Informed consent-patients' understanding of risk.

AIMS: The central concept of informed consent is communication of the chance of a successful outcome. The risks and benefits are probabilistic concepts derived from populations; they do not map with any certainty to the individual. We tested patients' comprehension of basic probability concepts that are needed for informed consent. METHODS: Patients (n=478) completed five questions designed to test risk estimates that are relevant to informed consent. The questions posed non-medical scenarios to avoid patients associating them with their clinical care. The questionnaire was in English and was only offered to patients whose nurse felt that they had sufficient English literacy to understand the questions. RESULTS: Out of a possible total of five correct answers, Asian patients scored lowest, and significantly less than Pakeha/Europeans (average total score 2.6±1.7 vs 3.6±1.4, p<0.001, 95% confidence interval 0.5 to 1.38). The total score for Maori/Pasifika was intermediate (3.2±1.4), yet they had the lowest deprivation index. This discordant finding may be due to poorer English literacy among Asian participants. On multiple linear regression, Asian ethnicity and advancing age were the independent predictors of a low score. Socio-economic deprivation decile and sex were not. CONCLUSIONS: When answering questions constructed according to best practice, many (but not all) patients have reasonable risk comprehension. Further improvement could target older patients, those of Asian ethnicity and probably all patients where English is a second language. Liberal use of interpreters is suggested.

Signal-to-noise of linear and volume measures of left ventricular and left atrial size.

BACKGROUND: Serial echocardiographic assessments are common in clinical cardiology, e.g., for timing of intervention in mitral and aortic regurgitation. When following patients with serial echocardiograms, each new measurement is a combination of true change and confounding noise. The current investigation compares linear chamber dimensions with volume estimates of chamber size. The aim is to assess which measure is best for serial echocardiograms, when the ideal parameter will be sensitive to change in chamber size and have minimal spurious variation (noise). We present a method that disentangles true change from noise. Linear regression of chamber size against elapsed time gives a slope, being the ability of the method to detect change. Noise is the scatter of individual points away from the trendline, measured as the standard error of the slope. The higher the signal-to-noise ratio (SNR), the more reliably a parameter will distinguish true change from noise. METHODS: LV and LA parasternal dimensions and apical biplane volumes were obtained from serial clinical echocardiogram reports. Change over time was assessed as the slope of the linear regression line, and noise was assessed as the standard error of the regression slope. Signal-to-noise ratio is the slope divided by its standard error. RESULTS: The median number of LV studies was 5 (4-11) for LV over a mean duration of 5.9 ± 3.0 years in 561 patients (diastole) and 386 (systole). The median number of LA studies was 5 (4-11) over a mean duration of 5.3 ± 2.0 years in 137 patients. Linear estimates of LV size had better signal-to-noise than volume estimates (p < 0.001 for diastolic and p = 0.035 for systolic). For the left atrium, the difference was not significant (p = 0.214). This may be due to sample size; the effect size was similar to that for LV systolic size. All three parameters had a numerical value of signal-to-noise that favoured linear dimensions over volumes. CONCLUSION: Linear measures of LV size have better signal-to-noise than volume measures. There was no difference in signal-to-noise between linear and volume measures of LA size, although this may be a Type II error. The use of regression lines may be better than relying on single measurements. Linear dimensions may clarify whether changes in volumes are real or spurious.

Hospitalisation during lockdown-patients' beds-eye views.

AIMS: The global COVID-19 pandemic and lockdowns have affected the patterns of hospital presentations for non-COVID related illnesses. Apprehension and perceived risk of hospitalisation has been postulated to be a significant deterrent to presentation. This study aims to explore pandemic- and- lockdown-related concerns with regards to hospital admission from a patient's perspective. METHODS: A cross-sectional study was undertaken in the form of an inpatient questionnaire for patients admitted to a coronary care unit and the cardiology ward during the Level 4 lockdown. The questionnaire included six questions designed to gather patient perception of the impact of lockdown on their hospital presentation. RESULTS: Out of 91 patients who completed the questionnaire, 41 (45%) were >70 years old. Twenty (22%) patients answered that lockdown delayed or affected their decision to present to hospital. Within this cohort, there was a statistical difference between those aged 70 years and younger, and those over 70 years old (16/50 (32%) versus 4/41 (10%), p=0.011). CONCLUSIONS: Apprehension and concerns regarding the risk of COVID-19 was prevalent in a significant proportion of patients and affected/delayed their decision to present to hospital. This may partly explain lower rates of presentation during the pandemic.

A Decade of Transcatheter Aortic Valve Implantation in New Zealand: Growth and Inequalities.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an effective treatment increasingly performed for severe aortic stenosis. Developing nationwide accessibility to TAVI can be met with barriers that result in treatment disparities. OBJECTIVES: This nationwide retrospective study aimed to review the first decade of TAVI in New Zealand and identify potential inequalities. METHODS: All patients undergoing TAVI in a New Zealand public hospital between 2008 and 2018 were included. Demographic and geographic details were analysed and TAVI rates were age standardised using census data. One-year survival was compared between groups. RESULTS: A total of 952 patients were included in our study. The mean age was 80.0±7.5 years and women accounted for nearly half of all patients (42.5%). The age-standardised TAVI rate in New Zealand increased from 15 per million in 2013 to 49 per million in 2018. Since 2013, there has been a disproportionate growth in TAVI rates between different ethnicities. TAVI rates for Europeans grew from 16 to 66 per million compared to 7 to 8 per million for Pacific people and 3 to 5 per million for Maori. Despite nationwide access to TAVI in 2018, significant geographic heterogeneity remains, ranging from 2.0 to 12.8 procedures per 100,000 people between regions. One-year (1-yr) survival for Maori were significantly worse than Europeans (80.1% vs 93.9%, HR 4.2, 95%CI: 1.6-11.5, p=0.004) despite being younger (67.9 vs 80.6 years, p<0.05). CONCLUSION: There are significant geographical and ethnic variations in TAVI rates in New Zealand. Maori had worse one-year survival than European patients following TAVI.

Calcified Coronary Lesions Treated With Intravascular Lithotripsy: One-Year Outcomes.

Calcified lesions often increase the complexity of percutaneous coronary intervention (PCI) and risk of future adverse events. Shockwave intravascular lithotripsy (S-IVL; Shockwave Medical) has been shown to be an effective calcium-modification tool in preparing calcified coronary lesions prior to stent placement. Its circumferential, pulsatile soundwaves provide a different mechanism to fracture calcium compared with existing devices such as rotational atherectomy and cutting balloons. Although short-term safety outcomes have been positive, longer-term outcomes have yet to be reported. We previously described the first real-world series of PCI involving S-IVL, including use in acute coronary syndromes and left main interventions. We report the 1-year outcomes of patients treated with S-IVL during their PCI.

Empagliflozin-Mediated Lithium Excretion: A Case Study and Clinical Applications.

BACKGROUND Empagliflozin selectively reduces apical sodium-glucose co-transporter 2 function in the proximal convoluted tubules, increasing sodium and glucose excretion in the urine, ultimately reducing glucose reabsorption in the kidneys for diabetic management. Lithium, the gold-standard treatment for bipolar disorder, also utilizes sodium transporters in the proximal convoluted tubules. CASE REPORT Presenting with a manic relapse of refractory schizoaffective disorder, our patient was found to have subtherapeutic levels of lithium on admission due to poor outpatient medication compliance. Restoration to therapeutic lithium levels allowed inpatient blood glucose measurements, which led to a new diagnosis of type 2 diabetes mellitus. Given his comorbid severe hepatic impairment, obesity, and prior pancreatitis, the patient was started on empagliflozin to safely manage this new diagnosis without collateral organ injury. Routine monitoring found reproducible and clinically significant decreases in serum lithium levels in the presence of empagliflozin therapy, without obvious confounding factors. Subsequent discussion with specialist teams resulted in trialling metformin, which adequately controlled the new diabetic diagnosis without inpatient complications. CONCLUSIONS We suspect that empagliflozin reduced sodium-glucose and lithium-glucose reabsorption in the proximal connecting tubules, thereby increasing the renal excretion of sodium, glucose, and lithium. Applications include awareness of the interaction between these medications, support for the role of physiological SGLT-2-mediated lithium transport, and the possibility of using empagliflozin and other SGLT-2 inhibitors to treat life-threatening lithium toxicity.

Nonbacterial thrombotic endocarditis of a bioprosthetic valve: Questions to ponder before replacement of the valve.

Nonbacterial thrombotic endocarditis (NBTE) of bioprosthetic valves is extremely rare. We report a 67-year-old lady with early bioprosthetic "failure" that at reoperation was proven to be NBTE. The choice of a prosthesis in this condition may have implications for patients' late clinical course.

Treatment of Heavily Calcified Unprotected Left Main Disease With Lithotripsy: The First Case Series.

We present the first case series using Shockwave Intravascular Lithotripsy (S-IVL; Shockwave Medical), a novel coronary calcium modification device, in patients with heavily calcified unprotected left main (LM) coronary artery disease (CAD). Decisions regarding surgical vs percutaneous revascularization in LM-CAD patients are based on anatomical complexity and perceived surgical risk. In this series, we present the use of S-IVL in a patient with LM-CAD with multivessel disease who declined surgery, a patient with an isolated LM-CAD and severe cardiomyopathy, and a late nonagenarian patient where surgical revascularization was not an option.

Associations between the home yard and preschoolers' outdoor play and physical activity.

Objectives and importance of study: Young children's outdoor play mostly occurs within the home-yard space, yet the influence of the home yard on preschoolers' outdoor play and physical activity is poorly understood. We investigated the relationships between home-yard features and home-based outdoor play and physical activity in preschoolers (2-5 years old). STUDY TYPE: Cross-sectional observational study. METHODS: The PLAY Spaces and Environments for Children's Physical Activity (PLAYCE) study (2015-2017) included 1596 children aged 2-5 years attending early childhood education and care (ECEC) services throughout metropolitan Perth, Western Australia. In this study, a subsample of 224 parents from the PLAYCE study completed an online questionnaire about home-yard features (yard size, lawn quality, natural features, fixed and portable play equipment, and flowers and vegetables/herbs). Accelerometers measured the duration of preschoolers' moderate-vigorous physical activity (MVPA) on non-ECEC days. Parent-reported outdoor play at home, sociodemographic factors and social environment factors were collected via the PLAYCE parent survey. Multiple linear regression models were used to determine associations between home-yard features and preschoolers' outdoor play and physical activity. RESULTS: Children spent 68.9 (SD 2.2) minutes playing outdoors in the home yard per day, and 93.3 (SD 37.1) minutes in MVPA per day on non-ECEC days. After adjusting for child and parent factors, home-yard features positively associated with outdoor play included yard size, lawn quality, number of types of fixed and portable play equipment, natural features and play areas (all p ≤ 0.05). When all significant home-yard features were placed in a model, only the number of types of fixed play equipment was positively associated with minutes of outdoor play per day (ß = 5.3, p < 0.001). After adjusting for sociodemographic factors, the number of types of portable play equipment in the yard was positively associated with MVPA minutes per day (ß = 2.16, p = 0.019); however, this became nonsignificant after further adjusting for social environment factors. CONCLUSIONS: Features of the home-yard physical environment were positively associated with preschoolers' outdoor play and physical activity. Each additional type of fixed play equipment present was associated with an additional 5 minutes of outdoor play per day. These findings suggest that the home-yard space has the potential to facilitate increased outdoor play in young children. Further research is warranted to explore causal relationships between home-yard attributes and young children's outdoor play and physical activity.

Shockwave Intravascular Lithotripsy of Calcified Coronary Lesions in ST-Elevation Myocardial Infarction: First-in-Man Experience.

We present the first cases of Shockwave intravascular lithotripsy (S-IVL; Shockwave Medical), a novel coronary calcium modification device, being used in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI). The 3 presented cases include an upfront use of S-IVL in a right coronary artery, an in-stent restenosis, and a community cardiac arrest/STEMI equivalent where S-IVL was used as a bail-out technique to facilitate stent delivery in a tortuous calcified vessel.

Shockwave Intravascular Lithotripsy for Calcified Coronary Lesions: First Real-World Experience.

BACKGROUND: Calcified coronary lesions often cause suboptimal stent expansion, which is one of the greatest predictors of adverse outcomes such as stent thrombosis and restenosis. Shockwave intravascular lithotripsy (S-IVL; Shockwave Medical, Inc) is a recently approved technique used in the treatment of heavily calcified coronary lesions. We present our early real-world experience with the S-IVL device. METHODS: All patients treated with S-IVL between October 2018 and January 2019 during their percutaneous coronary intervention (PCI) at our center were included. RESULTS: During this period, a total of 26 patients undergoing PCI were treated with S-IVL prior to stent deployment (69% male; age, 72 ± 8 years). Indications for PCI were acute coronary syndromes (ACS) in 14 patients (54%), stable angina in 11 patients (42%), and PCI before transcatheter aortic valve implantation in 1 patient (4%). Seventy-one percent of the ACS cases undergoing PCI with S-IVL were to the perceived ACS culprit lesion during the index procedure, while 29% were staged PCIs to severe non-culprit lesions. Upfront S-IVL usage occurred in 58% of cases; the rest were bail-out procedures due to suboptimal initial balloon predilation. S-IVL was used most commonly in the left anterior descending coronary artery (50%), with 1.3 ± 0.5 stents implanted/target vessel. Angiographic success (<20% residual stenosis) occurred in all cases, with no procedural complications. CONCLUSION: S-IVL appears to be a useful modality in coronary calcium modification to optimize stent expansion. This device obviates the need for more complex lesion preparation strategies such as rotational atherectomy, except in severe undilatable cases where S-IVL is impossible. Further study is warranted to compare different calcium modification devices with conventional balloon angioplasty.

A review of a regional primary percutaneous coronary intervention service, with a focus on door to reperfusion times: the 2012 Auckland/Northland experience.

AIMS: Primary percutaneous coronary intervention (PCI) is the optimal management for ST segment elevation myocardial infarction (STEMI) patients. We reviewed the largest primary PCI regional service in New Zealand: the Auckland/Northland service based at Auckland City Hospital, to assess patient management, in particular the door to reperfusion times (DTRTs), and predictors of death in hospital. METHODS: We obtained patient details from a comprehensive prospective database of all primary PCI patients admitted with STEMI from 1/1/12 to 31/12/12 to the Auckland City Hospital cardiac catheterisation laboratory. Of four District Health Boards (DHBs) within the region, two accessed this regional service at all times, and two accessed the Auckland City Hospital cardiac catheterisation laboratory 'after hours': all times except for 08:00 to 16:00 hours on Monday to Friday. RESULTS: A total of 401 adult patients underwent a primary PCI at the Auckland City Hospital Regional centre for a STEMI presentation, over the 12 months period. The median patient age was 61 years, 77% were male. Overall 183 (46%) (95% CI 41, 51) patients achieved a DTRT of < 90 mins, and 266 (66%) (95% CI 61, 71) a DTRT of < 120 mins, with a clear geographical influence to these times. Of 27 patients with direct transfer to the catheter laboratory from the community, the DTRT was < 120 mins in 24 (92%) (95% CI 72, 96) patients. In-hospital mortality was 24 (6%) patients (95% CI 4, 9). CONCLUSIONS: The 2012 Auckland/Northland primary PCI service delivers good outcomes consistent with current Australasian standards. Although geographical isolation complicates door to reperfusion times, these may potentially be improved by more focus on direct transfer to the cardiac catheterisation laboratory, especially directly from the community.

An uncommon cause of myocardial infarction.

A 73 year-old lady with hypertension and chronic atrial fibrillation (AF) developed chest pain followed by ventricular fibrillation (VF) cardiac arrest. Her electrocardiogram post-cardioversion revealed inferior ST-elevation myocardial infarction (MI). Her coronary arteries were angiographically normal. Contrast-enhanced cardiac magnetic resonance(CE-CMR) demonstrated both an inferior subendocardial infarction and left atrial (LA) appendage thrombus suggesting cardioembolism as the most likely cause of her presentation.

Prevalence and prognostic significance of left ventricular dysfunction in patients presenting acutely with atrial fibrillation.

CONDENSED ABSTRACT: The prevalence and prognostic importance of CM occurring as a consequence of AF is poorly defined. This study investigated the incidence of CM in patients with AF, its clinical features and long-term outcomes. We demonstrated that CM is common in patients presenting acutely with newly diagnosed rapid AF, and carries a worse long-term prognosis. Systolic dysfunction was reversible in an important proportion of patients, suggesting a greater prevalence of rate-related CM in AF than has previously been postulated. This underscores the importance of appropriate rhythm management strategies and repeat imaging studies. BACKGROUND: Atrial fibrillation (AF) may precipitate LV dysfunction, potentially leading to cardiomyopathy (CM). The prevalence and prognostic importance of CM occurring as a consequence of AF is poorly defined. We investigated the incidence of CM in patients with AF, its clinical features and long-term outcomes. METHODS: We reviewed 292 consecutive patients (average age 72 +/- 13yrs) presenting acutely with AF and tachycardia over a 3 year period from June 2004. Clinical details were obtained from medical records. CM was defined as ejection fraction (EF)

Characteristics and prognostic importance of myocardial fibrosis in patients with dilated cardiomyopathy assessed by contrast-enhanced cardiac magnetic resonance imaging.

INTRODUCTION: Dilated cardiomyopathy (DCM) is associated with significant morbidity and mortality. Contrast-enhanced cardiac MRI (CE-CMR) can detect potentially prognostic myocardial fibrosis in DCM. We investigated the role of CE-CMR in New Zealand patients with DCM, both Maori and non-Maori, including the characteristics and prognostic importance of fibrosis. METHODS: One hundred and three patients (mean age 58 ± 13, 78 male) referred for CMR assessment of DCM were followed for 660 ± 346 days. Major adverse cardiac events (MACE) were defined as death, infarction, ventricular arrhythmias or rehospitalisation. CE-CMR used cines for functional analysis, and delayed enhancement to assess fibrosis. RESULTS: Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). Volumetric parameters were similar in patients with or without fibrosis. At 2 years patients with fibrosis had an increased rate of MACE (HR = 0.77, 95% CI 0.3-2.0). Patients with full thickness or subendocardial fibrosis had the highest MACE, even in the absence of CAD). More Maori had fibrosis on CE-CMR (40% vs. 28% for non-Maori), and the majority (75%) was mid-myocardial. Maori and non-Maori had similar outcomes (25% vs. 24% with events during follow-up). CONCLUSIONS: DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial. Fibrosis is associated with worse outcome in the medium term. The information obtained using CE-CMR in DCM may be of incremental clinical benefit.

Noncardiac surgery and bleeding after percutaneous coronary intervention.

BACKGROUND: The decision on whether to implant a drug-eluting or bare-metal stent during percutaneous coronary intervention (PCI) depends in part on the perceived likelihood of the patient developing late stent thrombosis. Noncardiac surgery and bleeding are associated with discontinuation of dual antiplatelet therapy and with increased stent thrombosis. We assessed the incidence of and predictors for subsequent noncardiac surgery and bleeding episodes in patients who had undergone PCI. METHODS AND RESULTS: Hospital discharge coding data were used to identify all adult patients undergoing public hospital PCI in New Zealand from 1996 to 2001. Hospital admissions during the ensuing 5 years were analyzed for noncardiac surgery and bleeding episodes. Eleven thousand one hundred fifty-one patients (age, 62+/-11 years; 30% women) underwent PCI, mainly for an acute coronary syndrome (73%). During the 5-year follow-up, 26% of the population underwent at least 1 noncardiac surgical procedure (23% orthopedic, 20% abdominal, 12% urologic, 10% vascular, 35% others) and 8.6% had at least 1 bleeding episode either requiring or occurring during hospitalization. Of those, half were gastrointestinal, and one quarter of bleeding events required blood transfusion. The main clinical predictors of noncardiac surgery were advanced age, previous noncardiac surgery, osteoarthritis, and peripheral vascular disease. A previous bleeding admission and age were the strongest predictors of subsequent bleeding. CONCLUSIONS: Noncardiac surgery is required frequently after PCI, whereas bleeding is less common. Before implanting a drug-eluting or bare-metal stent, individual patient risk stratification by the interventional cardiologist should include assessment of whether there is an increased likelihood of needing noncardiac surgery or developing bleeding.

A modeling intervention in heart failure.

BACKGROUND: Peak oxygen uptake (VO(2)) testing is commonly used to assess chronic heart failure (CHF) patients' exercise tolerance. The test requires maximal effort; however, many participants have low confidence (self-efficacy) to perform optimally. PURPOSE: This randomized controlled trial examined the effectiveness of a modeling intervention to increase Peak VO(2) (PVO(2)) and self-efficacy in people diagnosed with CHF. METHODS: Twenty participants with a diagnosis of CHF were randomized to either an intervention (modeling DVD) or a control group. Both groups completed a measure of self-efficacy prior to performing two PVO(2) tests, each separated by 7 days. After completing the first test (T1) the intervention group watched a 10-min coping model DVD. All participants returned 1 week later (T2) to complete identical study procedures. RESULTS: Analysis of covariance results showed that compared with the participants in the control group, those assigned to the modeling intervention had higher PVO(2) at T2, F (1, 19) = 4.38, p = 0.05, eta (2) = 0.21 and self-efficacy, F (1, 19) = 5.80, p < 0.05, eta (2) = 0.25. Only partial support was found for change in self-efficacy mediating treatment outcome (PVO(2)). CONCLUSIONS: Watching a modeling video is associated with increased PVO(2) and self-efficacy. These results have implications for testing patients in a clinical setting to maximize exercise tolerance test results.

The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the PRINC (Plavix Response in Coronary Intervention) trial.

OBJECTIVES: This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. BACKGROUND: Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. METHODS: A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. RESULTS: Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01). CONCLUSIONS: In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).

The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial.

OBJECTIVES: This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. BACKGROUND: Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). METHODS: Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. RESULTS: CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). CONCLUSIONS: Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).