ACCEL
Long-term or Short-term Dual Antiplatelet Therapy Following PCI?
March 01, 2017.Deepak Bhatt, MD, FACC, Boston, MA
Educational Objectives
Explain why studies have come to different conclusions regarding optimal length of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention, as well as identify patients who may be candidates for shorter-term or longer-term DAPT.
Summary
Interviewer: Carl J. Pepine, MD, MACC
Take-home Messages:
- There has been considerable debate (and shifting guideline recommendations) relating to the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) and implantation of drug-eluting stents (DES), largely because of the varying results of numerous clinical trials.
- Since the studies were individually underpowered to be definitive, meta-analysis has now been used to bring some clarity to this critical issue.
- The bottom line: it is important to individualize therapy based on risks for ischemia and bleeding. Given the large amount of available data, it is possible to offer recommendations that should assist the decision-making process regarding the optimal duration of DAPT.
DAPT is the cornerstone of therapy following PCI and DES implantation. Although treatment for 12 months is the standard of care in many parts of the world, the optimal duration of treatment is still controversial, largely because different studies have led to very different conclusions. Alon Eisen, MD, and Deepak Bhatt, MD, MPH, recently offered some clarity on the issue, noting meta-analysis results suggesting that shorter or longer durations might yield preferred outcomes in different patient subgroups.1
There had to be some explanation for the reported results from various studies supporting DAPT for 3 months, 6 months, and 12 months or longer. The big issue was that these studies were individually underpowered to be definitive, although collectively they were persuasive: in 2014, the European guidelines on myocardial revascularization changed the recommendation for DAPT duration from 1 year to 6 months based on results from second-generation DES studies.2
In contrast, the recently completed randomized DAPT trial reported that in 9,965 patients, prolonging DAPT from 1 year to 2.5 years after DES placement reduced the long-term risk of stent thrombosis, myocardial infarction (MI), and major adverse cardiovascular events (MACE) by preventing both stent-related and non-stent-related events.3
One big issue: prolonged DAPT substantially increased major bleeding, with a strong trend toward increased rates of all-cause mortality driven by greater noncardiovascular mortality due to bleeding, trauma, and cancer. Because death was not the primary endpoint of this study and the results were of borderline significance, it was unclear whether the increase in mortality was attributable to chance. If real, an increased risk of mortality of even ≈0.5% with extended DAPT (as seen in the DAPT trial) would represent tens of thousands of excess deaths in the millions of patients treated with DES every year worldwide.
The Bigger Picture
Thus, Palmerini et al. conducted a meta-analysis of 10 trials published between December 16, 2011, and November 16, 2014, including 31,666 randomly assigned patients.4 They reported that shorter DAPT duration was associated with significantly lower all-cause mortality compared with longer-duration DAPT (hazard ratio [HR]: 0.82; 95% confidence interval [CI] 0.69 to 0.98; p = 0·02); number needed to treat [NNT]: 325), with no significant heterogeneity across trials.
The reduced mortality with shorter compared with longer DAPT was attributable to lower noncardiac mortality (HR: 0.67; 95% CI: 0.51 to 0.89; p = 0.006; NNT: 347), with similar cardiac mortality (p = 0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of MI and stent thrombosis. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of MI and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for ≤6 months had similar rates of mortality, MI, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT.
The bottom line: Although treatment with DAPT beyond 1 year after DES implantation reduces MI and stent thrombosis, this meta-analysis indicates that extended DAPT is associated with increased mortality because of an increased risk of noncardiovascular mortality that is not offset by the reduction in cardiac mortality.
More recently, Dr. Bhatt and colleagues conducted a meta-analysis of long-term DAPT in 33,435 patients with previous MI.5 This is a group known to be at higher atherothrombotic risk compared to patients with stable ischemic heart disease treated with elective PCI. Over a mean of 31 months, compared with aspirin alone, extended DAPT beyond 1 year decreased the risk of MACE and cardiovascular mortality (Table). There was no increase in noncardiovascular death (p = 0.76) and no significant effect on all-cause mortality (p = 0.13).
Extended DAPT reduced MI (relative risk [RR]: 0.70; p = 0.003), stroke (RR: 0.81; p = 0.02), and stent thrombosis (RR: 0.50: p = 0.02). While extended DAPT increased the risk of major bleeding, it did not increase fatal bleeding, nor was there any excess of noncardiovascular causes of death (Table).
Dr. Bhatt and coauthors concluded: “These findings now clarify that in patients with prior MI who are at low risk of bleeding, continuation of DAPT beyond a year offers a substantial reduction in important cardiovascular outcomes and should be considered.”
So, what’s the optimal duration of DAPT? Here is what Dr. Bhatt, the executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, takes away from the evidence:1
- Twelve months or less of DAPT is appropriate in patients with stable coronary artery disease and a history of bleeding or at high risk of bleeding. Other factors include a short lesion, single-vessel disease, or the use of a second-generation DES.
- Consider extended (≥12 months) DAPT in patients with any history of acute coronary syndrome. It might also be appropriate in patients with diabetes mellitus, renal dysfunction, heart failure, previous stent thrombosis, or peripheral arterial disease. Anatomy-related factors include a long lesion, small vessel, bifurcation lesion, complex anatomy, or intervention involving the left-main coronary artery. Stent-related factors: first-generation DES, long stent, or multiple stents.
Meta-analysis Comparing Outcomes Associated with Extended DAPT vs. Aspirin Alone
|
| Extended DAPT | Aspirin Alone | Risk Ratio | p Value |
| MACE | 6.4% | 7.5% | 0.78 | 0.001 |
| Cardiovascular death | 2.3% | 2.6% | 0.85 | 0.03 |
| Major bleeding | 1.85% | 1.09% | 1.73 | 0.004 |
| Fatal bleeding | 0.14% | 0.17% | 0.91 | 0.75 |
CI = confidence interval; DAPT = dual antiplatelet therapy; MACE = major adverse cardiovascular events
Readings
1. Eisen A, Bhatt DL. Defining the optimal duration of DAPT after PCI with DES. Nat Rev Cardiol 2015;12:445-6.
2. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: Eur Heart J 2014;35:2541-619.
3. Mauri L, Kereiakes DJ, Yeh RW, et al, and the DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014;371:2155-66.
4. Palmerini T, Benedetto U, Bacchi-Reggiani L, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet 2015;385:2371-82.
5. Udell JA, Bonaca MP, Collet JP, et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J 2016;37:390-9.
Disclosures
Deepak Bhatt, MD, MPH, FACC
Elsevier BV (C); Duke Clinical RI (C);Takeda Pharmaceutical Co Ltd (C); The Medicines Company (G); Johnson and Johnson Services Inc (G); Medscape (G); Bristol-Myers Squibb Co (G); AstraZeneca (G); Sanofi (G); Eisai Co Ltd (G); Medtronic (G); PLx Pharma (G); Amarin Corp (G); FlowCo Inc (G); WebMD (O); Slack Publications/Cardiology Research Foundation (O)
Interviewer: Carl J. Pepine, MD, MACC
Eli Lilly and Co (D); Medtelligence LLC (C); Gilead (G); Pfizer Inc (G); Sanofi (G); Astellas Pharma Inc (G); Caladrius (G); Cytori Therapeutics Inc (G); Infraredx Inc (G); Baxter (G)
The planning committee reported nothing to disclose.
A = Advisory panel B = Speakers’ bureau C = Consultant fees/honoraria D = Data and Safety Monitoring Board E = Equity interests/stock options F = Fellowship support G = Grant support L = Licensing Agreement O = Other relationship R = Royalties S = Salary W = Expert witness
Acknowledgements
CME/CE INFO
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The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Lecture ID:
AC490320
Expiration:
This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.
Instructions:
To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.
Estimated time to complete this CME/CE course:
Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.
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