Keywords
acute myocardial infarction - antiplatelet therapy - adherence to treatment
Introduction
Antiplatelet therapy represents the cornerstone therapy in patients with acute coronary
syndrome (ACS). Prolonged dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is recommended up to 1 year after ACS both in patients submitted to revascularization
and in patients medically managed.[1]
[2]
[3]
Notably, only in the late years a mounting evidence for secondary prevention by intensified
antiplatelet therapy has emerged after 1 year from ACS. It has been recently demonstrated
that, in patients presenting with ACS, the ischemic risk can remain substantially
elevated beyond the first 12 months, in spite of a successful revascularization. The
DAPT[4] and the PEGASUS-TIMI 54[5] trials demonstrated that prolonged DAPT beyond 12 months can significantly reduce
the incidence of major adverse cardiac events (MACE). In this setting, intensified
antiplatelet therapy on top of aspirin has been shown to be an effective therapeutic
strategy to prevent recurrent ischemic events. In selected patients at high thrombotic
risk, prolonged DAPT beyond 12 months might be considered.[1]
[2]
[3]
The need for prolonged DAPT might raise compliance issues, as long-term adherence
to prescribed therapy after ACS is still challenging in real-world patients.[6]
Previous reports have shown that more than 10% of patients prematurely discontinue
antiplatelet therapy within 30 days after stent implantation. Clinical trials reported
a rate of premature discontinuation as high as 30% after 12 months.[7] Premature antiplatelet therapy discontinuation raises safety concerns, as it is
associated with a higher incidence of MACE.[6]
[8] Nonadherent patients are at a substantially higher risk of death.[9] Patients with ACS who discontinue all of their medications are more than three times
as likely to die as those who remain adherent. Of note, the rate and clinical consequences
of antiplatelet discontinuation beyond 12 months after ACS in real-world patients
are still lacking.
The aim of our study is to assess long-term exposure and adherence to DAPT in patients
with ACS in an Italian population. The occurrence of MACE in relation to maintenance
of single- or dual-antiplatelet therapy has been investigated, as well.
Methods
Data Sources
The PIPER (Platelet-aggregation Inhibition: Persistence with treatment and cardiovascular
Events in Real-world Study) is a retrospective, observational study, based on administrative
databases of eight Italian Local Health Units (LHUs), in Lombardy, Tuscany, Puglia,
and Campania, which includes approximately 5.6 million health-assisted individuals.
In particular, the following databases were used as data sources: the Health-Assisted
Subjects' Database, containing patients' demographic data; Outpatients and Inpatients
pharmaceutical drugs, providing information for each medication prescription, such
as ATC (Anatomical-Therapeutic-Chemical) code of the drug purchased, number of packages,
number of units per package, the dosages, unit cost per package, and prescription
date; and Hospital Discharge Database, which includes all hospitalization data with
discharge diagnosis codes classified according to the International Classification
of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The patient code in
each database permitted electronic linkage with all the other databases. No identifiers
related to patients were provided to the researchers. Informed consent was not required
for using encrypted retrospective information. This study was notified to the local
ethics committee in each participating LHU according to the Italian law regarding
the conduct of observational analysis, and the LHU Ethics Committees approved the
study.[10]
Study Populations
This was a retrospective cohort study that included all consecutive beneficiaries
of each LHUs hospitalized and discharged alive with a primary diagnosis of acute myocardial
infarction (AMI; ICD-9-CM: 410.xx) between January 1, 2010, and December 31, 2011
(enrollment period). The date of AMI discharge was identified as the index date, which
represented the enrollment day of each individual patient, who was then followed up
for 3 years after the index date (follow-up period).
Data on baseline characteristics, including demographics, risk factors, and medical
history, were collected. Specifically, the treatments of interest were antihypertensive
drugs (ATC codes: C02, C03, C08), oral hypoglycemic drugs and/or insulins (ATC code:
A10), cardiac therapy (ATC code: C01), statins (ATC code: C10AA), beta-blocking agents
(ATC code: C07), angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor
antagonists (AAIIs; ATC code: C09). Previous cardiovascular hospitalizations were
identified by ICD-9-CM codes: 410–414; history of percutaneous coronary intervention
(PCI) (procedure codes: 00.66, 36.0x or absence of 36.04) and AMI of other than anterior
wall (ICD-9-CM codes: 410.0 or 410.1) were also evaluated.
Patients were classified according to exposure to antiplatelet therapy during the
follow-up period. A patient was defined as treated with antiplatelet therapy (ATC
code: B01AC), if at least two prescriptions of these drugs during the follow-up period
were found. In particular, all enrolled patients were stratified into four main categories:
(1) monotherapy with acetylsalicylic acid (ASA); (2) DAPT (ASA + P2Y12 inhibitors); (3) other drugs (only P2Y12 inhibitors); and (iv) no antiplatelet therapy.
Patients with concomitant diagnosis at discharge of anemia or cancer were excluded,
as these comorbidities might influence prescription and/or duration of DAPT.
Hospitalizations for AMI and all-cause mortality occurring during the 36-month follow-up
period from discharge were considered. Multivariable analyses were conducted to check
for possible confounders using a proportional hazards Cox regression model: demographic
characteristics; other guidelines-recommended post-AMI therapies, including beta-blockers,
ACE inhibitors/AAIIs, statin, and antiplatelet therapy; previous hospitalizations
for cardiovascular disorders; and diabetes.
A patient was defined as antidiabetic, antihypertensive, or cardiac therapy if at
least two prescriptions of antidiabetic agents, of antihypertensives, of cardiac drugs,
respectively, were found at follow-up. A patient was defined as treated with statins,
beta-blocking agents, or ACE inhibitors/AAIIs if at least two prescriptions of these
drugs were detected during the observation period. Patients who were transferred to
another LHU during the observational period were excluded from analysis.
A Pegasus score was calculated for each patient by the sum of the characteristics
which constituted the inclusion criteria of the Pegasus trial.[5]
Statistical Methods
Continuous variables are given as means with standard deviations (mean ± SD); categorical
variables are shown as percentages and absolute numbers.
Cox regression analysis has been used for the risk assessment. The impact of different
variables on cardiovascular mortality and recurrent AMI was analyzed using the hazard
ratios (HR) with 95% confidence interval (CI); a p-value less than 0.05 was considered statistically significant. Analyses were performed
with Stata software version 12.1 (Stata Corp LP, College Station, Texas, United States).
Results
A total of 11,101 were discharged alive with a primary diagnosis of AMI. Of these,
5,919 patients (53.3%) were discharged on DAPT, without a diagnosis of cancer or anemia
at discharge, without transient DAPT discontinuation, and represented our study population
([Fig. 1]).
Fig. 1 Flow chart for patient selection and inclusion and exclusion criteria for study.
DAPT, dual-antiplatelet therapy; AMI, acute myocardial infarction; ASA, acetylsalicylic
acid. Notes: §DAPT = ASA + P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor, ticlopidine); *At least one prescription
of ASA and at least one prescription of P2Y12 in the month following hospital discharge; **Any prescription of ASA or P2Y12 in the 3 months following hospital discharge.
The demographic and baseline clinical characteristics of included patients are shown
in [Table 1]. Among the enrolled patients, 55.6% presented hypertension at the baseline, followed
by 43.9% with heart disease, 26.0% with diabetes, and 10.0% with previous hospitalization
for cardiovascular disorders. Statins, ACE inhibitors/AAIIs, and beta-blocking agents
were used in 79.4, 74.6, and 71.5%, respectively. PCI at the index hospitalization
was performed in 52.9% of patients. [Table 2] describes the type of DAPT.
Table 1
Demographic and clinical characteristics of included patients
N, %
|
11,101
|
100.0%
|
Age (y)
|
65.6 ± 17.6
|
Male
|
7,000
|
63.1%
|
Previous cardiovascular hospitalizations
|
1,114
|
10.0%
|
Diabetes
|
2,885
|
26.0%
|
Hypertension
|
6,167
|
55.6%
|
Heart disease
|
4,878
|
43.9%
|
ACE inhibitors/AAIIs
|
8,285
|
74.6%
|
Statins
|
8,819
|
79.4%
|
Beta-blocking agents
|
7,942
|
71.5%
|
Index MI: front/front-lateral
|
2,889
|
26.0%
|
Index MI with PCI
|
5,872
|
52.9%
|
Index MI with coronary angiography
|
5,821
|
52.4%
|
CKD
|
232
|
2.1%
|
Abbreviations: AAII, angiotensin II receptor antagonist; ACE, angiotensin-converting
enzyme; CKD, chronic kidney disease; MI, myocardial infarction; PCI, percutaneous
coronary intervention.
Table 2
Type of antiplatelet treatment
Type of treatment
|
|
|
N
|
%
|
%
|
None
|
|
|
1,882
|
17.0
|
–
|
Treatment
|
|
|
9,219
|
83.0
|
100.0
|
|
Monotherapy
|
ASA
|
1,659
|
14.9
|
18.0
|
|
|
P2Y12
|
854
|
7.7
|
9.3
|
|
DAPT
|
ASA + Clopidogrel
|
6,313
|
56.9
|
68.4
|
ASA + Prasugrel
|
266
|
2.4
|
2.9
|
ASA + Ticagrelor
|
10
|
0.1
|
0.1
|
ASA + Ticlopidine
|
117
|
1.1
|
1.3
|
Total
|
|
|
|
100.0
|
–
|
Abbreviations: ASA, acetylsalicylic acid; DAPT, dual-antiplatelet therapy (ASA + P2Y12).
Out of the 5,919 patients, 2,200 (37.2%) discontinued DAPT after the first semester
and 1,995 (33.7%) discontinued DAPT after the second semester ([Supplementary Fig. S1]). Of note, 423 patients (7.1%) were still on DAPT after 36 months.
Baseline clinical and demographic characteristics of patients in relation to exposure
and type of antiplatelet therapy are summarized in [Table 3]. Compared with patients who were still on DAPT at 6 months, patients who were on
DAPT at 12 months were younger (mean age: 62.5 ± 16.0 vs. 65.5 ± 17.0, p < 0.001), less frequently required blood transfusion (3.9 vs. 6.9%, p < 0.001), and had less frequently chronic kidney disease (1.1 vs. 2.2%, p < 0.01). Patients who were still on DAPT at 3 years had more frequently a previous
cardiovascular hospitalization (8.8 vs. 14.4%, p < 0.001) and were more frequently diabetic (38.5 vs. 25.5%, p < 0.001), compared with patients who discontinued after 12 months.
Table 3
Demographic and clinical characteristics of patients by semester of DAPT interruption
|
Patients who discontinued DAPT after semester 1
|
Patients who discontinued DAPT after semester 2
|
Patients who discontinued DAPT after semester 3
|
Patients who discontinued DAPT after semester 4
|
Patients who discontinued DAPT after semester 5
|
Patients still in DAPT at semester 6
|
p-Value
|
N, %
|
2,200
|
1,995
|
807
|
324
|
170
|
423
|
|
37.2%
|
33.7%
|
13.6%
|
5.5%
|
2.9%
|
7.1%
|
|
Age (y)
|
65.5 ± 17.0
|
62.5 ± 16.0
|
61.4 ± 15.9
|
62.0 ± 17.6
|
61.8 ± 16.9
|
61.7 ± 17.9
|
0.001
|
Male
|
1,434
|
1,424
|
558
|
211
|
119
|
275
|
|
65.2%
|
71.4%
|
69.1%
|
65.1%
|
70.0%
|
65.0%
|
0.01
|
Previous cardiovascular hospitalizations
|
193
|
161
|
62
|
33
|
22
|
61
|
0.001
|
8.8%
|
8.1%
|
7.7%
|
10.2%
|
12.9%
|
14.4%
|
|
Diabetes
|
560
|
532
|
250
|
92
|
62
|
163
|
0.001
|
25.5%
|
26.7%
|
31.0%
|
28.4%
|
36.5%
|
38.5%
|
|
Hypertension
|
1,322
|
984
|
478
|
219
|
112
|
291
|
0.001
|
60.1%
|
49.3%
|
59.2%
|
67.6%
|
65.9%
|
68.8%
|
|
Heart disease
|
1,045
|
774
|
372
|
189
|
103
|
251
|
0.001
|
47.5%
|
38.8%
|
46.1%
|
58.3%
|
60.6%
|
59.3%
|
|
ACE inhibitors/AAIIs
|
1,806
|
1,718
|
726
|
283
|
156
|
382
|
0.001
|
82.1%
|
86.1%
|
90.0%
|
87.3%
|
91.8%
|
90.3%
|
|
Statins
|
1,946
|
1,938
|
793
|
320
|
164
|
413
|
0.001
|
88.5%
|
97.1%
|
98.3%
|
98.8%
|
96.5%
|
97.6%
|
|
Beta-blocking agents
|
1,736
|
1,710
|
693
|
282
|
154
|
365
|
0.001
|
78.9%
|
85.7%
|
85.9%
|
87.0%
|
90.6%
|
86.3%
|
|
Index MI: front/front-lateral
|
583
|
541
|
206
|
82
|
61
|
122
|
NS
|
26.5%
|
27.1%
|
25.5%
|
25.3%
|
35.9%
|
28.8%
|
|
Index MI with PCI
|
1,368
|
1,425
|
534
|
195
|
107
|
266
|
0.001
|
62.2%
|
71.4%
|
66.2%
|
60.2%
|
62.9%
|
62.9%
|
|
Index MI with coronary angiography
|
1,260
|
1,294
|
468
|
175
|
89
|
234
|
0.001
|
57.3%
|
64.9%
|
58.0%
|
54.0%
|
52.4%
|
55.3%
|
|
CKD
|
48
|
21
|
9
|
5
|
10
|
8
|
0.001
|
2.2%
|
1.1%
|
1.1%
|
1.5%
|
5.9%
|
1.9%
|
|
0.3%
|
0.4%
|
–
|
–
|
0.0%
|
1.4%
|
|
Abbreviations: AAII, angiotensin II receptor antagonist; ACE, angiotensin-converting
enzyme; CKD, chronic kidney disease; DAPT, dual-antiplatelet therapy; MI, myocardial
infarction; NI, not issuable; PCI, percutaneous coronary intervention.
After controlling for possible confounders, patients who maintained DAPT up to 12
months had with a significantly lower all-cause mortality, compared with patients
who discontinued DAPT after 6 months (HR: 0.531, 95% CI: 0.434–0.650, p < 0.001). Moreover, exposure to DAPT at 3 years (compared with no exposure to DAPT—no
treated patients or patients in monotherapy with ASA/P2Y12) was associated with reduced
all-cause mortality (HR: 0.067, 95% CI: 0.027–0.162, p < 0.001; [Fig. 2]) and recurrent AMI (HR: 0.02, 95% CI: 0.003–0.173, p < 0.001). PCI at the index hospitalization for AMI was found to be associated with
reduced all-cause mortality (HR: 0.678, 95% CI: 0.557–0.825, p < 0.001), but was not associated with reduced AMI ([Table 4]).
Table 4
All-cause mortality at 3 years in relation to DAPT maintenance
|
HR
|
95% confidential interval
|
p-Value
|
Age (y)
|
1.076
|
1.064
|
1.087
|
<0.001
|
Gender (ref. F)
|
1.576
|
1.316
|
1.886
|
<0.001
|
Previous cardiovascular hospitalizations (ref. no)
|
1.257
|
0.965
|
1.636
|
0.090
|
Diabetes (ref. no)
|
0.972
|
0.689
|
1.371
|
N.S.
|
Hypertension (ref. no)
|
0.820
|
0.579
|
1.160
|
N.S.
|
Heart disease (ref. no)
|
0.735
|
0.534
|
1.013
|
N.S.
|
ACE inhibitors/AAIIs (ref. no)
|
0.235
|
0.168
|
0.328
|
<0.001
|
Statins (ref. no)
|
0.574
|
0.458
|
0.720
|
<0.001
|
Beta-blocking agents (ref. no)
|
0.417
|
0.301
|
0.578
|
<0.001
|
Index MI: front/front-lateral (ref. no)
|
1.058
|
0.872
|
1.282
|
N.S.
|
Index MI with PCI (ref. no)
|
0.678
|
0.557
|
0.825
|
<0.001
|
Index MI with coronary angiography (ref. no)
|
0.950
|
0.783
|
1.153
|
N.S.
|
Neoplasia hosp. during obs. period (ref. no)
|
2.992
|
2.421
|
3.697
|
<0.001
|
Blood transfusion during obs. period (ref. no)
|
1.376
|
0.949
|
1.997
|
N.S.
|
DAPT maintenance
|
Patients who discontinued DAPT after semester 1
|
1.000
|
|
|
|
Patients who discontinued DAPT after semester 2
|
0.531
|
0.434
|
0.650
|
<0.001
|
Patients who discontinued DAPT after semester 3
|
0.455
|
0.330
|
0.628
|
<0.001
|
Patients who discontinued DAPT after semester 4
|
0.484
|
0.323
|
0.725
|
0.001
|
Patients who discontinued DAPT after semester 5
|
0.195
|
0.096
|
0.395
|
<0.001
|
Patients still in DAPT at semester 6
|
0.067
|
0.027
|
0.162
|
<0.001
|
Abbreviations: AAII, angiotensin II receptor antagonist; ACE, angiotensin-converting
enzyme; DAPT, dual-antiplatelet therapy; HR, hazard ratio; MI, myocardial infarction;
N.S., not significant; PCI, percutaneous coronary intervention.
Notes: N = 5,027, no. of events = 580.
Fig. 2 Mortality at 36 months of follow-up (Kaplan–Meier). NO DAPT: N = 3,540, no. of events = 749
(21.2%); survivals after 3 years = 2,791 (78.8%); DAPT: N = 5,027, no. of events = 580
(11.6%); survivals after 3 years = 4,447 (88.4%). LHUs of Frosinone and Grosseto were
excluded because data on deaths were not available.
Discussion
The main findings of this study are the following: adherence to DAPT within the first
12 months after AMI is still suboptimal; notably, a significant proportion of patients
in Italy maintain DAPT up to 36 months after AMI; cessation of DAPT within the first
12 months is associated with increased overall mortality; prolonged DAPT beyond 12
months seems to be associated with a significant reduction in all-cause mortality
and AMI.
The benefit of DAPT after an ACS was well demonstrated in the CURE,[11] COMMIT/CCS-28,[12] and CLARITY-TIMI 28[13] trials. The association of aspirin and clopidogrel reduced the 1-year incidence
of cardiovascular events by approximately 20% compared with aspirin alone. More potent
and consistent P2Y12 receptor inhibition with either prasugrel or ticagrelor was superior to clopidogrel
in the subsequent TRITON-TIMI 38[14] and PLATO[15] trials. Current guidelines recommend 12 months of DAPT after ACS.[1]
[2]
[3] These recommendations are made on the basis of early studies[16]
[17] which demonstrated a sustained increased risk of thrombotic complications, including
stent thrombosis and spontaneous cardiovascular events, beyond 6 months. Notably,
the greatest absolute reductions in cardiovascular events with DAPT are seen in the
first 3 months and since these studies, advances in drug-eluting stent technology
have led to a substantially reduced incidence of late (>30 days) and very late (>1
year) stent thrombosis.[10]
[18]
Although it has been fully elucidated that premature discontinuation of antiplatelet
therapy is associated with a poor prognosis, patients' compliance remains low.[6]
[7] Several reasons for noncompliance have been reported, such as excessive concerns
about hemorrhagic complications or competing guidelines, complex treatment regimens,
or lack of outcome expectancy.[19] As anemia can be considered a marker for high bleeding risk, thus contraindicating
prolonged DAPT, patients with anemia at discharge were excluded from the present analysis.
Nevertheless, in this study, one out of three patients discontinued DAPT after 6 months.
In routine clinical practice, poor medication adherence is one of the main factors
that reduce the effectiveness of chronic drug therapies.[20] In accordance with data observed in other studies,[6]
[21]
[22] in this study a considerable proportion of patients report low adherence to prescribed
medications, particularly for non-monotherapy strategies.
Although many studies have evaluated the incidence or effect of antiplatelet therapy
cessation on subsequent cardiovascular risk, most included selected cohorts of patients
and were limited by lack of standardized definitions for therapy discontinuation that
did not integrate the underlying context in which treatment was discontinued.[23]
[24] The results presented here suggest that there are still numerous barriers to adherence
to practice guidelines; therefore, encouragement to continue long-term therapy with
lifestyle modifications and pharmacological treatments is needed to improve outcomes
in patients at risk of cardiovascular events.[25]
On the other hand, this study demonstrated that the number of patients who maintain
DAPT up to 3 years after AMI is not trivial. It should be highlighted that the enrollment
period was from January 2010 to December 2011, previous to the recent publication
of data on prolonged DAPT beyond 12 months. This finding might be considered in the
light of the attempt of clinicians to provide a further protection for ischemic events
in patients considered high thrombotic risk, even without evidence of clear benefit.
The DAPT trial was designed on the basis of this unmet need. In the DAPT trial,[4] the largest and only double-blinded study, extended DAPT (30 vs. 12 months) reduced
the risk of major adverse cardiovascular and cerebrovascular events (4.3 vs. 5.9%),
myocardial infarction (MI; 2.1 vs. 4.1%), and stent thrombosis (0.4 vs. 1.4%) but
at a cost of increased moderate or severe bleeding (2.5 vs. 1.6%) and a borderline
rise in all-cause mortality (2.0 vs. 1.0%; p = 0.05). The PEGASUS-TIMI 54 trial[5] compared aspirin monotherapy to a combination of aspirin and ticagrelor in patients
with a previous MI and at least one additional high-risk factor. At a mean of 33 months,
ticagrelor (60 mg) reduced the incidence of cardiovascular death, MI, or stroke (7.77
vs. 9.04%) at the expense of increased thrombolysis in myocardial infarction (TIMI)
major bleeding (2.30 vs. 1.06%) and a neutral effect on overall mortality. On the
basis of these trials, combination antiplatelet therapy would appear to confer only
a small ischemic benefit at the cost of a significant bleeding risk. European[26] and North American[27] guidelines therefore do not recommend DAPT in patients with stable atherothrombotic
disease but acknowledge that with careful consideration, combined antiplatelet therapy
may be beneficial in some high-risk patients.
In this study, prolonged DAPT up to 3 years after AMI was associated with a significant
reduction in overall mortality and AMI. Due to the retrospective nature of the study,
this conclusion should be interpreted with caution and only as hypothesis generating.
It should be highlighted that prolonged DAPT might identify patient at lower hemorrhagic
risk, without noncardiac comorbidities which would have contraindicated long-term
DAPT. To reduce a selection bias, patients with anemia of cancer at discharge were
excluded, as well as patients who were not prescribed DAPT at discharge. An unexpected
finding in the DAPT trial[4] was a borderline-significant increase in overall mortality rate (0.5% absolute increase)
with 30 months of DAPT versus 12 months of DAPT in DES-treated patients, which was
due to significantly increased deaths from non-cardiovascular causes (most commonly
cancer), with no increase in cardiovascular deaths, and no significant increase in
fatal bleeding.
It should be highlighted that the prescription of DAPT at discharge was relatively
low. This might be partly explained by the enrollment period, which was from January
2010 to December 2011, when P2Y12 inhibitors in medically managed patients were still underused. Moreover, the analysis
included not only type I but also type II MI patients, for whom the benefit of DAPT
may be controversial. The low use of beta-blockers and ACE inhibitors was evident,
as well. The low use of ACE inhibitors might be due in some cases to preserved ejection
fraction.
The results of this study should be interpreted in light of some strengths and limitations.
The strength of the presented data includes its basis on the large size unselected
population; our patients may represent a more representative sample of “real world”
than those included in many of the randomized controlled trials that have previously
evaluated antiplatelet use for mortality reduction. Limitations include, first, the
absence of relevant clinical information in the data setting. It is plausible that
patients' risk profile might have conditioned DAPT duration. However, due to the nature
of the study, which consists of a retrospective analysis from administrative databases,
important clinical data are missing and confounding biases might have influenced the
results. To overcome this limitation, we excluded patients with concomitant diagnosis
at discharge of anemia or cancer, as these comorbidities might influence prescription
and/or duration of DAPT. It cannot be ruled out if the reduced all-cause mortality
associated with prolonged exposure to DAPT is related to a lower risk profile of patients
(in terms of comorbidities), which allowed prolonged DAPT, or the protective effect
of DAPT. Notably, prolonged DAPT was associated with a reduced rate of recurrent AMI,
for which the protective effect of DAPT might be more evident. Second, adherence was
estimated using pharmacy data on filled prescriptions, but no information on actual
medication consumption was available. Third, the reasons for nonadherence were not
retrievable from the dataset.
Despite these limitations, this study indicates prolonged DAPT beyond 12 months is
maintained in a relevant number of patients after AMI. Notably, long-term exposure
and adherence with antiplatelet therapy in patients with AMI still appear to be unsatisfactory
in an unselected Italian population. Further efforts to enhance patients' compliance
to medical therapy are warranted.