population consisted of 1039 patients, n=519 in atorvastatin group and n=520 patients in rosuvastatin group. Both statin-naive and on-statin treatment patients were enrolled. Participants aged 18-75 years, with at least one vessel with 20% stenosis on clinically indicated coronary angiography and a target vessel for imaging with <50% stenosis were included in the trial. Exclusion criteria involved intensive lipid-lowering therapy for >3 months in the previous year, uncontrolled hypertension, heart failure, renal dysfunction or liver disease. LDL-levels at entry were >100 mg/dl for patients not treated with a statin in the preceding 4 weeks and >80 mg/dl for those already on statins.

Patients were initially administered either a dose of 40 mg daily atovastatin or 20 mg daily rosuvastatin for 2 weeks. Thereafter the whole study population underwent second randomization to full-dose treatment with atorvastatin (80 mg/d) or rosuvastatin (40 mg/d) for 104 weeks.

To asses the regression of atherosclerosis, IVUS was performed at baseline and after 104 weeks.

The primary efficacy end point was percent atheroma volume (PAV) and the secondary efficacy end point was normalized total atheroma volume (TAV).

There were no significant differences in demographic characteristics or in baseline medication use or laboratory results between the two study groups.

The outcomes of the study have shown that both statin regimens were similar in reducing atherosclerotic plaque; both limited progression or induced regression of coronary disease.

There was no significant difference between 2 groups regarding the primary end point, atorvastatin decreased PAV by 0.99% (95% CI, -1.19 to -0.63) and rosuvastatin decreased PAV by 1.22% (95% CI, -1.52 to –0.90) (p=0.17). Significant deifference was observed in regard to TAV, for rosuvastatin: -6.39 mm (95% CI, -7.52 to -5.12) as compared with atorvastatin: -4.42 mm (95% CI, -5.98 to -3.26) (p=0.01). In two thirds of the patients in both groups was obtained regression of atherosclerosis: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (p=0.07) and 64.7% and 71.3%, respectively, for TAV (p=0.02). LDL and HDL levels were decreased with significant difference between two regimens, achieving levels recommended by international guidelines. LDL levels with rosuvastatin vs atorvastatin at 104 weeks were 62.6 vs 70.2 mg/dl, p<0.001 and HDL levels: 50.4 vs 48.6 mg/dl, p=0.01.

Despite maximum statin doses, side effects were not frequent. The rate of cardiovascular events was similar in both groups. Significant difference concerned ALT levels: 2.0% with atorvastatin vs 0.7% with rosuvastatin (p=0.04) and proteinuria: 3.8% with rosuvastatin vs 1.7% with atorvastatin (p=0.02). Neither treatment increased glycated hemoglobin levels, what has been raised recently.

In conclusion, SATURN trial proved efficacy and safety of very intensive lipid-lowering therapy.

[1] Zeljko Reiner, Alberico L. Catapano et al. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Developed with the special contribution of: European Association for Cardiovascular Prevention & Rehabilitation. European Heart Journal (2011) 32, 1769–1818

[2] Van De Werf F et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. European Heart Journal 2008;

29:2909–2945

[3] Christian W. Hamm, Jean-Pierre Bassand et al. ESC Guidelines for the management of acute

coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).  European Heart Journal (2011) 32, 2999–3054

[4] Stephen J. Nicholls et al. Effect of Two Intensive Statin Regimens on Progression of Coronary Disease. N Engl J Med 2011;365:2078-87