Lene Kløvgaard

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.

BACKGROUND Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. METHODS We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. FINDINGS From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004). INTERPRETATION In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. FUNDING Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Randomized comparison of distal protection versus conventional treatment in primary percutaneous coronary intervention: the drug elution and distal protection in ST-elevation myocardial infarction (DEDICATION) trial.

OBJECTIVES The purpose of this study was to evaluate the use of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in native coronary vessels. BACKGROUND Embolization of material from the infarct-related lesion during PCI may result in impaired myocardial perfusion and worsen the prognosis. Previous attempts to protect the microcirculation during primary PCI have had conflicting results. METHODS We randomly assigned 626 patients with STEMI referred within 12 h to have PCI performed with (n = 312) or without (n = 314) distal protection. The primary end point was complete (>or=70%) ST-segment resolution detected by continuous ST-segment monitoring. Blood levels of troponin-T and creatine kinase-MB were monitored before and after the procedure, and echocardiographic determination of the left ventricular wall motion index (WMI) was performed before discharge. RESULTS Patients were well matched in terms of demographic and angiographic baseline characteristics. There was no significant difference in the occurrence of the primary end point (76% vs. 72%, p = 0.29), no difference in maximum troponin-T (4.8 microg/l and 5.0 microg/l, p = 0.87) or maximum creatine kinase-MB (185 microg/l and 184 microg/l, p = 0.99), and no difference in median WMI (1.70 vs. 1.70, p = 0.35). The rate of major adverse cardiac and cerebral events (MACCE) 1 month after PCI was 5.4% with distal protection and 3.2% with conventional treatment (p = 0.17). CONCLUSIONS The routine use of distal protection by a filterwire system during primary PCI does not seem to improve microvascular perfusion, limit infarct size, or reduce the occurrence of MACCE.

Long-Term Outcome After Drug-Eluting Versus Bare-Metal Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction: 5 Years Follow-Up From the Randomized DEDICATION Trial (Drug Elution and Distal Protection in Acute Myocardial Infarction)

OBJECTIVES This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. BACKGROUND The randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) trial evaluated the outcome after DES compared with BMS implantation in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS Patients with a high-grade stenosis/occlusion of a native coronary artery presenting with symptoms <12 h and ST-segment elevation were enrolled after giving informed consent. Patients were randomly assigned to receive a DES or a BMS in the infarct-related lesion. Patients were followed for at least 5 years, and clinical endpoints were evaluated from population registries and hospital charts. The main endpoint was the occurrence of the first major adverse cardiac event (MACE), defined as cardiac death, nonfatal recurrent myocardial infarction, and target lesion revascularization. RESULTS Complete clinical status was available in 623 patients (99.5%) at 5 years follow-up. The combined MACE rate was insignificantly lower in the DES group (16.9% vs. 23%), mainly driven by a lower need of repeat revascularization (p = 0.07). Whereas the number of deaths from all causes tended to be higher in the DES group (16.3% vs. 12.1%, p = 0.17), cardiac mortality was significantly higher (7.7% vs. 3.2%, p = 0.02). The 5-year stent thrombosis rates were generally low and similar between the DES and the BMS groups. No cardiac deaths occurring within 1 month could be clearly ascribed to stent thrombosis, whereas stent thrombosis was involved in 78% of later-occurring deaths. CONCLUSIONS The 5-year MACE rate was insignificantly different, but the cardiac mortality was higher after DES versus BMS implantation in patients with STEMI. Stent thrombosis was the main cause of late cardiac deaths.

Long-Term Outcome in Patients Treated With Sirolimus-Eluting Stents in Complex Coronary Artery Lesions: 3-Year Results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) Trial

OBJECTIVES Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions. BACKGROUND Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions. METHODS We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted. RESULTS At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient. CONCLUSIONS A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658)

Long-Term Outcome After Drug-Eluting Versus Bare-Metal Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction: 3-Year Follow-Up of the Randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) Trial

OBJECTIVES The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND The evidence of long-term efficacy and safety after implantation of DES in patients with complex lesions is scarce. METHODS We randomly assigned 626 patients with STEMI referred within 12 h to have a DES or a BMS implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. RESULTS At 3 years, target lesion revascularization was 6.1% in the DES group compared with 16.3% in the BMS group (p<0.001), and the rate of major adverse cardiac events was 11.5% versus 18.2%, respectively (p=0.02). Whereas all-cause mortality did not differ significantly, the rate of cardiac death was higher in the DES group, 6.1% versus 1.9% for the BMS group (p=0.01). The occurrence of reinfarction, stroke, and stent thrombosis was similar. CONCLUSIONS Implantation of DES in patients with STEMI reduces the long-term rate of major adverse cardiac events compared with BMS, but patients with DES had a higher risk of cardiac death not attributed to myocardial infarction or stent thrombosis. (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION]; NCT00192868)

Deferred stent implantation in patients with ST-segment elevation myocardial infarction: a pilot study

AIMS Disturbance in the flow of an infarct-related artery due to embolisation of thrombus and plaque material occurs frequently during primary percutaneous coronary intervention (PCI) and is associated with impaired prognosis. The aim of the present study was to minimise the risk of embolisation during PCI in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS Of 124 consecutive patients with STEMI, thrombectomy and/or balloon dilatation was performed in 110 (89%). Stent implantation was deferred in 113 (91%) patients who then comprised the study group. In 38% of the patients stent implantation was deemed unnecessary at the second examination because of <30% residual stenosis and no visible thrombus, and all lesions re-examined three months later were patent. Major adverse cardiac events occurred in two patients during eight months of follow-up (one cardiac death, one case of reinfarction with target lesion revascularisation). In five patients no PCI was performed at all. Myocardial salvage determined by cardiac magnetic resonance in a subset of patients was relatively high. CONCLUSIONS Deferred stent implantation is safe in the majority of patients with STEMI. Although the concept has to be evaluated in a randomised trial, the strategy may prove beneficial for many patients referred for primary PCI.

The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: Ischemic postconditioning or deferred stent implantation versus conventional primary angioplasty and complete revascularization versus treatment of culprit lesion only: Rationale and design of the DANAMI 3 trial program

BACKGROUND In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, ischemic postconditioning has been shown to reduce infarct size, but the effect on clinical outcome has not been tested in a large randomized trial. In addition, deferring stent implantation in the infarct-related lesion 1 to 3 days after acute opening of the infarct-related artery could have protective effects, by reducing the risk of injury caused by distal embolization and microvascular obstruction. Finally, a considerable fraction of patients present with lesions in other coronary artery branches than the infarct-related artery. Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain. STUDY DESIGN The DANAMI 3 trial program was designed to investigate 3 different randomized treatment strategies in patients with ST-segment elevation myocardial infarction: (1) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure; (2) deferring stent implantation in the infarct-related lesion versus conventional treatment with a primary end point of death, hospitalization for heart failure, reinfarction, and repeat revascularization; and (3) treatment of the culprit lesion only versus fractional flow reserve-guided complete revascularization in patients with multivessel disease, with a primary end point of death, reinfarction, and repeat revascularization. SUMMARY The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization.

Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial.

OBJECTIVES The purpose of this study was to evaluate the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND The use of distal filter protection during primary PCI increases procedure complexity and may influence lesion treatment and stent implantation. METHODS The STEMI patients were assigned to distal protection (DP) (n = 312) or conventional treatment (CT) (n = 314). Clinical follow-up was performed after 1, 6, and 15 months, and angiographic follow-up after 8 months. All target lesion revascularizations (TLRs) were clinically driven. We report the pre-specified end points of stent thrombosis according to the criteria of the Academic Research Consortium, TLR, and reinfarction after 15 months. RESULTS The total number of stent thrombosis was 11 in the DP group and 4 in the CT group (p = 0.06). The rate of definite stent thrombosis was significantly increased in the DP group as compared with the CT group, with 9 cases versus 1 (p = 0.01). Clinically driven TLRs (31 patients vs. 18 patients, p = 0.05) and clinically driven target vessel revascularizations (37 patients vs. 22 patients, p = 0.04) were more frequent in the DP group. CONCLUSIONS In primary PCI for STEMI, the routine use of DP increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization during 15 months of follow-up. (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction Trial [DEDICATION]; NCT00192868).

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial

Importance Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage. Objective To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, And Participants In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat. Interventions Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation. Main Outcome and Measures A combination of all-cause death and hospitalization for heart failure. Results During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure. Conclusions and Relevance Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival. Trial Registration clinicaltrials.gov Identifier: NCT01435408

Fractional Flow Reserve-Guided Complete Revascularization Improves the Prognosis in Patients With ST-Segment-Elevation Myocardial Infarction and Severe Nonculprit Disease: A DANAMI 3-PRIMULTI Substudy (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization).

Background— The impact of disease severity on the outcome after complete revascularization in patients with ST-segment–elevation myocardial infarction and multivessel disease is uncertain. The objective of this post hoc study was to evaluate the impact of number of diseased vessel, lesion location, and severity of the noninfarct-related stenosis on the effect of fractional flow reserve–guided complete revascularization. Methods and Results— In the DANAMI-3-PRIMULTI study (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), we randomized 627 ST-segment–elevation myocardial infarction patients to fractional flow reserve–guided complete revascularization or infarct-related percutaneous coronary intervention only. In patients with 3-vessel disease, fractional flow reserve–guided complete revascularization reduced the primary end point (all-cause mortality, reinfarction, and ischemia-driven revascularization; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.17–0.64; P=0.001), with no significant effect in patients with 2-vessel disease (HR, 0.77; 95% CI, 0.47–1.26; P=0.29; P for interaction =0.046). A similar effect was observed in patients with diameter stenosis ≥90% of noninfarct-related arteries (HR, 0.32; 95% CI, 0.18–0.62; P=0.001), but not in patients with less severe lesions (HR, 0.72; 95% CI, 0.44–1.19; P=0.21; P for interaction =0.06). The effect was most pronounced in patients with 3-vessel disease and noninfarct-related stenoses ≥90%, and in this subgroup, there was a nonsignificant reduction in the end point of mortality and reinfarction (HR, 0.32; 95% CI, 0.08–1.32; P=0.09). Proximal versus distal location did not influence the benefit from complete revascularization. Conclusions— The benefit from fractional flow reserve–guided complete revascularization in ST-segment–elevation myocardial infarction patients with multivessel disease was dependent on the presence of 3-vessel disease and noninfarct diameter stenosis ≥90% and was particularly pronounced in patients with both of these angiographic characteristics. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01960933.