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Research · Medication

Antiplatelets: clopidogrel and low-dose aspirin

Meta-analyses found antiplatelet drugs cut serious vascular events by about a quarter in people with prior heart attack or stroke. For people without cardiovascular disease, aspirin prevented about 1 event per 265 people and caused 1 major bleed per 210. Clopidogrel carries an FDA boxed warning on reduced effect in CYP2C19 poor metabolizers.

Add to Bio HackChecked 2026-11-13
Status
Clopidogrel is a prescription drug in the US, FDA-approved with aspirin for acute coronary syndromes and alone after a recent heart attack, recent stroke or with established peripheral artery disease. Its label carries an FDA boxed warning on reduced effect in CYP2C19 poor metabolizers. Aspirin is sold over the counter and as a prescription extended-release capsule, which is approved to reduce death and heart attack in chronic coronary artery disease and death and repeat stroke after an ischemic stroke or transient ischemic attack.
Also called
clopidogrel, Plavix, aspirin, low-dose aspirin, baby aspirin, acetylsalicylic acid, ASA, Bayer Low Dose, Ecotrin, Durlaza, dual antiplatelet therapy, DAPT, P2Y12 inhibitor, blood thinners
Taken for
preventing a second heart attack, preventing a second stroke, after a stent, heart attack prevention, stroke prevention, daily aspirin for heart health, peripheral artery disease, preeclampsia prevention, colorectal cancer prevention

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help8

Reported risks19

What people take it for, and what was found

Shown to help8

StrongCommon

After a heart attack, stroke or with artery disease

Shown to cut serious vascular events by about a quarter in high-risk patients, about 36 fewer per 1,000 treated for two years after a heart attack.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Among high-risk patients, antiplatelet therapy lowered serious vascular events by about one quarter, nonfatal heart attack by one third, nonfatal stroke by one quarter and vascular death by one sixth. The absolute reduction was 36 per 1,000 treated for two years after a heart attack, 36 per 1,000 after a stroke or transient ischemic attack, and 38 per 1,000 treated for one month during an acute heart attack. Aspirin was the most widely studied drug [1]. In secondary prevention trials with individual data, serious vascular events occurred at 6.7% a year on aspirin against 8.2% on control, total stroke at 2.08% against 2.54% and coronary events at 4.3% against 5.3% [2].
Population
High-risk patients in a collaborative meta-analysis of randomized antiplatelet trials [1]; secondary prevention trials with individual participant data [2].
Sources
[1], [2]
Caveats
Both analyses come from the same collaboration. The band above is the absolute reduction of 36 per 1,000 over two years [1].
Moderate

Clopidogrel compared with aspirin

Shown to lower stroke, heart attack or vascular death slightly more than aspirin, 5.32% against 5.83% a year, in people with artery disease.

The numbers and sources
Effect
In people with a recent stroke, recent heart attack or peripheral artery disease, the yearly risk of ischemic stroke, heart attack or vascular death was 5.32% on clopidogrel against 5.83% on aspirin, a relative reduction of 8.7% (95% CI 0.3 to 16.5) [3]. A collaborative meta-analysis put the reduction in serious vascular events with clopidogrel against aspirin at 10% [1].
Population
19,185 patients followed a mean 1.91 years [3].
Sources
[3], [1]
Caveats
One large trial, with a confidence interval that nearly reached no difference [3].
Moderate

Clopidogrel added to aspirin during a heart attack or unstable angina

Shown to cut cardiovascular death, heart attack or stroke to 9.3% against 11.4% on aspirin alone in acute coronary syndromes, with more major bleeding.

The numbers and sources
Effect
In acute coronary syndromes without ST-segment elevation, cardiovascular death, nonfatal heart attack or stroke occurred in 9.3% on clopidogrel plus aspirin against 11.4% on aspirin alone (RR 0.80, 95% CI 0.72 to 0.90). Major bleeding occurred in 3.7% against 2.7% (RR 1.38) [4]. In acute heart attack, death, reinfarction or stroke occurred in 9.2% against 10.1% over about two weeks, a 9% reduction (95% CI 3 to 14), and death from any cause in 7.5% against 8.1% [5].
Population
12,562 patients treated for 3 to 12 months [4]; 45,852 patients with acute myocardial infarction [5].
Sources
[4], [5]
Caveats
In the second trial, fatal, transfused or cerebral bleeds did not differ (0.58% against 0.55%) over a short treatment period [5].
Moderate

After a coronary stent

Shown to cut stent clots to 0.4% against 1.4% and heart attacks to 2.1% against 4.1% when a thienopyridine was continued with aspirin beyond a year, with more bleeding.

The numbers and sources
Effect
After 12 months of aspirin plus clopidogrel or prasugrel following a drug-eluting stent, continuing the second drug for 18 more months lowered stent thrombosis (0.4% against 1.4%, HR 0.29, 95% CI 0.17 to 0.48), major cardiovascular and cerebrovascular events (4.3% against 5.9%) and heart attack (2.1% against 4.1%). Moderate or severe bleeding rose (2.5% against 1.6%), and death from any cause was 2.0% against 1.5% (HR 1.36, 95% CI 1.00 to 1.85) [6]. Across 10 trials, treatment beyond 12 months lowered heart attack (OR 0.53) and stent thrombosis (OR 0.33) and raised major bleeding (OR 1.62) and death from any cause (OR 1.30, 95% CI 1.02 to 1.66). Courses shorter than 12 months lowered major bleeding (OR 0.58) with no significant difference in ischemic outcomes [7].
Population
9,961 patients after a drug-eluting stent [6]; 32,287 patients in 10 trials [7].
Sources
[6], [7]
Caveats
The large trial tested clopidogrel or prasugrel, not clopidogrel alone, and both groups kept taking aspirin [6]. No trial here compared a stent with no antiplatelet drug.
Moderate

Clopidogrel with aspirin after a minor stroke or TIA

Shown to cut stroke in the next 90 days to 8.2% against 11.7% on aspirin alone after a minor stroke or TIA in one of two trials.

The numbers and sources
Effect
Started within 24 hours of a minor stroke or high-risk transient ischemic attack, clopidogrel plus aspirin lowered stroke at 90 days to 8.2% against 11.7% on aspirin alone (HR 0.68, 95% CI 0.57 to 0.81), with moderate or severe hemorrhage in 0.3% of each group [8]. In a second trial, major ischemic events occurred in 5.0% against 6.5% (HR 0.75, 95% CI 0.59 to 0.95), and major hemorrhage in 0.9% against 0.4% (HR 2.32, 95% CI 1.10 to 4.87) [9].
Population
5,170 patients in China [8]; 4,881 patients at 269 international sites [9].
Sources
[8], [9]
Caveats
Both trials tested a short course begun within a day of the event. The second was stopped early for both benefit and bleeding [9].
Moderate

Aspirin in the first weeks after a stroke or TIA

Shown to cut repeat ischemic stroke in the first 6 weeks by about 60%, with no further benefit seen after 12 weeks.

The numbers and sources
Effect
Across 12 trials, aspirin lowered the 6-week risk of recurrent ischemic stroke (84 of 8,452 against 175 of 7,326, HR 0.42, 95% CI 0.32 to 0.55) and of disabling or fatal ischemic stroke (HR 0.29, 95% CI 0.20 to 0.42). The effects did not depend on dose. After 12 weeks, stroke risk did not differ from control (OR 0.97, 95% CI 0.84 to 1.12) [10].
Population
15,778 participants in 12 trials of aspirin against control [10].
Sources
[10]
Caveats
A pooled time-course analysis of older trials.
Moderate

Stroke prevention in atrial fibrillation

Shown to cut stroke by about 22% against no treatment in atrial fibrillation, less than warfarin or apixaban did in direct comparisons.

The numbers and sources
Effect
Across eight trials, antiplatelet agents lowered stroke by 22% (95% CI 6 to 35) against control in nonvalvular atrial fibrillation. Adjusted-dose warfarin lowered stroke 39% more than antiplatelet therapy (95% CI 22 to 52) [17]. In a trial of people unsuited to warfarin, stroke or systemic embolism occurred at 3.7% a year on aspirin against 1.6% on apixaban (HR 0.45 for apixaban, 95% CI 0.32 to 0.62), with major bleeding at 1.2% against 1.4% a year [18].
Population
4,876 participants in eight antiplatelet trials and 12,963 in 12 trials against warfarin [17]; 5,599 patients [18].
Sources
[17], [18]
Caveats
Neither drug's label read here lists atrial fibrillation as an approved use.
ModerateStudied in pregnancyCommon

Preeclampsia prevention in pregnancy

Shown to cut preeclampsia by about 18% with low-dose aspirin in pregnancy, about 1 fewer case per 61 women treated.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across 60 trials, antiplatelet agents, mostly low-dose aspirin, lowered proteinuric preeclampsia (RR 0.82, 95% CI 0.77 to 0.88, number needed to treat 61), preterm birth before 37 weeks (RR 0.91, 95% CI 0.87 to 0.95) and fetal or neonatal death (RR 0.85, 95% CI 0.76 to 0.95). Postpartum hemorrhage above 500 mL was probably slightly more frequent (RR 1.06, 95% CI 1.00 to 1.12) [19].
Population
40,249 women and their babies in 77 trials [19].
Sources
[19]
Caveats
Not a use on the aspirin label read here, which warns against aspirin in the third trimester. See the pregnancy block below.

Mixed results2

StrongUncommon

Aspirin for people without cardiovascular disease

Mixed results: aspirin cut first cardiovascular events by about 11%, 1 in 265 people, while raising major bleeding by 1 in 210.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Across 13 trials, aspirin lowered the composite cardiovascular outcome (HR 0.89, 95% credible interval 0.84 to 0.95, absolute reduction 0.38%, number needed to treat 265) and raised major bleeding (HR 1.43, 95% credible interval 1.30 to 1.56, absolute increase 0.47%, number needed to harm 210) [11]. An earlier individual-data analysis found serious vascular events at 0.51% a year on aspirin against 0.57% on control, with no difference in vascular death (0.19% against 0.19%) [2]. Of the three 2018 trials, one in adults aged 70 or over found no significant drop in cardiovascular disease (HR 0.95, 95% CI 0.83 to 1.08) [12], one in moderate-risk adults found events in 4.29% against 4.48% (HR 0.96, 95% CI 0.81 to 1.13) [13], and one in diabetes found serious vascular events in 8.5% against 9.6% (rate ratio 0.88, 95% CI 0.79 to 0.97) with major bleeding in 4.1% against 3.2% [14]. In 2022 the US Preventive Services Task Force concluded that the net benefit in adults aged 40 to 59 with a 10-year cardiovascular risk of 10% or more is small, and advised against starting low-dose aspirin for primary prevention at age 60 or older [15].
Population
164,225 participants in 13 trials, median age 62 [11]; primary prevention trials with individual participant data [2]; 19,114 adults aged 70 or over [12]; 12,546 moderate-risk adults [13]; 15,480 adults with diabetes [14].
Sources
[11], [2], [12], [13], [14], [15]
Caveats
The band above is the number needed to treat of 265. The trial in diabetes concluded that the absolute benefits were largely counterbalanced by bleeding [14]. Only one guideline body's statement was read for this page.
Moderate

Colorectal cancer

Mixed results: 20-year follow-up of older trials found fewer colon cancers on aspirin, while recent trials found no drop or more cancer deaths.

The numbers and sources
Effect
In 20-year follow-up of four trials, allocation to aspirin lowered colon cancer incidence (HR 0.76, 95% CI 0.60 to 0.96) and mortality (HR 0.65, 95% CI 0.48 to 0.88), and not rectal cancer (HR 0.90, 95% CI 0.63 to 1.30) [20]. In adults with diabetes followed a mean 7.4 years, gastrointestinal tract cancer occurred in 2.0% of each group [14]. In healthy adults aged 70 or over, cancer-related death occurred in 3.1% on aspirin against 2.3% on placebo (HR 1.31, 95% CI 1.10 to 1.56) [21]. The US Preventive Services Task Force stated in 2022 that the evidence is unclear on whether aspirin reduces colorectal cancer incidence or mortality [15].
Population
14,033 patients in four trials, median follow-up 18.3 years [20]; 15,480 adults with diabetes [14]; 19,114 adults aged 70 or over [21].
Sources
[20], [14], [21], [15]
Caveats
Not an approved use. The authors of the trial in older adults called their cancer finding unexpected [21].

Not shown to help1

Limited

Healthy life span in adults over 70

One trial found daily aspirin did not lengthen survival free of dementia or disability in healthy adults aged 70 or over.

The numbers and sources
Effect
Over a median 4.7 years, death, dementia or persistent physical disability occurred at 21.5 events per 1,000 person-years on aspirin 100 mg and 21.2 on placebo (HR 1.01, 95% CI 0.92 to 1.11). Major hemorrhage occurred in 3.8% against 2.8% (HR 1.38, 95% CI 1.18 to 1.62) [16].
Population
19,114 community-dwelling adults in Australia and the US, median age 74, without cardiovascular disease, dementia or disability [16].
Sources
[16]
Caveats
The trial was stopped at a median 4.7 years. Adherence was about 62% in the final year [16].
Why limited
This rests on one trial, of 19,114 people. Strength counts independent studies that agree, so one trial is limited at any size.

Doses studied

The clopidogrel label gives 75 mg once daily, with a single 300 mg loading dose in acute coronary syndromes [22]. The trials above used the same doses [4][8]. The prescription aspirin label gives 162.5 mg once daily [23]. A collaborative meta-analysis found that aspirin 75 to 150 mg a day lowered vascular events at least as much as higher daily doses, with less certainty below 75 mg [1]. The 2018 primary prevention trials in older adults and in diabetes used 100 mg a day [12][14], and the large preeclampsia trials used 50 to 150 mg, most often 60 mg [19].

In 15,076 people with cardiovascular disease, death, heart attack or stroke did not differ between aspirin 81 mg and 325 mg a day (7.28% against 7.51%, HR 1.02, 95% CI 0.91 to 1.14), and 41.6% of those assigned 325 mg switched dose [24].

Risks

Reported risks17

StrongCommon

Major bleeding on aspirin

Shown to raise major bleeding by about 43% against no aspirin, to 4.1% against 3.2% over 7.4 years in one trial and 3.8% against 2.8% in another.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across 13 primary prevention trials, aspirin raised major bleeding (HR 1.43, 95% credible interval 1.30 to 1.56, absolute increase 0.47%, number needed to harm 210) [11]. Major gastrointestinal and extracranial bleeds occurred at 0.10% a year on aspirin against 0.07% on control [2]. Major bleeding occurred in 4.1% on aspirin against 3.2% on placebo over a mean 7.4 years in adults with diabetes [14], and major hemorrhage in 3.8% against 2.8% over a median 4.7 years in adults aged 70 or over [16]. The prescription aspirin label states that aspirin increases the risk of bleeding [23].
Population
164,225 participants in 13 trials [11]; 15,480 adults with diabetes [14]; 19,114 adults aged 70 or over [16].
Sources
[11], [2], [14], [16], [23]
Caveats
The main risk factors for coronary disease were also risk factors for bleeding [2].
ModerateCommon

Bleeding when clopidogrel and aspirin are taken together

Shown to raise major bleeding when clopidogrel was added to aspirin, 3.7% against 2.7% in acute coronary syndromes, and about 60% more with courses beyond a year.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
With clopidogrel added to aspirin, major bleeding occurred in 3.7% against 2.7% on aspirin alone, life-threatening bleeding in 2.2% against 1.8% and minor bleeding in 5.1% against 2.4% [4][22]. After a minor stroke, major hemorrhage occurred in 0.9% against 0.4% [9]. Continuing a thienopyridine with aspirin beyond a year after a stent raised moderate or severe bleeding to 2.5% against 1.6% [6], and across 10 trials extended treatment raised major bleeding (OR 1.62, 95% CI 1.26 to 2.09) and death from any cause (OR 1.30, 95% CI 1.02 to 1.66) [7]. The label states that giving antiplatelet agents together increases bleeding through an additive effect [22].
Population
12,562 patients with acute coronary syndromes [4]; 4,881 patients after minor stroke or TIA [9]; 9,961 patients after a stent [6]; 32,287 patients in 10 trials [7].
Sources
[4], [22], [9], [6], [7]
Caveats
In two short-course trials, major bleeding did not rise (0.58% against 0.55%, and 0.3% against 0.3%) [5][8].
ModerateCommon

Bleeding with warfarin, DOACs and other anticoagulants

Shown to raise major bleeding when aspirin was combined with low-dose rivaroxaban, 3.1% against 1.9% on aspirin alone. Labels warn of the same with warfarin.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In stable vascular disease, major bleeding occurred in 3.1% on rivaroxaban plus aspirin against 1.9% on aspirin alone (HR 1.70, 95% CI 1.40 to 2.05) [29]. Among people on anticoagulants for venous clots, clinically relevant bleeding occurred at 36.6 per 100 patient-years during aspirin use against 16.9 without (HR 1.70, 95% CI 1.38 to 2.11) [30]. The clopidogrel label states that warfarin taken with clopidogrel increases the risk of bleeding through independent effects on clotting [22], and the aspirin label lists anticoagulants as increasing the risk of bleeding [23].
Population
27,395 participants with stable atherosclerotic vascular disease [29]; 8,246 patients treated for venous clots [30].
Sources
[29], [30], [22], [23]
Caveats
The second analysis is observational within trials and gives rates per patient-years [30].
ModerateCommon

Stopping treatment

Linked to about 37% more cardiovascular events after long-term users stopped low-dose aspirin, about one extra event a year per 74 people who stopped.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In a Swedish national cohort, long-term users who stopped low-dose aspirin without major surgery or bleeding had more cardiovascular events than those who continued (adjusted HR 1.37, 95% CI 1.34 to 1.41), equal to one additional event a year in 1 of every 74 people who stopped. The risk rose shortly after stopping [32]. The clopidogrel label states that discontinuation increases the risk of cardiovascular events [22]. After a stent, stent thrombosis and heart attack rose in the 3 months after a thienopyridine was stopped, in both trial groups [6].
Population
Long-term low-dose aspirin users in Swedish registers, followed a median 3.0 years with 62,690 cardiovascular events [32]; 9,961 patients after a stent [6].
Sources
[32], [22], [6]
Caveats
The cohort is observational, and people who stop may differ from those who continue.
LimitedCommon

Death from any cause in healthy older adults on aspirin

One trial found more deaths on aspirin than placebo in healthy adults aged 70 or over, driven by cancer deaths in 3.1% against 2.3%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Over a median 4.7 years, death from any cause occurred at 12.7 events per 1,000 person-years on aspirin against 11.1 on placebo (HR 1.14, 95% CI 1.01 to 1.29). Cancer-related death occurred in 3.1% against 2.3% (HR 1.31, 95% CI 1.10 to 1.56) [21]. In moderate-risk adults followed a median 60 months, deaths were 2.55% on aspirin and 2.57% on placebo [13].
Population
19,114 healthy adults aged 70 or over [21]; 12,546 moderate-risk adults [13].
Sources
[21], [13]
Caveats
The authors called the result unexpected in the context of earlier studies and urged caution in interpreting it [21]. A second trial found no difference in deaths [13].
Why limited
This rests on one trial, of 19,114 people. Strength counts independent studies that agree, so one trial is limited at any size.
ModerateUncommon

Stomach and gut bleeding and ulcers

Shown to about double stomach and gut bleeding on aspirin, 0.97% against 0.46% on placebo over five years in one trial.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In moderate-risk adults, gastrointestinal bleeding, mostly mild, occurred in 0.97% on aspirin against 0.46% on placebo over a median 60 months (HR 2.11, 95% CI 1.36 to 3.28) [13]. In a head-to-head trial, gastrointestinal hemorrhage occurred in 2.0% on clopidogrel against 2.7% on aspirin, and bleeding needing hospitalization in 0.7% against 1.1% [22]. The prescription aspirin label states that aspirin may cause gastric ulceration and bleeding, with particular risk in people with a history of peptic ulcer [23]. In people on aspirin and clopidogrel, gastrointestinal events occurred in 2.9% on placebo against 1.1% on omeprazole [28].
Population
12,546 moderate-risk adults [13]; 19,185 patients in the clopidogrel against aspirin trial [22][3]; 3,761 patients on both drugs [28].
Sources
[13], [22], [3], [23], [28]
Caveats
The band above is the 0.97% in the placebo-controlled trial. The head-to-head rates have no placebo group.
ModerateUncommon

Bleeding in the brain

Shown to raise hemorrhagic stroke slightly on aspirin, 0.04% against 0.03% a year, with intracranial bleeding in 0.4% to 0.5% on either drug over two years.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In primary prevention trials, hemorrhagic stroke occurred at 0.04% a year on aspirin against 0.03% on control [2]. In the head-to-head trial, intracranial hemorrhage occurred in 0.4% on clopidogrel and 0.5% on aspirin [22]. With clopidogrel added to aspirin in acute coronary syndromes, intracranial hemorrhage occurred in 0.1% of each group [22].
Population
Primary prevention trials with individual participant data [2]; 19,185 patients followed a mean 1.91 years [3]; 12,562 patients [4].
Sources
[2], [22], [3], [4]
Caveats
The primary prevention difference was of borderline significance (p=0.05) [2].
LimitedUncommon

Rash and diarrhea on clopidogrel

One trial found severe rash in 0.26% on clopidogrel against 0.10% on aspirin, and severe diarrhea in 0.23% against 0.11%.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Adverse experiences judged severe included rash (0.26% on clopidogrel against 0.10% on aspirin), diarrhea (0.23% against 0.11%) and upper gastrointestinal discomfort (0.97% against 1.22%). A significant fall in neutrophils occurred in 0.10% on clopidogrel and 0.17% on aspirin [3].
Population
19,185 patients followed a mean 1.91 years [3].
Sources
[3]
Caveats
The comparator is aspirin 325 mg, not placebo. Only events judged severe are counted.
Why limited
This rests on one trial, of 19,185 people. Strength counts independent studies that agree, so one trial is limited at any size.
LimitedHow often is not known

NSAIDs, including ibuprofen blocking aspirin's effect

The labels warn that NSAIDs raise the risk of bleeding with either drug. A small study found ibuprofen taken before aspirin blocked aspirin's effect on platelets.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The clopidogrel label states that NSAIDs taken with clopidogrel increase the risk of gastrointestinal bleeding [22]. The aspirin label states that other NSAIDs increase the risk of bleeding and may impair kidney function, and that ibuprofen can interfere with the antiplatelet effect of low-dose aspirin [23]. In a crossover study, aspirin's inhibition of platelet thromboxane and aggregation was blocked when a single daily dose of ibuprofen was given before aspirin and when ibuprofen was given several times a day. Rofecoxib, acetaminophen and diclofenac did not have this effect [31].
Population
Statements in labeling [22][23]; volunteers in a crossover pharmacodynamic study [31].
Sources
[22], [23], [31]
Caveats
The ibuprofen study measured platelet function, not heart attacks or strokes. The labels give no rates.
LimitedHow often is not known

SSRI and SNRI antidepressants with clopidogrel

The label states that SSRI and SNRI antidepressants affect platelet activation and may increase the risk of bleeding when taken with clopidogrel. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The clopidogrel label states that because selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors affect platelet activation, taking them with clopidogrel may increase the risk of bleeding [22].
Population
A statement in labeling, with no study counts [22].
Sources
[22]
Caveats
The label gives no numbers.
LimitedHow often is not known

Opioids and clopidogrel absorption

The label states that opioids delay and reduce the absorption of clopidogrel, lowering exposure to its active metabolites. It gives no outcome rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The clopidogrel label states that opioid agonists such as morphine delay and reduce the absorption of clopidogrel, presumably through slowed stomach emptying, resulting in reduced exposure to its metabolites [22].
Population
Interaction data summarized in labeling [22].
Sources
[22]
Caveats
A change in drug exposure, with no rate of clots given.
LimitedHow often is not known

Clopidogrel raising levels of repaglinide

The label states that a clopidogrel metabolite strongly inhibits the enzyme CYP2C8 and can raise blood levels of the diabetes drug repaglinide.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The clopidogrel label states that its acyl-beta-glucuronide metabolite is a strong inhibitor of CYP2C8, and that clopidogrel can increase exposure to drugs cleared mainly by that enzyme, naming repaglinide [22].
Population
Interaction data summarized in labeling [22].
Sources
[22]
Caveats
The label section read here gives no rate of low blood sugar.
LimitedHow often is not known

Kidney function and blood pressure medicines with aspirin

The aspirin label warns that NSAIDs including aspirin taken with ACE inhibitors or similar drugs may worsen kidney function in older or dehydrated people.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The prescription aspirin label states that in people who are elderly, volume-depleted, including those on diuretics, or who have compromised kidney function, NSAIDs including aspirin taken with renin-angiotensin system inhibitors may result in deterioration of kidney function, including possible acute kidney failure, usually reversible. It also states that NSAIDs may weaken the blood pressure lowering effect of these drugs [23].
Population
A class statement in labeling, with no study counts [23].
Sources
[23]
Caveats
The label gives no rate and does not separate low-dose aspirin from other NSAIDs.
LimitedHow often is not known

Thrombotic thrombocytopenic purpura on clopidogrel

The label warns of thrombotic thrombocytopenic purpura, sometimes fatal, after clopidogrel, in some cases within two weeks of starting. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The clopidogrel label states that thrombotic thrombocytopenic purpura, sometimes fatal, has been reported, sometimes after less than 2 weeks of exposure, and describes low platelets, red cell breakdown, neurological findings, kidney dysfunction and fever. Postmarketing reports also include agranulocytosis and aplastic anemia [22].
Population
Postmarketing reports summarized in labeling [22].
Sources
[22]
Caveats
Reports with no denominator.
LimitedHow often is not known

Aspirin-sensitive asthma and allergic reactions

The label warns that aspirin may cause severe hives, swelling or bronchospasm in people with the syndrome of asthma, rhinitis and nasal polyps.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The prescription aspirin label lists hypersensitivity to NSAIDs and the syndrome of asthma, rhinitis and nasal polyps as contraindications, stating that aspirin may cause severe urticaria, angioedema or bronchospasm [23].
Population
A contraindication in labeling, with no study counts [23].
Sources
[23]
Caveats
The label gives no rate.
LimitedHow often is not known

Liver reactions and Reye's syndrome on the aspirin label

The aspirin label lists indigestion, raised liver enzymes, hepatitis and Reye's syndrome among adverse reactions. It gives no rates.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The prescription aspirin label lists dyspepsia, hepatic enzyme elevation, hepatitis and Reye's syndrome among gastrointestinal adverse reactions. It also states that salicylate can reduce kidney clearance of methotrexate, leading to bone marrow toxicity, and can change blood levels of phenytoin and valproic acid [23].
Population
Reports summarized in labeling [23].
Sources
[23]
Caveats
The label gives no frequencies and covers aspirin at all doses.
LimitedStudied in pregnancyHow often is not known

Pregnancy

The aspirin label warns that aspirin late in pregnancy can harm the fetus. Trials of low-dose aspirin found slightly more bleeding after birth.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The prescription aspirin label states that maternal aspirin use in later pregnancy may cause low birth weight, intracranial hemorrhage in premature infants, stillbirth and neonatal death, and that NSAIDs may cause premature closure of the fetal ductus arteriosus in the third trimester [23]. In trials of low-dose aspirin to prevent preeclampsia, postpartum hemorrhage above 500 mL was probably slightly more frequent (RR 1.06, 95% CI 1.00 to 1.12), while fetal or neonatal death was less frequent (RR 0.85) [19]. The clopidogrel label states that published cases and postmarketing surveillance have not identified drug-associated risks of major birth defects or miscarriage [22].
Population
Statements in labeling [23][22]; 40,249 women in 77 trials [19].
Sources
[23], [19], [22]
Caveats
The label warning covers aspirin at all doses, and the trials used low doses. The sources do not give the share of pregnancies affected.

Mixed results2

ModerateCommon

FDA boxed warning: weaker effect of clopidogrel in CYP2C19 poor metabolizers

FDA states clopidogrel has a reduced effect on platelets in people with two loss-of-function CYP2C19 alleles. Studies disagree on how far outcomes differ.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The boxed warning states that clopidogrel depends on conversion to an active metabolite, mainly by CYP2C19, that it forms less of this metabolite in people with two nonfunctional alleles, and that tests can identify them [22]. In a meta-analysis of people treated mostly for stenting, 2.2% carried two reduced-function alleles and 26.3% one. Carriers of one or two had more cardiovascular death, heart attack or stroke (HR 1.55 and 1.76) and more stent thrombosis (HR 2.67 and 3.97) than noncarriers [25]. A second meta-analysis found a higher risk of cardiovascular events in carriers (RR 1.18, 95% CI 1.09 to 1.28) that disappeared in studies with 200 or more events (RR 0.97, 95% CI 0.86 to 1.09), with evidence of small-study bias [26]. In a trial after stenting, carriers given genotype-guided treatment had events in 4.0% against 5.9% on clopidogrel (HR 0.66, 95% CI 0.43 to 1.02) [27].
Population
9,685 patients, 91.3% of whom had a stent procedure [25]; 42,016 patients in 32 studies [26]; 5,302 patients, 1,849 of them carriers [27].
Sources
[22], [25], [26], [27]
Caveats
The band above is the 2.2% who carried two reduced-function alleles in one pooled population [25]. The trial result did not reach statistical significance [27].
LimitedHow often is not known

Omeprazole and esomeprazole with clopidogrel

The label warns that omeprazole and esomeprazole significantly reduce clopidogrel's antiplatelet activity. One trial found no difference in cardiovascular events with omeprazole.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that omeprazole significantly reduced the antiplatelet activity of clopidogrel when given together or 12 hours apart, that esomeprazole had a similar effect, and that dexlansoprazole, lansoprazole and pantoprazole had less effect [22]. In a trial of people on aspirin and clopidogrel, cardiovascular events occurred in 4.9% on omeprazole and 5.7% on placebo (HR 0.99, 95% CI 0.68 to 1.44), and gastrointestinal events in 1.1% against 2.9% (HR 0.34, 95% CI 0.18 to 0.63) [28].
Population
Pharmacodynamic studies summarized in labeling [22]; 3,761 patients with coronary artery disease followed to 180 days [28].
Sources
[22], [28]
Caveats
The trial stopped short of its planned enrollment, and its authors state that it does not rule out a meaningful difference in cardiovascular events [28].
Why limited
This rests on one trial, of 3,761 people. Strength counts independent studies that agree, so one trial is limited at any size.

Claims tested and not found

  1. That a daily aspirin lengthens healthy life in older adults. In 19,114 adults aged 70 or over, death, dementia or persistent disability did not differ from placebo (HR 1.01, 95% CI 0.92 to 1.11) [16].
  2. That 325 mg of aspirin protects better than 81 mg. In 15,076 people with cardiovascular disease, death, heart attack or stroke did not differ between the doses (HR 1.02, 95% CI 0.91 to 1.14) [24].
  3. That aspirin lowers cardiovascular death in people without cardiovascular disease. Vascular mortality was 0.19% a year on aspirin and 0.19% on control across primary prevention trials [2].
  4. That omeprazole taken with clopidogrel raises heart attacks and strokes. In 3,761 patients, cardiovascular events did not differ between omeprazole and placebo (HR 0.99, 95% CI 0.68 to 1.44). The authors could not rule out a meaningful difference [28].
  5. That choosing the antiplatelet drug by CYP2C19 genotype improves outcomes after a stent. Among 1,849 carriers, the difference in events at 12 months was not statistically significant (4.0% against 5.9%, HR 0.66, 95% CI 0.43 to 1.02) [27].
  6. That aspirin protects against stroke in atrial fibrillation as well as an anticoagulant. Warfarin lowered stroke 39% more than antiplatelet therapy across 12 trials [17], and apixaban more than halved stroke or systemic embolism against aspirin [18].

Sources

  1. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002. https://doi.org/10.1136/bmj.324.7329.71
  2. Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. The Lancet. 2009. https://doi.org/10.1016/S0140-6736(09)60503-1
  3. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). The Lancet. 1996. https://doi.org/10.1016/S0140-6736(96)09457-3
  4. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. New England Journal of Medicine. 2001. https://doi.org/10.1056/NEJMoa010746
  5. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. The Lancet. 2005. https://doi.org/10.1016/S0140-6736(05)67660-X
  6. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. New England Journal of Medicine. 2014. https://doi.org/10.1056/NEJMoa1409312
  7. Navarese EP, Andreotti F, Schulze V, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015. https://doi.org/10.1136/bmj.h1618
  8. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. New England Journal of Medicine. 2013. https://doi.org/10.1056/NEJMoa1215340
  9. Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1800410
  10. Rothwell PM, Algra A, Chen Z, et al. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. The Lancet. 2016. https://doi.org/10.1016/S0140-6736(16)30468-8
  11. Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA. 2019. https://doi.org/10.1001/jama.2018.20578
  12. McNeil JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1805819
  13. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. The Lancet. 2018. https://doi.org/10.1016/S0140-6736(18)31924-X
  14. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1804988
  15. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication. Final Recommendation Statement. 2022. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication
  16. McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1800722
  17. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Annals of Internal Medicine. 2007. https://doi.org/10.7326/0003-4819-146-12-200706190-00007
  18. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. New England Journal of Medicine. 2011. https://doi.org/10.1056/NEJMoa1007432
  19. Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database of Systematic Reviews. 2019. https://doi.org/10.1002/14651858.CD004659.pub3
  20. Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. The Lancet. 2010. https://doi.org/10.1016/S0140-6736(10)61543-7
  21. McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1803955
  22. U.S. Food and Drug Administration. Plavix (clopidogrel) tablets, prescribing information (Sanofi-Aventis U.S.). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de8b0b67-eb25-4684-83b5-7ad785314227
  23. U.S. Food and Drug Administration. Durlaza (aspirin) extended release capsules, prescribing information (New Haven Pharmaceuticals). 2015. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c2a1403-3862-1efd-0a91-444989222b37
  24. Jones WS, Mulder H, Wruck LM, et al. Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease. New England Journal of Medicine. 2021. https://doi.org/10.1056/NEJMoa2102137
  25. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010. https://doi.org/10.1001/jama.2010.1543
  26. Holmes MV, Perel P, Shah T, Hingorani AD, Casas JP. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis. JAMA. 2011. https://doi.org/10.1001/jama.2011.1880
  27. Pereira NL, Farkouh ME, So D, et al. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA. 2020. https://doi.org/10.1001/jama.2020.12443
  28. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. New England Journal of Medicine. 2010. https://doi.org/10.1056/NEJMoa1007964
  29. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. New England Journal of Medicine. 2017. https://doi.org/10.1056/NEJMoa1709118
  30. Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Internal Medicine. 2014. https://doi.org/10.1001/jamainternmed.2014.946
  31. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. New England Journal of Medicine. 2001. https://doi.org/10.1056/NEJMoa003199
  32. Sundström J, Hedberg J, Thuresson M, et al. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study. Circulation. 2017. https://doi.org/10.1161/CIRCULATIONAHA.117.028321

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