a systematic review of DAPT for the 2016 PCI guideline update . 4 The evidence is based on an analysis of 11 RCTs enrolling a total of 33,051 patients ( mostly receiving newer-generation DES ).
Six RCTs compared 18 to 48 months with 6 to 12 months of DAPT and the analysis of data found reductions in MI and stent thrombosis , no difference in major adverse cardiac events ( MACE ), an increase in major hemorrhage , and no change in mortality in the primary analyses . That might seem to be a positive finding , compared with the previously mentioned meta-analysis ; however , secondary analyses of trials stratified by enrollment demonstrated “ weak evidence ” of increased mortality with prolonged DAPT in RCTs that successfully achieved their predefined enrollment targets .
As to the question about using extending therapy in patients more than 1 to 3 years after MI , this new meta-analysis , conducted for the guidelines , showed a significant reduction in MACE but an increase in major hemorrhage . Moreover , the evidence suggests that the net benefit of extending DAPT is not static but dynamic as a function of the bleeding and thrombotic propensity for each patient being treated .
Overall , the new analysis of RCTs suggests that patients undergoing safer , newer-generation DES implantation may be treated with a minimum DAPT duration of 3 to 6 months to prevent early and largely stent-related thrombotic events , but extension of DAPT beyond 12 months entails a tradeoff . The declining risk of late stent thrombosis with newer-generation DES and the inability to predict life-threatening bleeding limits the appeal of 18 to 48 months of DAPT over 6 to 12 months of therapy . In contrast , patients with prior MI at high risk of atherothrombosis experience fewer ischemic events with prolonged DAPT at a cost of increased bleeding events .
The systematic review has now been published , 4 as has a new ACC / AHA PCI guidelines update . 5 To see a review of the overriding concepts and updated recommendations for DAPT use and duration , please see the TABLE below .
REFERENCES :
1 . Levine GN , Bates ER , Blankenship JC , et al . 2011 J Am Coll Cardiol . 2011 ; 58 : e44-122 .
2 . Kereiakes DJ , Yeh RW , Massaro JM , et al . Lancet . 2015 ; 385:2371-82 .
3 . Bittl JA , Baber U , Bradley SM , Wijeysundera DN . J Am Coll Cardiol . 2016 [ Epub ahead of print ].
4 . Levine GN , Bates ER , Bittl JA , et al . J Am Coll Cardiol . 2016 [ Epub ahead of print ]. http :// content . onlinejacc . org / article . aspx ? doi = 10.1016 / j . jacc . 2016.03.513
Take-aways
• The extent of benefit and risk with various periods of DAPT after DES placement has been evaluated in multiple observational studies and RCTs .
• The ACC / AHA recently conducted a systematic review and meta-analysis , which has led to the publication of an ACC / AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients with Coronary Artery Disease .
TABLE Overriding Concepts and Updated Recommendations for DAPT and Duration
Intensification of antiplatelet therapy , with the addition of a P2Y12 inhibitor to aspirin monotherapy , as well as prolongation of DAPT , necessitates a fundamental tradeoff between decreasing ischemic risk and increasing bleeding risk . Decisions about treatment with and duration of DAPT require a thoughtful assessment of the benefit / risk ratio , integration of study data , and consideration of patient preference .
In general , shorter-duration DAPT can be considered for patients at lower ischemic risk with high bleeding risk , whereas longer-duration DAPT may be reasonable for patients at higher ischemic risk with lower bleeding risk .
Prior recommendations for duration of DAPT for patients treated with DES were based on data from “ first-generation ” DES , which are rarely , if ever , used in current clinical practice . Compared with first-generation stents , newer-generation stents have an improved safety profile and lower risk of stent thrombosis . Recommendations in this focused update apply to newer-generation stents .
Updated recommendations for duration of DAPT are now similar for patients with NSTE-ACS and STEMI , as both are part of the spectrum of acute coronary syndrome .
A Class I recommendation (“ should be given ”) in most clinical settings is made for at least 6-12 months of DAPT ( depending on the setting ), and a Class IIb recommendation (“ may be reasonable ”) is made for prolonged DAPT beyond this initial 6- to 12-month period .
In studies of prolonged DAPT after DES implantation or after MI , duration of therapy was limited to several years ( akin to many other studied therapies ). Thus , in patients for whom the benefit / risk ratio seemingly favors prolonged therapy , the true optimal duration of therapy is unknown .
Recommendations in the document apply specifically to duration of P2Y12 inhibitor therapy in patients with coronary artery disease treated with DAPT . Aspirin therapy should almost always be continued indefinitely in patients with CAD .
Lower daily doses of aspirin , including in patients treated with DAPT , are associated with lower bleeding complications and comparable ischemic protection than are higher doses of aspirin . The recommended daily dose of aspirin in patients treated with DAPT is 81 mg ( range : 75 mg to 100 mg ).
Prevalence of Resistant Hypertension is Increasing ( or Not )
High levels of blood pressure ( BP ) are associated with premature death , stroke , cardiovascular events , and renal failure . Antihypertensive therapy reduces this risk , but some patients seem resistant to therapy .
According to 2005 to 2008 National Health and Nutrition Examination Survey data , 11.8 % of U . S . adults with hypertension met the criteria for resistant hypertension : systolic / diastolic BP ≥ 140 / 90 mm Hg despite the use of antihypertensive medications from three different drug classes or drugs from four or more antihypertensive drug classes regardless of BP . 1 This represents a doubling in prevalence from 5.5 % in 1998 to 1994 and a nearly 40 % increase from that reported in 1999 to 2004 ( 8.5 %).
Michael A . Weber , MD , professor of medicine , State University of New York , Downstate Medical Center , recently offered advice to clinicians facing a patient with apparent resistant hypertension . 2 In brief :
According to 2005 to 2008 National Health and Nutrition Examination Survey data , 11.8 % of U . S . adults with hypertension met the criteria for resistant hypertension .
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